IMIM 2019 Trustees

Public Funders

Hospital del Mar Medical Research Institute (IMIM) PRBB Building Dr. Aiguader, 88 08003 Barcelona (Spain) [email protected] www.imim.es

Coordination content Marta Calsina, Rosa Manaut

September 2020 Summary

Introduction ...... 4

An overview of 2019 ...... 6

Scientific Highlights ...... 11 Effectiveness of a new bladder cancer treatment demonstrated ...... 12 PENSA Project: Analysing whether it is possible to slow down cognitive decline . . 14 80% of adult men in Spain will be obese or overweight by the year 2030 . . . . .16 Living in a noisy area increases the risk of suffering a more serious stroke . . . . .18 Our own bodies hold the key to designing safer drugs ...... 20 Mechanism determined for treating the most aggressive tumours ...... 22

Programmes ...... 25 Biomedical Informatics ...... 26 Cancer ...... 42 Epidemiology and Public Health ...... 90 Inflammatory and Cardiovascular Disorders ...... 132 Neurosciences ...... 198

Facts and Figures ...... 239 Core Facilities ...... 240 Internal Services ...... 242 Common Areas and Laboratories ...... 246 Internal and External Services ...... 248 Other Services ...... 256 Research Activity ...... 259 Scientific Publications ...... 260 Research Grants and Transfer of Results ...... 264 Clinical Guidelines ...... 268 Committees ...... 270 Scientific Advisory Board ...... 276 Management ...... 279 Management Structure ...... 280 Income ...... 282 Human Resources ...... 287 Quality ...... 292 Communication ...... 296 Governing Bodies ...... 305 Introduction

Joaquim Bellmunt Jordi Martínez Director IMIM Director IMIM (until August 2019) (from October 2019 to January 2020)

2019 was a year of transition for the management of IMIM. Dr. Joaquim Bellmunt left the position of Director in August, after almost three years, and in early October, Dr. Jordi Martínez temporarily took on the functions of director of the institute until Dr. Joaquin Arribas joined in January 2020. In accordance with the reaccreditation of IMIM as a Healthcare Research Institute at the end of 2018, the Secretary General for Scientific Coordination of the Spanish Ministry of Science, Innovation and Universities also approved changes in the composition of the institute. Thus, in 2019, the foundation BarcelonaBeta Brain Research Center was integrated in the institute and The Genome Regulation Centre (CRG), the Barcelona Global Health Institute (ISGlobal), and the Barcelona Biomedical Research Park Consortium (PRBB), signatories of the Institute’s founding agreement, left the institute. IMIM joined the Catalonia Research Portal (PRC), a portal of the Directorate General for Research of the Catalan government’s Universities and Research Secretariat, which collects, exhibits and disseminates the results of the research produced by Catalan universities and research centers, thus facilitating open access to scientific production. This year saw a greater number of international and EU competitive projects, which has led to a general increase in the institution’s income, among other factors. At the national level, there was a 48% success rate in projects of the Carlos III Institute of Health, a higher percentage than the mean for Spain, which stands at 35%. Also of note was the increase in clinical trials and services contracted for an overall amount of more than 9 million euros.

4 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Introduction

In terms of ISCIII personal grants, the results for 2019 were exceptional: 3 intensifications, 4 post-residency Río Hortega grants, 3 Sara Borrell post-doctoral grants, 5 Pre-doctoral Training Grants in health research (PFIS), 2 Miguel Servet researcher contracts and 2 Juan Rodés Grants. Activity on transfer of results has continued to increase, with 5 European patents submitted, of which 3 are jointly owned with other centers. A total of 919 scientific publications were produced in 2019, of which 748 are original articles and reviews with an impact factor. The “IMIM Open Access Policy” was also approved this year with the aim of promoting the dissemination of scientific production under open access and in accordance with current national and international law. Open access aims to achieve permanent, free and unrestricted access to scientific and academic content with the aim of encouraging visibility, dissemination and socialization of knowledge. The 2018-2021 2nd Equal Opportunities Plan for men and women was approved by the Management Commission and the Board of Governors of the IMIM Foundation in June 2019 and was drafted and agreed by an equality commission made up of equal numbers of male and female representatives of the employees and of the institution. Furthermore, IMIM has signed the letter of commitment to equality in medical research in Catalonia, in the framework of the first Gender in Health Sciences Summit, organized by the Catalan Health Care Quality and Evaluation Agency (AQuAS) and the Department of Health of the Catalan Autonomous Government, in collaboration with the Foundation “la Caixa” with the aim of ending gender inequality in the research system in Catalonia. In 2019, IMIM was mentioned in the media in a total of 2310 news items. The number of impacts was 20% higher than the previous year. Of note was the success of the press release “80% of the adult population in Spain will present obesity or be overweight by the year 2030”, with 411 mentions in the press. From July to November 2019, the Ciutadella-Vila Olímpica metro held the exhibition “Leonardo da Vinci at the PRBB”, organized jointly by all the PRBB centers. The aim of the exhibition was to provide a graphic vision of human biology while commemorating the 500th anniversary of the death of Leonardo da Vinci (1452-1519). The leitmotiv of the exhibit, “from macro to micro”, followed the profile of the research carried out in the PRBB centers, where the different aspects of biomedicine are studied in all areas and at all levels.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 5 An overview of 2019

€

55 21 M€ 719 Research Income Professionals groups

212 748 Research Original articles and reviews projects with IF (59% First quartile) 46 Doctoral Theses Read

28 2,310 Awards Items Recorded in the Media

6 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY An overview of 2019

Programmes 5

Biomedical Cancer Epidemiology and Informatics 12 Groups Public Health 4 Groups 9 Groups 1 Associated 1 Associated

Inflammatory and Neurosciences Cardiovascular Disorders 8 Groups 15 Groups 5 Associated

Personnel 719

Researchers PhD Students Technicians Support 372 59 209 79 51% women 75% women 73% women 81% women 49% men 25% men 27% men 19% men

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 7 An overview of 2019

Current competitive projects by funding institution

National 84.9% (180) Other 7.08% International WADA 2.83% European 15.1% (32) Union 5.19%

Other 18.87% ISCII 40.57%

Generalitat de Catalunya 1.42%

Departament de Salut 7.55%

Agencia Estatal de Investigación 7.08% Fundación Mutua Madrileña 0.47% La Caixa 1.42% COIB 1.42% Ministerio de Sanidad 0.94% AEEC 2.36% La Marató 2.83%

Projects by programme 212

17 43 38 57 53

Biomedical Cancer Epidemiology Inflammatory Neurosciences Informatics and Public and Health Cardiovascular Disorders Other: 4

8 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY An overview of 2019

Publications by programme 919

29 179 258 318 135

Biomedical Cancer Epidemiology Inflammatory Neurosciences Informatics and Public and Health Cardiovascular Disorders

Publications with international collaboration

+ than 50 between 21 between 10 - than 10 and 50 and 20

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 9

Scientific Highlights

> E ffectiveness of a new bladder cancer treatment demonstrated

> P ENSA Project: Analysing whether it is possible to slow down cognitive decline

> 8 0% of adult men in Spain will be obese or overweight by the year 2030

> L iving in a noisy area increases the risk of suffering a more serious stroke

> O ur own bodies hold the key to designing safer drugs

> M echanism determined for treating the most aggressive tumours

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 11 Scientific Highlights

Effectiveness of a new bladder cancer treatment demonstrated

It involves an inhibitor of a dual protein, mTORC1/2, which is key in tumour growth

Researchers from the Molecular Cancer group at the Hospital del Mar Medical Research Institute (IMIM) and doctors from Hospital del Mar, have demonstrated the effectiveness of a drug for treating metastatic bladder cancer in patients who did not respond to the usual treatment. The preliminary results of an ongoing clinical trial show that TAK-228, a mTORC1/2 protein inhibitor, can stop the progression of the disease. The principle behind this drug is the inhibition of the mTORC1/2 protein, commonly present in tumours. This protein plays a key role in the development and spread of tumours. The researchers analysed its effectiveness in the laboratory, in bladder cancer cell lines both in vitro and implanted into mice. They also worked with fresh tissue from the tumours of patients. The novelty is that, at the same time, they designed a clinical trial that is now underway. The results, published in Molecular Cancer Research, demonstrate not only the good preclinical results of this drug, but that these are even better when combined with other treatments. At the same time, the researchers determined that it was more effective on a subgroup of tumours with particular characteristics, certain genetic alterations that could be used as therapeutic targets”, explain the researchers.

Good results in patients

The clinical trial, which evaluated seven patients, reports that four of these showed a positive response to the drug. In these sufferers, tumour growth was slowed and tumour progression avoided. These were metastatic bladder cancer patients who did not respond to the usual treatments, including immunotherapy. Currently in the United States, only one treatment for a bladder cancer molecular target has been approved. It is a unique treatment, differing from chemotherapy or

12 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

radiation therapy. Dr. Bellmunt highlights this fact, pointing out that. This studied drug could become a second potential therapeutic target in bladder cancer patients. It is not chemotherapy, radiotherapy, or immunotherapy, but it attacks specific genetic alterations found in tumours.

Reference article

Hernández A, Rodríguez-Vida A, Juanpere N, Arpí O, Menéndez S, Soria-Jiménez L, Martínez-Fernández A, Iarchouk N, Rojo F, Albanell J, Brake R, Rovira A, Bellmunt J. Novel oral mTORC1/2 inhibitor TAK-228 has synergistic antitumor effects when combined with paclitaxel or PI3Kα inhibitor TAK-117 in preclinical bladder cancer models. Mol Canc Res 2019; 17(9): 1931-1944.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 13 Scientific Highlights

PENSA Project: Analysing whether it is possible to slow down cognitive decline

The project will involve 200 participants with subjective memory complaint, a phase preceding cognitive deterioration

Researchers at the Hospital del Mar Medical Research Institute (IMIM) and the Barcelonaβeta Brain Research Center (BBRC), have started recruiting participants for the PENSA Study (Prevention of cognitive decline in ApoE4 carriers with Subjective Cognitive Decline after EGCG and a multimodal intervention). This is a clinical trial in prevention that will monitor, over the course of one year, 200 people who present with memory complaints, a stage that may precede Alzheimer’s disease. The aim of the study is to check the evolution of participants and the impact on them of a programme of multimodal intervention in lifestyles and the taking of a dietary supplement, epigallocatechin gallate (EGCG), a natural compound from green tea. In previous studies, this component has shown positive effects on the cognitive function of people with Down Syndrome, in combination with a cognitive stimulation programme. The participants will be divided into four groups. They will receive EGCG or placebo and, in addition, two of the groups will receive lifestyle recommendations while the other two groups will participate in an intensive programme of lifestyle changes that includes diet, physical activity and cognitive stimulation.

Personalised monitoring

The researchers will carry out personalised monitoring and control of the participants. In the first phase, they will carry out monitoring of participants’ lifestyles to ascertain their starting point. Their physical activity will be controlled via an activity bracelet and so will their dietary habits. Then, they will be given targets, in terms of diet and physical activity, as well as a cognitive stimulation programme. An app has been designed for smartphones that will enable the monitoring of diet, physical activity, social interaction, and mood continually during the entire intervention. The app enables individualised monitoring of compliance with the

14 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

intervention and adapts the demandingness of the challenges posed in a personalised way while favouring and reinforcing the connection with participants thanks to the sending of SMS messages. The intervention includes assistance once per week at the gym, nutritional monitoring, activities for strengthening cognitive stimulation and psychoeducational support. The aim of the project is to check whether these interventions serve to improve the cognitive function of these individuals before the appearance of the first symptoms of Alzheimer’s. The researchers are advocating prevention studies, because they know that one out of every three cases is attributable to modifiable risk factors. The study was presented at a symposium of the worldwide initiative World Wide FINGERS, which works to promote projects for primary prevention of cognitive deterioration and dementia. PENSA forms part of this international consortium and is funded with 1 million dollars by the Alzheimer’s Association of the United States. In the design of the activities proposal for the different interventions prepared for improving participant lifestyle habits, there was involvement, for the first time, of a focus group of 9 people, three of whom came from the Hospital del Mar Patients Forum. Incorporating the opinion and encouraging the participation of patients in the first phase of the project, is an innovative initiative that enables improvement of the different activities programmed to achieve the desired goal.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 15 Scientific Highlights

80% of adult men in Spain will be obese or overweight by the year 2030

In the case of adult women, this figure will reach 55% of the total of the population

A study led by researchers at the Hospital del Mar Medical Research Institute (IMIM) and doctors from the Hospital del Mar, has calculated as almost 2 billion euros the excess cost for the State’s health system caused by attending people with overweight, obesity and morbid obesity. This is the most updated revision available, based on around fifty articles published previously. The articles reviewed, which analyse data from over 300,000 people, have enabled researchers to carry out monitoring of the evolution of the prevalence of overweight and obesity in Spain between the years 1987 and 2014. Based on these results estimates have been made for the years 2006, 2016 and 2030. According to the study, in the year 2016 in Spain there were some 24 million cases of excess weight, in other words, 70% of men and half of women of adult age. These represent 3 million people more than a decade before. If this tendency is maintained, the researchers envisage that the figure will exceed 27 million people by the year 2030, affecting 80% of adult men and 55% of adult women in this age group. It has been estimated that between the years 1987 and 2014, an annual increase occurred of 0.28% in overweight in men and 0.10% in women, and of obesity of 0.50% in men and 0.25% in women.

Excess costs of excess weight

Analysis of the data has also enabled an estimate to be made of the extra cost that caring for people with excess weight will represent for the health system. The researchers explain that “These are people who have greater possibilities of increasing health spending due to the comorbidities that they suffer, such as cardiovascular disease, diabetes or cancer, all associated with overweight and obesity”. Thus, according to the estimates of researchers, in the year 2016 the direct excess cost with respect to 2006 increased by 524 million euros to reach 1,950 million. And if the increase in cases is maintained, it will continue to grow by 440 million euros per year, to exceed 3 billion euros by the year 2030.

16 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

Benefits of acting

Researchers point to various reasons for the sustained growth in overweight in Spain. Less healthy food patterns, with a greater consumption of industrial products and a reduction in fruit, vegetables and legumes, more sedentary lifestyles and an increase in employment and purchasing power during the period studied, which may lead to people acquiring less traditional dietary patterns. To break with this tendency, they advocate interventions at different levels, such as new taxes on less healthy foods and protection of those that are ingredients in healthy diets, and educational policies to promote healthy habits, such as regular exercise starting at school. It would also be necessary to advance in new pharmacological strategies when necessary. They point out that obesity prevention plans could have a strong impact and be very cost-effective.

Reference article

Barroso M, Goday A, Ramos R, Marín-Ibáñez A, Guembe MJ, Rigo F, Tormo-Díaz MJ, Moreno-Iribas C, Cabré JJ, Segura A, Baena-Díez JM, Gómez de la Cámara A, Lapetra J, Quesada M, Medrano MJ, Berjón J, Frontera G, Gavrila D, Barricarte A, Basora J, García JM, García-Lareo M, Lora-Pablos D, Mayoral E, Grau M, Marrugat J, FRESCO Investigators. Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality. Prev Med 2018; 107: 81-89.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 17 Scientific Highlights

Living in a noisy area increases the risk of suffering a more serious stroke

Exposure to high levels of traffic noise increases the risk of suffering a more serious ischemic stroke by 30%

The high levels of environmental noise we are subjected to in large cities can increase both the severity and the consequences of an ischaemic stroke. More precisely, researchers calculate the increased risk at 30% for people living in noisier areas. In contrast, living close to green areas brings this risk down by up to 25%. This is the first time that these factors have been analysed in relation to stroke severity. The study has been published in the journal Environmental Research. The researchers looked at the influence of noise levels, air pollution (particularly suspended particles smaller than 2.5 microns; PM2.5), and exposure to green areas on nearly 3,000 ischaemic stroke patients treated at Hospital del Mar between 2005 and 2014. To do this, they used data from the Cartographic Institute of Catalonia, as well as models to analyse atmospheric pollutant levels, the noise map of Barcelona, and satellite images to define areas with vegetation. They also took into account the socioeconomic level of the locality where the patients lived. The study gives us initial insight into how noise levels and exposure to green spaces influences the severity of ischaemic stroke. “We have observed a gradient: the more green spaces, the less serious the stroke. And the more noise, the more serious it is. This suggests that factors other than those traditionally associated with stroke may play an independent role in the condition”, researchers explain. Exposure to green spaces can benefit human health through various mechanisms. For example, it can reduce stress, encourage social interaction, and increase levels of physical activity.

More noise, greater stroke severity

Previous studies have demonstrated that living in places with high levels of air pollution or noise, or with fewer green areas, exposes the population to a higher risk of suffering an ischaemic stroke. This work broadens our knowledge in this field, showing that the place where we live affects not only the risk of suffering a stroke, but also its severity if one occurs. In this sense, the results indicate that patients living in noisier areas

18 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

presented more severe strokes on arrival at hospital. The researchers have analysed the effects of stroke on neurological deficits, such as speech impairment and mobility, using the NIHSS (National Institute of Health Stroke Scale). The researchers did not aim to determine which noise levels lead to increased risk, but rather to detect a gradient by comparing patients living in noisier areas with those living in quieter areas. Indeed, the World Health Organisation (WHO) recommends traffic noise limits of a maximum of 53 decibels during the day and 45 decibels at night. “The average noise level to which patients have been exposed, as well as the general population of the study area, requires reflection, as it is considerably above the WHO recommendations”, point out the researchers. The same researchers have already revealed that high levels of air pollution from diesel engines increase the risk of suffering atherothrombotic stroke by 20%.

Reference article

Rosa Maria Vivanco-Hidalgo, Carla Avellaneda-Gómez, Payam Dadvand, Marta Cirach, Ángel Ois, Alejandra Gómez González, Ana Rodríguez-Campello, Pablo de Ceballos, Xavier Basagaña, Ana Zabalza, Elisa Cuadrado-Godia, Jordi Sunyer, Jaume Roquer, Gregory A. Wellenius. Association of residential air pollution, noise, and greenspace with initial ischemic stroke severity. Environ Res 2019; 179(Part A): 108725.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 19 Scientific Highlights

Our own bodies hold the key to designing safer drugs

It’s the first time that the affinities of endogenous ligands and drugs for the same proteins have been quantified

Based on a study of 566 drugs that interact with 129 different proteins, researchers from the Systems Pharmacology research group, part of the Research Programme on Biomedical Informatics (GRIB) (IMIM-UPF) in collaboration with researchers from the University of New Mexico, in the United States, realised that 71% of drugs have stronger affinities for their target proteins than those of the small internal molecules responsible for regulating their functions. Surprisingly, this is the first time that the affinities of endogenous ligands and drugs for the same proteins have been quantified. Humans have thousands of proteins, each with a specific function that is often regulated by thousands of small molecules synthesised by our bodies. This set of small molecules, also known as “endogenous metabolites”, is known as the “human metabolome”. Each one interacts with its native protein with a certain affinity that has been carefully optimised, in a natural way, throughout the long process of evolution, and this can vary between species and even in some instances, more subtly, between individuals. Most pharmaceuticals are small synthetic molecules that exert their therapeutic action through optimal interaction with one or more proteins whose function is regulated by one of our small internal molecules. “To date, no one had ever considered the idea that a drug’s minimum interaction with its target protein should be similar to the affinity shown by the body’s own small molecule. We have discovered that our own molecules, naturally optimised by evolution, provide the frame of reference necessary for efficiently designing more effective and safer drugs”, explain the researchers. More than 90% of candidate drug molecules fail to pass the preclinical phase (tests using cells, tissues, and animals) or the clinical phase (tests on people) due to efficacy or toxicity problems, and this percentage has not dropped significantly over the last decade. “Incorporating the affinity of endogenous molecules for their native proteins as a reference threshold in the preclinical drug design phase would have an important

20 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

impact on improving the efficiency of the optimisation process, reducing animal testing and the associated financial costs. It would also allow an initial estimate of the molecule’s safety margins, and potentially reduce the risk of the drug failing in the clinical phase due to translational problems between species”, conclude the resarchers. The study was published in the prestigious journal Drug Discovery Today, which also dedicated the Editorial to it, and it has been reviewed by Nature Reviews Drug Discovery.

Reference article

Article: Bofill A, Jalencas X, Oprea TI, Mestres J.The human endogenous metabolome as a pharmacology baseline for drug discovery. Drug Discov Today 2019, 24(9), 1806- 1820. Editorial Review

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 21 Scientific Highlights

Mechanism determined for treating the most aggressive tumours

This is a key factor in treatment resistance and tumour spread

A study led by researchers from the Hospital del Mar Medical Research Institute (IMIM), has determined, for the first time, the importance of a cell mechanism that may be key to treating metastatic tumours. The work has demonstrated the role a protein, kinase IKKα, plays in the ability of tumour cells to repair themselves. This is a key factor in treatment resistance and tumour spread. The research has been published in the journal Molecular Cell. The researchers analysed the role of this protein, activated by mutations of the BRAF and KRAS oncogenes, present in the majority of the most aggressive tumours. The function of this protein is to facilitate DNA-repair in tumour cells after they have been damaged by chemotherapy, making them more resistant to the action of these drugs. This is key for the treatment approach, since this new study demonstrates, conclusively, that combining a BRAF oncogene inhibitor with chemotherapy deactivates and kills the tumour. These same oncogenes, in addition to converting normal cells into tumours, make them better able to repair the damage caused by chemotherapy agents or radiation, and make them more resistant. In other words, they play a double role, facilitating tumour transformation and protecting the tumour from the damage caused by chemotherapy and radiation. “The presence of these mutations makes treatment very difficult but this is also an advantage, because if, thanks to these mutations, the tumour cell is more resistant to damage, eliminating their activity with drugs that are currently used in clinical practice will make the tumour even more sensitive to the treatments. And that’s what we’ve demonstrated” explain the researchers.

Analysis with tumours from human patients

The researchers verified the role of the protein IKKα and its importance as a therapeutic target, implanting colon tumours, from human patients who had developed metastasis and treatment resistance, into mice. The study results showed that animals

22 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Scientific Highlights

which received no treatment, or were treated only with either BRAF inhibitors or chemotherapy, died. But those that received a treatment combining these inhibitors with chemotherapy survived. What is more, the tumour cells were found to have died. This was confirmed with in vitro samples. The researchers behind the study now want to start a clinical trial in cancer patients, taking advantage of the fact that the drugs employed in the study already exist and are used in clinical practice. Firstly, their usefulness for treating colon and rectal cancer will be analysed, but the researchers have not ruled out the possibility that they may be effective for any kind of tumour involving BRAF and KRAS oncogenes, such as pancreatic cancer and melanoma.

Reference article

Carlota Colomer, Pol Margalef, Alberto Villanueva, Anna Vert, Irene Pecharroman, Laura Solé, Mónica González-Farré, Josune Alonso, Clara Montagut, Maria Martínez-Iniesta, Joan Bertran, Eva Borràs, Mar Iglesias, Eduard Sabidó, Anna Bigas, Simon J. Boulton & Lluís Espinosa. IKKα kinase regulates the DNA damage response and drives chemoresistance in Cancer. Mol Cell 2019; 75(4): 669-682.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 23

Programmes

> Biomedical Informatics

> Cancer

> Epidemiology and Public Health

> Inflammatory and Cardiovascular Disorders

> Neurosciences

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 25 Programmes

Biomedical Informatics

5 27 17 29 Research Professionals Research Publications groups projects

Programme Director Ferran Sanz

RESEARCH GROUPS ASSOCIATED GROUPS

Evolutionary Genomics Pharmacoinformatics Maria del Mar Albà Manuel Pastor

GPCR Drug Discovery Jana Selent

Integrative Biomedical Informatics Laura Inés Furlong and Ferran Sanz

Systems Pharmacology Jordi Mestres

26 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics Programme

The mission of the joint Research Programme on Biomedical Informatics (GRIB) of IMIM and the Pompeu Fabra University (UPF) is to develop and apply computational methods and information technologies for a better understanding and prediction of biological phenomena, placing special emphasis on those related to human diseases, their diagnosis and pharmacological treatment. GRIB has five research groups affiliated to IMIM: Evolutionary Genomics (M. Albà), GPCR Drug Discovery (J. Selent), Integrative Biomedical Informatics (L. Furlong and F. Sanz), PharmacoInformatics (M. Pastor) and Systems Pharmacology (J. Mestres).

Outstanding scientific achievements

During 2019, GRIB coordinated two EU-funded projects, eTRANSAFE and NEURON PSYBIAS, and participated as a partner in seven more projects: FAIRplus, TransQST, EU- ToxRisk, Escape-net, EOSC-Life, EU-OPENSCREEN DRIVE and EXCELERATE, as well as other national projects and contracts with the industry. GRIB’s research activities led to the creation of the spin-off company MedBioinformatics Solutions, which develops products and services based on DisGeNET, an internationally recognised knowledge resource on disease genetics (50,000+ users per year). Mar Albà’s research on de novo genes was featured in Nature on Oct 16, 2019.

Some scientific publications

• IMEx Consortium Curators at al. (incl. Piñero J & Furlong LI). Capturing variation impact on molecular interactions in the IMEx Consortium mutations data set. Nat Commun 2019; 2; 10(1): 10. • Ruiz-Orera J, Albà MM. Translation of Small Open Reading Frames: Roles in Regulation and Evolutionary Innovation. Trends Genet. 2019; 35(3): 186-98. • Bofill A, Jalencas X, Oprea TI, Mestres J. The human endogenous metabolome as a pharmacology baseline for drug discovery. Drug Discov Today 2019; 24(9): 1806-20. (Drug Discovery Today included an Editorial on this paper and Nature Reviews Drug Discovery commented it). • Leis A, Ronzano F, Mayer MA, Furlong LI, Sanz F. Detecting Signs of Depression in Tweets in Spanish: Behavioral and Linguistic Analysis. J Med Internet Res 2019; 21(6): e14199.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 27 Evolutionary Genomics

> Biomedical Informatics RESEARCH GROUP

Group Leader Members Maria del Mar Albà Soler William Robert Blevins (Technician) (ICREA Professor) José Carlos Montañés Domínguez (Technician) [email protected] Simone Moro (Technician)

The Evolutionary Genomics group, led by Mar Albà, uses comparative genomics and large-scale transcriptomics data to understand the complexity of gene regulation and evolutionary innovation processes. We are developing novel approaches to reconstruct and quantify the transcriptome using high-throughput RNA sequencing data, including long-read technologies such as Nanopore. We are also using techniques for sequencing ribosome-protected RNA fragments, also known as ribosome profiling. Using these techniques we have been able to discover many novel translated small ORFs (sORFs). Some of these sORFs correspond to highly conserved small proteins, or micropeptides, that can have important cellular functions. Others are intermediates in the process of generation of de novo genes, new types of gene that arise from previously non-coding parts of the genome. Finally, we are also using transcriptomics data to study the emergence of novel transcripts and neoantigens in cancer.

28 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics Evolutionary Genomics

Main Publications

• Ruiz-Orera J, Albà MM. Translation of Small Open Reading Frames: Roles in Regulation and Evolutionary Innovation. Trends Genet 2019; 35(3): 186-198. IF 10.627. D1. • Blevins WR, Tavella T, Moro SG, Blasco-Moreno B, Closa-Mosquera A, Díez J, Carey LB, Albà MM. Extensive post-transcriptional buffering of gene expression in the response to severe oxidative stress in baker’s yeast. Sci Rep 2019; 9: 11005. IF 4.011. Q1. • Blevins WR, Carey LB, Albà MM. Transcriptomics data of 11 species of yeast identically grown in rich media and oxidative stress conditions. BMC Res Notes 2019; 12: 250. SJR 0.661. Q2. • Ruiz-Orera J, Albà MM. Conserved regions in long non-coding RNAs contain abundant translation and protein–RNA interaction signatures. NAR Genomics and Bioinformatics 2019; 1(1): e2. See all Publications

Ongoing Research Projects

• Mecanismos de formación de genes nuevos - Financing institution: Ministerio de Economía y Competitividad (BFU2015- 65235-P) - Period: from 2016 to 2019 - Principal investigator: Albà Soler, Maria del Mar See all Projects

Appointments

• Maria del Mar Albà Soler. Member of the jury of Premi Ciutat de Barcelona Ciències de la Vida. Barcelona, 10-20 January 2019. • Maria del Mar Albà Soler. Member of the jury of Fitch Prize Annual Meeting Society for Molecular Biology and Evolution. SMBE’19. Manchester, UK, 23 July 2019.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• William Robert Blevins. Pint of Science: Dur la recerca científica als bars. 13 September 2019. • William Robert Blevins; José Luis Villanueva-Cañas. Pint of Science: Beyond Jurassic Park. Frontiers of Science and Science Fiction. BlackLab (Barcelona), 22 May 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 29 GPCR Drug Discovery

> Biomedical Informatics RESEARCH GROUP

Group Leader Members Jana Selent Tomek Stepniewski (PhD Student) [email protected]

The group is focused on the functionality of G-protein-coupled receptors (GPCRs) in the context of CNS-related disorders, taking into account: receptor plasticity, activation mechanism, signalling bias, ligand binding, the effect of the membrane and other interaction partners. The ultimate goal is to translate the molecular insights obtained into the design of drug candidates with improved therapeutic profiles. The main research lines are: • In-silico Multi-Receptor Profiling of Antipsychotic Drugs. We study the molecular mechanisms of current antipsychotic drugs that are responsible for their clinical efficacies. • GPCR Dimers as a Drug Target for the Treatment of Schizophrenia. Our group provides support for the design of bivalent ligands that selectively target a specific GPCR dimer. Once a target is validated, we apply diverse computational tools to obtain first small drug-like molecules towards this target. • Membrane Lipid-Mediated Effects on GPCR signalling by studying direct and indirect membrane effects on receptor monomers and dimers using all-atom as well as coarse- grained simulation setups. • Database for GPCR dynamics. The main mission of this project is to provide dynamic insights into crystallized receptors at a publicly accessible platform.

30 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics GPCR Drug Discovery

Main Publications

• Ghosh E, Dwivedi H, Baidya M, Srivastava A, Kumari P, Stepniewski T, Kim HR, Lee MH, van Gastel J, Chaturvedi M, Roy D, Pandey S, Maharana J, Guixà-González R, Luttrell LM, Chung KY, Dutta S, Selent J, Shukla AK. Conformational Sensors and Domain Swapping Reveal Structural and Functional Differences between β-Arrestin Isoforms. Cell Rep 2019; 28(13): 3287-3299.e6. IF 7.815. Q1. • Sánchez-Melgar A, Albasanz JL, Guixà-González R, Saleh N, Selent J, Martín M. The antioxidant resveratrol acts as a non-selective adenosine receptor agonist. Free Radical Biol Med 2019; 135: 261-273. IF 5.657. Q1. • Abraham MJ, Apostolov RP, Barnoud J, Bauer P, Blau C, Bonvin AMJJ, Chavent M, Chodera JD, Condic-Jurkic K, Delemotte L, Grubmüller H, Howard RJ, Jordan EJ, Lindal E, Ollila OHS, Selent J, Smith DGA, Stansfeld PJ, Tiemann JKS, Trellet M, Woods CJ, Zhmurov A. Sharing Data from Molecular Simulations. J Chem Inf Model. 2019; 59(10): 4093-4099. IF 3.966. Q1. See all Publications

Ongoing Research Projects

• A novel paradigm for effective and safer treatment of schizophrenia: biased (ant) agonists with a characterized polypharmacological profile - Financing institution: ERA-Net NEURON – European Commission / ISCIII - Period: from 2018 to 2021 - Principal investigator: Selent, Jana • Disección de los fundamentos de la eficacia superior de la clozapina para el tratamiento de la esquizofrenia: desde pruebas moleculares hasta evidencias cerebrales - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00094) - Period: from 2018 to 2021 - Principal investigator: Selent, Jana • La modulación alostérica del receptor D2 de la dopamina forma parte del mecanismo de acción del litio: de la evidencia molecular a la neuroimagen funcional - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00460) - Period: from 2016 to 2020 - Principal investigator: Selent, Jana See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 31 Biomedical Informatics GPCR Drug Discovery

Participation in Research Networks • European Research Network on Signal Transduction (ERNEST) - Financing institution: European Commission - Period: from 2019 to 2023 - Vice chair: Selent, Jana

32 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Integrative Biomedical Informatics

> Biomedical Informatics RESEARCH GROUP

Group Leader Group Leader Laura Inés Furlong Nespolo Ferran Sanz Carreras

[email protected] [email protected]

Members

Eduardo Eyras Jiménez (Researcher) Alexia Giannoula (Researcher) Miguel Ángel Mayer Pujadas (Researcher) Janet Piñero González (Researcher) Juan Manuel Ramírez Anguita (Researcher) Gabriel Santpere Baró (Researcher) Judith Pérez Granado (PhD Student) Emre Güney (Technician) María de los Ángeles Leis Machín (Technician) Francesco Ronzano (Technician) Josep Saüch Pitarch (Technician) María Jesús Donlo Fernández (Research Assistant) Alfons González Pauner (Research Assistant) Carina Oliver Dutrem (Research Assistant)

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 33 Biomedical Informatics Integrative Biomedical Informatics

The huge wealth of biomedical information that is currently available is underused because of the difficulties in seeking, integrating and analyzing the relevant information. There is also considerable great difficulty involved in identifying and using clinically actionable information. The goal of the Integrative Biomedical Informatics (IBI) group is to develop computational methods and tools to address these challenges, with the aim of better understanding human health and disease and contributing to the design of more effective and safer therapeutic interventions. The ongoing research areas of the IBI group are the following: • Text mining • Knowledge management and linked data • Real World Data (RWD) analytics in health • Systems biology and network medicine for the study of human diseases and drug toxicity • Integrative knowledge management and exploitation in drug discovery and development

Main Publications

• Leis A, Ronzano F, Mayer MA, Furlong LI, Sanz F. Detecting Signs of Depression in Tweets in Spanish: Behavioral and Linguistic Analysis. J Med Internet Res 2019; 21(6): e14199. IF 4.945. D1. • Ronzano F, Gutiérrez-Sacristán A, Furlong LI. Comorbidity4j: a tool for interactive analysis of disease comorbidities over large patient datasets. Bioinformatics 2019; 35 (18): 3530-3532. IF 4.531. Q1. • Pérez-Granado J, Piñero J, Furlong LI. ResMarkerDB: a database of biomarkers of response to antibody therapy in breast and colorectal cancer. Database (Oxford) 2019; 2019: baz060. IF 3.683. Q1. See all Publications

Ongoing Research Projects

• FAIRplus - Financing institution: Innovative Medicines Initiative – IMI (802750) - Period: from 2019 to 2021 - Principal investigator: Sanz Carreras, Ferran

34 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics Integrative Biomedical Informatics

• Enhancing TRANslational SAFEty Assessment through Integrative Knowledge Management (eTRANSAFE) - Financing institution: Innovative Medicines Initiative – IMI (777365) - Period: from 2017 to 2022 - Principal investigator: Sanz Carreras, Ferran • Translational quantitative systems toxicology to improve the understanding of the safety of medicines (TransQST) - Financing institution: Innovative Medicines Initiative – IMI (116030) - Period: from 2017 to 2021 - Principal investigator: Sanz Carreras, Ferran • Clinical Knowledge Aggregation by Mining medical rEports (CliKA-MinE) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00230) - Period: from 2018 to 2020 - Principal investigator: Furlong Nespolo, Laura Inés • EXCELLERATE: Fast-track ELIXIR implementation and drive early user exploitation across the life-sciences - Financing institution: European Commission H2020 (676559) - Period: from 2015 to 2019 - Principal investigator: Sanz Carreras, Ferran See all Projects

Participation in Research Networks

• Plataforma Tecnológica Española de Medicamentos Innovadores (PTEMI) - Period: from 2006 - Principal investigator: Sanz Carreras, Ferran; co-president of the platform • Bioinformatics Barcelona Association (BIB) - Period: from 2015 - Principal investigator: Sanz Carreras, Ferran; vice-president • Spanish Institute of Bioinformatics (INB) - Period: from 2005 - Principal investigator: Sanz Carreras, Ferran; PI of the node for Biomedical Informatics

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 35 Systems Pharmacology

> Biomedical Informatics RESEARCH GROUP

Group Leader Members Jordi Mestres López Andreu Bofill Pumarola (PhD Student) [email protected] Emilio Centeno Ortiz (Technician) María José Falguera Mata (Technician)

The Research Group on Systems Pharmacology conducts research at the interface between chemistry, biology and informatics to develop novel computational methods that contribute to designing safer, more efficacious, drugs. In this respect, the group is actively involved in several initiatives to explore the mechanisms of action leading to severe adverse drug reactions, with special emphasis on cardiotoxicity and hepatotoxicity, and to investigate the impact of the human endogenous metabolome on the efficacy and safety of drugs. Current efforts are focused on ultimately gaining a better understanding of drug polypharmacology within the context of biological systems as a means of advancing towards precision medicine. The group is also the seed of the biotech company Chemotargets SL, founded in 2006 and currently employing 12 people, seven of whom are former PhD students or postdoctoral researchers of the group. The company develops and markets the CLARITY® intelligence and discovery platform for large-scale prediction of the pharmacology, safety, and diseases of small-molecule pharmaceuticals and cosmeceuticals, currently in use worldwide by 21 big pharma, small and medium biotech companies, academic centers, and not-for-profit organizations, such as the FDA.

36 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics Systems Pharmacology

Main Publications

• Bofill A, Jalencas X, Oprea TI, Mestres J. The human endogenous metabolome as a pharmacology baseline for drug discovery. Drug Discov Today 2019; 24(9): 1806- 1820. (Highlighted in the Editorial of the same issue in Drug Discovery Today 2019 and in Nature Reviews Drug Discovery 2019). IF 6.88. D1. • Olivés J, Mestres J. Closing the Gap between Therapeutic Use and Mode of Action in Remedial Herbs. Front Pharmacol 2019; 10: 1132. IF 3.845. Q1. • Dyballa S, Miñana R, Rubio-Brotons M, Cornet C, Pederzani T, Escaramis G, Garcia- Serna R, Mestres J, Terriente J (2019). Comparison of Zebrafish Larvae and hiPSC Cardiomyocites for Predicting Drug-Induced Cardiotoxicity in Humans. Toxicol Sci 2019; 171(2): 283-295. IF 3.564. Q1. • Vogt I, Mestres J. Information Loss in Network Pharmacology. Mol Inf 2019; 38(7):e1900032. (Journal cover of Volume 38, Issue 7, July 2019). IF 2.375. Q1. • Brennecke P, Rasina D, Aubi O, Herzog K, Landskron J, Cautain B, Vicente F, Quintana J, Mestres J, Stechmann B, Ellinger B, Brea J, Kolanowski JL, Pilarski R, Orzaez M, Pineda-Lucena A, Laraia L, Nami F, Zielenkiewicz P, Paruch K, Hansen E, von Kries J, Neuenschwander M, Specker E, Bartunek P, Simova S, Lesnikowski Z, Krauss S, Lehtiö L, Bilitewski U, Brönstrup M, Taskén K, Jirgensons A, Lickert H, Clausen MH, Andersen JH, Vicent MJ, Genilloud O, Martínez A, Nazaré M, Fecke W, Gribbon P. EU- OPENSCREEN: A Novel Collaborative Approach to Facilitate Chemical Biology. SLAS Discov 2019; 24(3): 398-413. IF 2.192. Q3. See all Publications

Ongoing Research Projects

• EOSC-Life: Providing an Open Collaborative Space for Digital Biology in Europe - Financing institution: European Commission (INFRAEOSC-04-2018) - Period: from 2019 to 2022 - Principal investigator at IMIM: Mestres López, Jordi • EU-OPENSCREEN DRIVE: Ensuring Long-Term Sustainability of Excellence in Chemical Biology within Europe and Beyond - Financing institution: European Commission (INFRADEV-03-2018-2019) - Period: from 2019 to 2022 - Principal investigator at IMIM: Mestres López, Jordi • The impact of the endogenous metabolome on the pharmacology and safety of exogenous small molecules - Financing institution: Ministerio de Economía y Competitividad - Period: from 2018 to 2020 - Principal investigator: Mestres López, Jordi

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 37 Biomedical Informatics Systems Pharmacology

• ESCAPE-NET: European sudden cardiac arrest network: towards prevention, education and new treatment - Financing institution: European Commission (H2020) - Period: from 2017 to 2021 - Principal investigator at IMIM: Mestres López, Jordi See all Projects

Theses

• Szabo V. Polypharmacy in the elderly: data, models and strategies. Universitat Pompeu Fabra - Director: Mestres López, Jordi - Date of defense: 13/03/2019

Appointments

• Jordi Mestres. Member of the Scientific Advisory Board, ChemBioFrance. October 2019.

Outreach

Conferences, Seminars and Courses

• Jordi Mestres. Invited Conference. A structure-based machine-learning approach to design ligands for new emerging and difficult targets. Chem-Bio Informatics Society Annual Meeting. Tokyo, Japan, 21-25 October 2019. • Jordi Mestres. Invited Conference. Why do drugs have the affinities they have? Drug Discovery: Current Trends and Future Prospects. Tucson (AZ), USA, 21-24 February 2019.

38 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics Systems Pharmacology

PharmacoInformatics

> Biomedical Informatics ASSOCIATED GROUP

Group Leader Members Manuel Pastor Maeso Núria Boada Centeno (Researcher) [email protected]

The PharmacoInformatics research group is devoted to the development and application of computational methodologies in the area of drug design and development. Nowadays, computational methodologies are widely applied in many steps of drug discovery and development; from the structural modeling of a pharmacological target to the prediction of the ligand binding affinity. However, in the vast majority of cases the limitations of current technology allow us only to obtain approximate representations of the complex biological phenomena that are the focus of interest in the development of new drugs. The PharmacoInformatics group aims to improve the current state-of-the-art. We develop tools aimed at improving the efficiency of the pharmaceutical R&D process and apply them to the building of predictive models. We try to avoid reductionist approaches and develop multi-scale methods, depicting richer and more realistic representations of the phenomena under study than those produced by classical computational methods.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 39 Biomedical Informatics PharmacoInformatics

Main Publications with IMIM

• Escher SE, Kamp H, Bennekou SH, Bitsch A, Fisher C, Graepel R, Hengstler JG, Herzler M, Knight D, Leist M, Norinder U, Ouédraogo G, Pastor M, Stuard S, White A, Zdrazil B, van de Water B, Kroese D. Towards grouping concepts based on new approach methodologies in chemical hazard assessment: the read-across approach of the EU-ToxRisk project. Arch Toxicol, 2019; 93(12): 3643-3667. IF 5.741. Q1.

MORE INFO

40 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Biomedical Informatics PharmacoInformatics Programmes

Cancer

12 158 43 179 Research Professionals Research Publications groups projects

Programme Director Joan Albanell Mestres

RESEARCH GROUPS Molecular Mechanisms of Cancer and Stemness Lluís Espinosa Applied Clinical Research in Hematological Malignances Poly (ADP-ribose) Polymerases Antonio Salar José Yélamos

Colorectal Neoplasms Clinical and Translational Radiation Oncology Research Manuel Ignacio Algara Xavier Bessa Stem Cells and Cancer Gastroesophageal Carcinogenesis Anna Bigas Manuel Ramón Pera Translational Research on Hematological Genitourinary Cancer Neoplasms Josep Lloreta Blanca Espinet

Localised Hyperthermia Therapies Fernado Burdío

Mechanisms of Tumorigenesis and Tumor Progression Antonio García de Herreros

Molecular Cancer Therapeutics Joan Albanell

42 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Programme

The programme includes basic, preclinical and clinical groups. Group leaders include basic scientists, digestologists, hematologists, immunologists, medical oncologists, radiation oncologists, pathologists, and surgeons, resulting in a multidisciplinary programme that allows undertaking collaborative projects focused on clinically relevant questions. An important line of research is the role of liquid biopsy in the efficacy of targeted drugs in colorectal cancer, culminating in the design of two clinical trials (1) to establish the value of specific mutations for selecting metastatic colorectal cancer patients for individualized therapy (CITRIC trial) and (2) to use ctDNA to individualize adjuvant chemotherapy in early colorectal cancer (PEGASUS trial). In colorectal cancer, the role of IKKalpha kinase and Braf have been further elucidated, emerging as a novel combinatorial therapeutic strategy. We have also collaborated with immunology groups and reported a significant predictive role of both tumour and circulating natural killer cells in predicting the response to anti-HER2 monoclonal antibodies in breast cancer. In the context of a collaborative AECC project, this finding supported an innovative clinical trial on cellular therapy with NKs for patients with HER2+ breast cancer progressing to standard treatment. In bladder cancer, a preclinical study on paclitaxel and mTOR inhibitors provided the foundation for a planned clinical trial. Studies in haematological patients, in collaboration with cardiologists, have provided useful information on parameters of cardiological toxicities that have been incorporated into patient management. Surgical groups have shown the potential of tumour ablation by radiofrequency in pancreatic cancer. From a preclinical perspective there have been also important contributions in both haematological and solid tumours. Collectively, the programme has published 139 papers, 24% in the first decile, and 35% led by programme investigators. A Miguel Servet researcher was awarded by Worldwide Cancer Research for a project on “Hysteresis conveys the EMT spread to neighbouring tumour cells and metastasis”. The phase I clinical trial programme has continued to grow in haematology and oncology.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 43 Cancer Programme

Applied Clinical Research in Hematological Malignances

> Cancer RESEARCH GROUP

Group Leader Members Antonio Salar Silvestre Eugenia Abella Monreal (Researcher) [email protected] Beatriz Bellosillo Paricio (Researcher) Eva Gimeno Vázquez (Researcher) Carmen Jiménez Martínez (Researcher) Blanca Sánchez González (Researcher) Nieves García Gisbert (PhD Student) Lierni Fernández Ibarrondo (Technician) Francesc Garcia Pallarols (Technician) Joan Gibert Fernández (Technician) María Elena Torres Grande (Technician)

The group is mainly interested in the study of myeloproliferative neoplasms and lymphomas. We are now studying molecular markers in chronic myeloproliferative neoplasms, mainly driver mutations but also mutations in epigenetic modifiers and genes involved in the splicing mechanism, and their role in monitoring the response to cytoreductive therapy and in patient outcome. In addition, the group is searching for new mutations using exome sequencing techniques in patients with essential thrombocythemia unmutated for JAK2, CALR and MPL genes. Moreover, the role of circulating DNA as a tool to diagnose and monitor the response to therapy in myeloid neoplasms is an ongoing research project.

44 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Applied Clinical Research in Hematological Malignances

Another area of research is the use of NGS and circulating DNA to study the diagnostic and prognostic role of mutations in B-cell neoplasms (diffuse large B-cell lymphomas and follicular lymphoma). We are focused in analyzing the relationship of these molecular biomarkers with response to therapy and outcome. Another area of clinical research in lymphoma focuses on the usefulness of natriuretic peptides and cardiovascular risk scales for predicting anthracycline-induced cardiomyotoxicity in patients with lymphomas.

Main Publications

• Bellosillo B, Montagut C. High-accuracy liquid biopsies. Nat Med 2019; 25(12): 1820- 1821. IF 30.641. Q1. • Vidal J, Bellosillo B, Santos Vivas C, García-Alfonso P, Carrato A, Cano MT, García- Carbonero R, Élez E, Losa F, Massutí B, Valladares-Ayerbes M, Viéitez JM, Manzano JL, Gallego J, Pairet S, Capellá G, Salazar R, Tabernero J, Aranda E, Montagut C. Ultra- selection of metastatic colorectal cancer patients using Next Generation Sequencing to improve clinical efficacy of anti-EGFR therapy. Ann Oncol 2019; 30(3): 439-446. IF 14.196. D1. • Ferraro MP, Gimeno-Vázquez E, Subirana I, Gómez M, Díaz J, Sánchez-González B, García-Pallarols F, Martínez L, Ble M, Molina L, Belarte LC, Abella E, Elosua R, Comín- Colet J, Salar A. Anthracycline-induced cardiotoxicity in diffuse large B-cell lymphoma: NT-proBNP and cardiovascular score for risk stratification. Eur J Haematol 2019; 102(6): 509-515. IF 2.217. Q3. See all Publications

Ongoing Research Projects

• Mutation characterization and tumor mutational burden in early progressor follicular lymphoma. - Financing institution: Gilead grant (GLD18/00117) - Period: from 2019 to 2021 - Principal investigator: Salar Silvestre, Antonio See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 45 Cancer Applied Clinical Research in Hematological Malignances

Clinical Trials Signed in 2019

• A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared with Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma - Protocol: BGB-3111-305 - Sponsor: BeiGene, Ltd. - Budget: 41,587.5 € - Principal investigator: Gimeno Vázquez, Eva • Estudio de fase 2, abierto y de un solo grupo, del inhibidor de HDAC oral abexinostat en pacientes con linfoma folicular en recaída o refractario - Protocol: XYN-601 - Sponsor: Xynomic Pharmaceuticals - Budget: 13,099.2 € - Principal investigator: Salar Silvestre, Antonio • Estudio multicéntrico, abierto y de un solo grupo de “Gazyva” en infusión de corta duración (ICD) en pacientes con linfoma folicular avanzado no tratado previamente - Protocol: MO40597 - Sponsor: Roche Farma S.A. - Budget: 19,496 € - Principal investigator: Salar Silvestre, Antonio • Estudio en fase I, multicéntrico y abierto para evaluar la seguridad, tolerabilidad y farmacocinética de dosis crecientes de RO7082859, administradas después de una dosis única fija de obinutuzumab (Gazyva®/Gazyvaro™), a pacientes con linfoma no Hodgkin de linfocitos B recidivante/resistente - Protocol: NP30179 - Sponsor: Roche Farma S.A. - Budget: 94,230 € - Principal investigator: Salar Silvestre, Antonio • Treatment with Daratumumab in relapsed / refractory Multiple Myeloma patients in clinical care practice in Catalonia. A retrospective study - Protocol: GEM-DAR-2018-01 - Sponsor: Grup per a l’Estudi del Mieloma Múltiple i l’Amiloïdosi de Catalunya (GEMMAC) - Budget: No economic compensation - Principal investigator: Abella Monreal, Eugenia

46 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Applied Clinical Research in Hematological Malignances

• Un estudio retrospectivo de observación de cohortes sobre la monoterapia con lenalidomida en el linfoma difuso de células B grandes refractario o recidivante (LDCBG RR) para generar un control histórico para el Ensayo clínico MOR208C203 - Protocol: MOR208C206 - Sponsor: MorphoSys AG - Budget: 1,500 € - Principal investigator: Salar Silvestre, Antonio • A Phase II Open-label Multicenter Study to Assess the Efficacy and Safety of AFM13 in Patients with Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT) - Protocol: AFM13-202 - Sponsor: Affimed GMBH - Budget: 109,821.95€ - Principal investigator: Sánchez González, Blanca

Awards

• Eugenia Abella Monreal. Impacto de la incorporación de un Gestor de Casos en el diagnóstico y seguimiento de pacientes con Mieloma Múltiple Sintomático. 3rd edition of the Innovation in the Area of Health Award. Universidad de Alcalá de Henares. March 2019.

Appointments

• Antonio Salar Silvestre. GELTAMO Group Treasurer.

Outreach

Conferences, Seminars and Courses

• Antonio Salar. Moderator and speaker. Simposium Congreso SEHH. València, 25 October 2019. • Antonio Salar. Speaker. 1st Azerbaijan International Congress of Hematology Specialist. Azerbaijan, 22-25 May 2019. • Beatriz Bellosillo. Teacher. Curso online de Biopsia líquida. March 2019. • Beatriz Bellosillo. Speaker. MPN&MPNr-EuroNet XIVth Workshop. Belgrado, Serbia, 8-10 May 2019. • Blanca Sánchez-González. Guía GELTAMO de linfoma de Hodgkin 2019. ISBN: 978- 84-09-11251-7.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 47 Cancer Applied Clinical Research in Hematological Malignances

Dissemination to Society and Initiatives of Citizen Participation

• Blanca Sánchez-González. Coordinator. Jornada para pacientes con PTI. Barcelona, 7 May 2019. • Beatriz Bellosillo. Què representa per a l’investigador posar en marxa el seu projecte de recerca gràcies a la suma d’esforços dels donants a La Marató, la primera iniciativa solidària del país? Masterclass of the La Marató de TV3. Campus Hospital del Mar, 9 April 2019.

48 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Colorectal Neoplasms Clinical and Translational Research

> Cancer RESEARCH GROUP

Group Leader Members Xavier Bessa Caserras Sandra Alonso Gonçálvez (Researcher) [email protected] Marco Antonio Álvarez González (Researcher) Josep Maria Dedeu Cuscó (Researcher) Luís Grande Posa (Researcher) Lucas Ilzarbe Sánchez (Researcher) Lucía Márquez Mosquera (Researcher) Xavier Mayol Girbau (Researcher) Marta Pascual Damieta (Researcher) Miguel Pera Román (Researcher) Silvia Salvans Ruiz (Researcher) Agustín Seoane Urgorri (Researcher) Cristina Álvarez Urturi (PhD Student) Fausto Riu Pons (PhD Student) M. Francisca Murciano Gonzalo (Technician)

The main strategic objective is to further our understanding of the pathogenesis of various neoplastic colorectal processes, from polyps to colorectal cancer, as well as their prevention and treatment. Our research focuses on identifying the factors relating to the development of metachronous neoplastic lesions, particularly advanced colorectal adenomas, to improve patient monitoring, and study how the inflammatory response to surgery influences the oncological outcome, identifying disease progression biomarkers in patients with colorectal cancer. Ongoing projects are:

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 49 Cancer Colorectal Neoplasms Clinical and Translational Research

1) Optimization of the surveillance of colon polyps. Development of an index for the risk of recurrence based on environmental, clinical, morphological, histological and molecular factors. 2) Prevention of colorectal cancer in the intermediate-risk population by means of genomic and microbiomic biomarkers (CRIPREV) PERIS (SLT002/16/00398). 3) Evaluation of ctDNA and deep learning in the detection of minimal residual disease in invasive polyps (pTN1). 4) Validation of postoperative serum levels of VEGF as a predictive biomarker of recurrence after surgery in patients with CRC who have undergone surgery with curative intent (FAECP grant). 5) Metabolic phenotyping of patients with CRC who have undergone surgery with curative intent to develop a profile of metabolites as predictive biomarkers of recurrence (ISCIII grant). 6) Liquid biopsy to assess minimal residual disease after surgery for colorectal cancer: an insight into the association between anastomotic leak and tumor recurrence (ISCIII grant).

Main Publications

• Albéniz E, Álvarez-González MA, Espinós JC, Nogales O, Guarner C, Alonso P, Rodríguez-Téllez M, Herreros-de-Tejada A, Santiago J, Bustamante-Balén M, Sánchez JR, Ramos-Zabala F, Valdivielso E, Martínez-Alcalá F, Fraile M, Elosua A, Guerra-Veloz MF, Beroiz BI, Capdevila F, Enguita-Germán M. Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding. Gastroenterology 2019; 157(5): 1213-1221.e4. IF 19.233. D1. • Puig I, López-Cerón M, Arnau A, Rosiñol Ò, Cuatrecasas M, Herreros-de-Tejada A, Ferrández Á, Serra-Burriel M, Nogales O, Vida F, de Castro L, López-Vicente J, Vega P, Álvarez-González MA, González-Santiago J, Hernández-Conde M, Díez-Redondo P, Sánchez LR, Gimeno-García AZ, Burgos A, García-Alonso FJ, Bustamante-Balén M, Martínez-Bauer E, Peñas B, Pellise M, EndoCAR group, Spanish Gastroenterological Association and the Spanish Digestive Endoscopy Society. Collaborators. Accuracy of the Narrow-band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps. Gastroenterology 2019; 156(1): 75-87. IF 19.233. D1. • Vleugels JLA, Hassan C, Senore C, Cassoni P, Baron JA, Rex DK, Ponugoti PL, Pellise M, Parejo S, Bessa X, Arnau-Collell C, Kaminski MF, Bugajski M, Wieszczy P, Kuipers EJ, Melson J, Ma KH, Holman R, Dekker E, Pohl H. Diminutive Polyps With Advanced Histologic Features Do Not Increase Risk for Metachronous Advanced Colon Neoplasia. Gastroenterology 2019; 156(3): 623-634. IF 19.233. D1.

50 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Colorectal Neoplasms Clinical and Translational Research

• Bleijenberg AGC, IJspeert JEG, Carballal S, Pellise M, Jung G, van Herwaarden YJ, Bisseling TM, Nagtegaal ID, van Leerdam ME, Spaander MCW, van Lelyveld N, Bessa X, Rodríguez-Alcalde D, Bastiaansen BAJ, de Klaver W, Bemelman WA, Bujanda L, Koornstra JJ, Rivero L, Rodríguez-Moranta F, Balaguer F, Dekker E. Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study. Am J Gastroenterol 2019; 114(9): 1512-1519. IF 10.241. D1. • Bisschops R, Manning J, Clayton LB, Ng Kwet Shing R, Álvarez-González MA, MORA Study Group. Colon cleansing efficacy and safety with 1 L NER1006 versus 2 L polyethylene glycol + ascorbate: a randomized phase 3 trial. Endoscopy 2019; 51(1): 60-72. IF 6.381. D1. See all Publications

Ongoing Research Projects

• Biomarcadores pronósticos de recurrencia tras cirugía del cáncer colorrectal: Estudio de los cambios metabólicos y del contenido proteico y de miRNA de las vesículas extracelulares - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00458) - Period: from 2016 to 2020 - Principal investigator: Pera Román, Miguel • Early biomarkers in circulating a 4B7 + T cells to predict response to Vedolizumab in inflammatory bowel disease patients - Financing institution: Takeda Pharmaceutical Company Limited (IISR-2016- 101479) - Period: from 2016 to 2019 - Principal investigator: Márquez Mosquera, Lucía • Diverticulitis agua y peoplasia avanzada de colon. Cuando realizar la endoscopia. Estudio ADACOLON (Acute Diverticulitis Advanced COLOnic Neoplasia) - Financing institution: Asociación Española de Gastroenterología - Period: from 2019 to 2021 - Principal investigator: Seoane Urgorri, Agustín • Monitorización intraoperatoria de los nervios autonómicos en la cirugía del cáncer de recto: estudio prospectivo para valorar los resultados funcionales urogenitales y anorectales - Financing institution: Fundación Asociación Española de Coloproctología - Period: from 2019 to 2021 - Principal investigator: Alonso Gonçálvez, Sandra See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 51 Cancer Colorectal Neoplasms Clinical and Translational Research

Clinical Trials Signed in 2019

• Retrospective observational study to describe treatment patterns and health care resource utilization associated with complex perianal fistula in Crohn’s disease - Protocol: IBD-5003 - Sponsor: Takeda Pharmaceutical Company Limited - Budget: 7,500 € - Principal investigator: Márquez Mosquera, Lucía • Safety of IBD drugs during pregnancy and breastfeeding: mothers and babies outcomes (Dumbo registry) - Protocol: GET-VED-2018-01 - Sponsor: Grupo Español de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) - Budget: No economic compensation - Principal investigator: Márquez Mosquera, Lucía • Efecto de fluidoterapia agresiva frente a fluidoterapia no agresiva en la fase precoz de la pancreatitis aguda: ensayo clínico aleatorizado multicéntrico, estudio Waterfall - Protocol: Waterfall-2019 - Sponsor: Hospital General Universitario de Alicante - Budget: No economic compensation - Principal investigator: Ilzarbe Sánchez, Lucas

Appointments

• Miguel Pera. Member of the International Committee. American Society of Colon and Rectal Surgeons. September 2019.

Outreach

Conferences, Seminars and Courses

• Xavier Bessa. Moderator. Controvèrsies en digestologia. XXIX Congrés de la Societat Catalana de Gastroenterologia. Parc de Salut Mar. Lleida, 30 January 2020. • Actualización en la prevención del cáncer colorrectal (CCR). Controversias en el seguimiento de los pacientes con pólipos y antecedentes familiares de CCR (09/026597-MD). 102º Curso de Patología Digestiva “Avances en Patología Digestiva”. Hospital de Sant Pau. Barcelona, 21 November 2019.

52 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Gastroesophageal Carcinogenesis

> Cancer RESEARCH GROUP

Group Leader Members Manuel Ramón Pera Román Gabriel Gil Gómez (Researher) [email protected] Mar Iglesias Coma (Researcher) Marta Garrido Saldaña (Technician)

The sequential process prior to the appearance of a gastric or esophageal adenocarcinoma is a sequential histologically well-defined process characterized by the appearance of an intestinal phenotype. In the first stages of gastro-esophageal carcinogenesis the expression of intestinal markers, as intestinal transcription factors (CDX2), mucin genes (MUC2 and MUC4), intestinal enzymes and others, can be detected. We study the molecular mechanisms that can be initiating these processes, through the regulation of transcription factors inducing the acquisition of the intestinal phenotype. In the esophagus, the development of columnar metaplasia (Barrett’s esophagus) is a response to a chronic gastroesophageal reflux injury and is a major risk factor for esophageal adenocarcinoma. Patients undergoing esophagectomy with a gastric conduit reconstruction develop columnar metaplasia in the remnant esophagus on a background of significant reflux, providing a useful model to study the early molecular events in the development of Barrett’s esophagus. MiRNAs expression profiles may identify a characteristic signature that could distinguish between normal squamous epithelium, esophagitis, cardiac-type epithelium, and intestinal metaplasia.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 53 Cancer Gastroesophageal Carcinogenesis

We have identified miR24-3p as a negative regulator of CDX2, a transcription factor involved in the development of Barrett’s esophagus, in samples of cardiac-type mucosa with different stages of intestinalization. We are currently analysing the value of a metabolic signature identified by a metabolomics approach as a biomarker for the early detection, treatment optimization, and follow-up of patients with gastroesophageal cancer.

Main Publications

• Jericó C, Osorio J, García-Erce JA, Pera MR. Patient Blood Management strategies for iron deficiency anemia management in gastric cancer. Eur J Gastroenterol Hepatol 2019; 31(4): 547-548. IF 2.198. Q3. • Osorio J, Rodríguez-Santiago J, Roig J, Pera MR. Proyectos de estandarización del tratamiento del cáncer de la unión esofagogástrica: centralización, registros y formación. Cir Esp 2019; 97(8): 470-476. IF 0.835. Q4. See all Publications

Ongoing Research Projects

• Impacto de la fragilidad sobre los resultados postoperatorios de la cirugía del cáncer gástrico [TOREGA] - Financing institution: Asociación Española de Cirujanos - Period: from 2018 to 2020 - Principal investigator: Pera Román, Manuel Ramón See all Projects

Clinical Trials Signed in 2019

• Validación de la calidad de los datos del Registro EURECCA de Cáncer Esofagogástrico en España y resultados iniciales - Protocol: EURECCA - Sponsor: Fundació Institut Mar d’Investigacions Mèdiques - Budget: No economic compensation - Principal investigator: Pera Román, Manuel Ramón • Distribution of lymph node metastases in esophageal carcinoma. TIGER study - Sponsor: Amsterdam UMC (AMC) - Budget: No economic compensation - Principal investigator: Pera Román, Manuel Ramón

54 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Gastroesophageal Carcinogenesis

Outreach

Conferences, Seminars and Courses

• Invited to deliver the prestigious conference “Diego Figuera Aymerich” at the 25 Congreso de la Sociedad Española de Investigaciones Quirúrgicas (SEIQ). Hospital Clínic, Barcelona, 12-13 December 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Hoja de Ruta: Cáncer Gástrico. Fundación Más Que Ideas. Madrid, 21 June 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 55 Cancer Gastroesophageal Carcinogenesis

Genitourinary Cancer

> Cancer RESEARCH GROUP

Group Leader Members Josep Lloreta Trull Lluís Cecchini Rosell (Researcher) [email protected] Albert Francés Comalat (Researcher) Lluís Fumadó Ciutat (Researcher) Silvia Hernández Llodrà (Researcher) Núria Juanpere Rodero (Researcher) Glòria Nohales Taurines (Researcher) Alejo Rodríguez-Vida Rodríguez (Researcher) Marta Lorenzo Pérez (Technician) Susana Pinó Donnay (Technician) Laura Segalés Tañà (Technician)

Prostate cancer is the most common non-cutaneous cancer in men, and urinary bladder cancer is the fourth most common overall in both sexes. In addition to their prevalence, there are specific features of their respective natural histories that make them two of the cancers that generate some of the highest economic costs and they are associated with high morbidity rates, thus both have a significant impact on patients’ quality of life and on health care costs. These are two different models of carcinogenesis, reflecting diverse aspects of cancer biology. Two major pathways with different molecular, pathological and clinical profiles are well known in bladder cancer. A further advance relies on the identification of several specific molecular subclasses similar to those identified in breast cancer. Also in prostate cancer, the relatively unpredictable behavior of the disease appears to be

56 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Genitourinary Cancer

related to different molecular subfamilies, namely, the complex subset of translocation- associated tumors, and the still poorly defined miscellaneous group of tumors not related to gene rearrangements. Furthermore, in both tumors, it has been suggested that inflammatory and immunological responses may be involved in their initiation and progression and these are regarded as new avenues for therapeutic intervention. In both tumors, there is a high demand for markers of early diagnosis, follow-up, and response to therapy, as well as for new therapeutic targets and for parameters that allow a more personalized management of patients. Our objectives are to identify genetic signatures that may be involved in the transition from a hypothetical latent phase to a clinically significant phase, as well as markers of progression and advanced disease, in order to better understand the natural history of bladder and prostatic carcinoma and to design adequate treatment strategies for early detection, monitoring, treatment stratification, and follow-up, tailored for the personalized management of each patient.

Main Publications

• Powles T, Kockx M, Rodríguez-Vida A, Duran I, Crabb SJ, van der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med 2019; 25(11): 1706-1714. IF 30.641. D1. • Castro E, Romero-Laorden N, del Pozo A, Lozano R, Medina A, Puente J, Piulats JM, Lorente D, Saez MI, Morales-Barrera R, et al. (Rodríguez-Vida A) PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 2019; 37(6): 490-503. IF 28.245. D1. • Bellmunt J, Rodríguez-Vida A. Treatment of Metastatic Urothelial Cancer in 2018. JAMA Oncol 2019; 5(6): 904-905. IF 22.416. D1. • Marin J, Dot I, Boguña M, Cecchini L, Zapatero A, Gracia-Arnillas MP, Pascual S, Vilà C, Castellví A, Pérez-Terán P, Gea J, Masclans JR. Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation. Int Care Med 2019; 45(4): 488-500. IF 18.967. D1. • Grimm MO, Bex A, De Santis M, Ljungberg B, Catto JWF, Rouprêt M, Hussain SA, Bellmunt J, Powles T, Wirth M, van Poppel H. Safe Use of Immune Checkpoint Inhibitors in the Multidisciplinary Management of Urological Cancer: The European Association of Urology Position in 2019. Eur Urol 2019; 76(3): 368-380. IF 17.298. D1. See all Publications

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 57 Cancer Genitourinary Cancer

Ongoing Research Projects

• Validación clínica y mecanismos de acción de las alteraciones moleculares con valor predictivo de progresión en el cáncer de próstata: algoritmo molecular de la carcinogénesis prostática - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00452) - Period: from 2016 to 2019 - Principal investigator: Lloreta Trull, Josep See all Projects

Clinical Trials Signed in 2019

• PROSTRATEGY: ensayo clínico aleatorizado, fase II/III, con múltiples brazos y multietapa, de estrategias de inmunoterapia en cáncer de próstata metastásico sensible a hormonas. Fase piloto - Protocol: SOGUG-2016-A-IEC (PRO)-14 - Sponsor: Grupo Español de Oncología Genitourinaria (SOGUG) - Budget: 12,000 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Ensayo fase III, aleatorizado, abierto, controlado, multicéntrico, internacional de durvalumab en combinación con el tratamiento estándar con quimioterapia y durvalumab en combinación con tremelimumab y el tratamiento estándar con quimioterapia frente al tratamiento estándar con quimioterapia solo, en primera línea en pacientes con cáncer urotelial localmente avanzado irresecable o metastásico “NILE” - Protocol: D933SC00001 - Sponsor: AstraZeneca AB - Budget: 89,692.8 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Registro de respuestas completas a sunitinib en pacientes españoles con carcinoma renal metastásico - Protocol: A6181227 (PFI-SUN-2018-01) - Sponsor: Pfizer - Budget: 1,600 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo

58 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Genitourinary Cancer

• Ensayo de fase 3, aleatorizado y doble ciego de pembrolizumab (MK-3475) más enzalutamida frente a un placebo más enzalutamide en participantes con cáncer de próstata resistente a la castración metástasico (CPRCm) (KEYNOTE-641) - Protocol: MK-3475-641 - Sponsor: Merck Sharp & Dohme de España S.A. - Budget: 185,748 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio de fase 3, aleatorizado y abierto de pembrolizumab (MK-3475) más olaparib frente a acetato de abiraterona o enzalutamida en participantes con cáncer de próstata resistente a la castración metastásico (CPRCm) que no son seleccionados por defectos en el sistema de reparación por recombinación homóloga y que han mostrado fracaso con el tratamiento previo con un fármaco hormonal de última generación (FHUG) y quimioterapia (KEYLYNK-010) - Protocol: MK-7339-010 - Sponsor: Merck Sharp & Dohme de España S.A. - Budget: 134,804 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio fase 3, aleatorizado, controlado frente a placebo, doble ciego de Niraparib en combinación con Acetato de Abiraterona y Prednisona versus Acetato de Abiraterona y prednisona para el tratamiento de sujetos con cáncer de próstata metastásico - Protocol: 64091742PCR3001 - Sponsor: Janssen-Cilag - Budget: 41,200 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio de fase 3, aleatorizado y doble ciego para evaluar pembrolizumab (MK-3475) perioperatorio + quimioterapia neoadyuvante frente a un placebo perioperatorio + quimioterapia neoadyuvante en participantes con cáncer de vejiga con invasión muscular que son aptos para recibir cisplatino (KEYNOTE-866) - Protocol: MK-3475-866 - Sponsor: Merck Sharp & Dohme de España S.A. - Budget: 113,185 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio de fase 3 aleatorizado de cistectomía más pembrolizumab perioperatorio frente a cistectomía sola en participantes con cáncer de vejiga con invasión muscular que no son aptos para recibir cisplatino (KEYNOTE-905) - Protocol: MK-3475-905 - Sponsor: Merck Sharp & Dohme de España S.A. - Budget: No economic compensation - Principal investigator: Rodríguez-Vida Rodríguez, Alejo

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 59 Cancer Genitourinary Cancer

• Estudio de fase 3, aleatorizado y doble ciego de pembrolizumab (MK-3475) más docetaxel más prednisona frente a un placebo más docetaxel más prednisona en participantes con cáncer de próstata resistente la castración metastásico (CPRCm) sin tratamiento previo con quimioterapia que han mostrado progresión con un fármaco hormonal de última generación (FHUG) (KEYNOTE-921) - Protocol: MK-3475-921 - Sponsor: Merck Sharp & Dohme de España S.A. - Budget: 173,324 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio fase 3b, aleatorizado, doble ciego, de nivolumab en combinación con ipilimumab frente a nivolumab en monoterapia en pacientes con carcinoma de células renales avanzado, no tratado previamente y con factores de riesgo intermedio o alto - Protocol: CA2098Y8 - Sponsor: Bristol-Myers Squibb International Corporation (BMSIC) - Budget: 52,159.8€ - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Ensayo fase 2 de nivolumab más ipilimumab, ipilimumab en monoterapia o cabazitaxel en varones con cáncer de próstata metastásico resistente a la castración - Protocol: CA209-650 - Sponsor: Bristol-Myers Squibb International Corporation (BMSIC) - Budget: 70,062 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • IRONMAN-ES: Estudio prospectivo observacional de parámetros clínicos y biomarcadores en cáncer de próstata avanzado en hospitales de España - Protocol: IRONMAN-ES - Sponsor: Fundacio Privada Institut d’Investigació Oncològica Vall d’Hebron (VHIO) - Budget: 8,400 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio de Fase 1b-2 para evaluar la seguridad, eficacia, farmacocinética y farmacodinamia de erdafitinib más JNJ-63723283, un anticuerpo monoclonal anti-PD-1, en sujetos con cáncer urotelial metastásico o no resecable con determinadas alteraciones del gen del FGFR - Protocol: 2756493BLC2002 - Sponsor: Janssen-Cilag - Budget: 18,200 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo

60 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Genitourinary Cancer

• Estudio de fase 2, aleatorizado, no comparativo y abierto de NKTR-214 en combinación con nivolumab y quimioterapia en pacientes con cáncer urotelial localmente avanzado o metastásico no aptos para recibir cisplatino y con expresión baja de PD L1 - Protocol: NEKTAR 18-214 - Sponsor: Nektar Therapeutics - Budget: 37,680 € - Principal investigator: Rodríguez-Vida Rodríguez, Alejo • Estudio observacional sobre el manejo en la práctica clínica del cáncer de próstata resistente a la castración con estatus metastásico desconocido: Estudio Afrodita - Protocol: 212082PCR4058 - Sponsor: Janssen-Cilag - Budget: 1,950 € - Principal investigator: Fumadó Ciutat, Lluís

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 61 Localised Hyperthermia Therapies

> Cancer RESEARCH GROUP

Group Leader Members Fernando Burdío Pinilla Clara Pañella Velázquez (Researcher) [email protected] Patricia Sánchez Velázquez (Researcher) María Lina Villamonte Román (Technician)

The primary objective of the group is scientific production and technological innovation in the field of the application of high-frequency current to generate heat in biological tissues, aimed at local cell destruction that is minimally invasive for tissue pathologies, especially (but not exclusively) of human neoplasms.

Main Publications

• Van Hilst J, de Rooij T, Klompmaker S, Rawashdeh M, Aleotti F, Al-Sarireh B, Alseidi A, Ateeb Z, Balzano G, Berrevoet F, et al. (Poves I), European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study. Ann Surg 2019; 269(1): 10-17. IF 9.476. D1. • Gómez-Rubio P, Piñero J, Molina-Montes E, Gutiérrez-Sacristán A, Márquez M, Rava M, Michalski CW, Farré A, Molero X, Löhr M, et al. (Iglesias M, Iizalbe L, Poves I), PanGenEU Study Investigators. Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches. Int J Cancer 2019; 144(7): 1540-1549. IF 4.982. Q1.

62 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Localised Hyperthermia Therapies

• Andaluz A, Ewertowska E, Moll X, Aguilar A, García F, Fondevila D, Quesada R, Berjano E, Grande L, Burdío F. Endoluminal radiofrequency ablation of the main pancreatic duct is a secure and effective method to produce pancreatic atrophy and to achieve stump closure. Sci Rep 2019; 9(1): 5928. IF 4.011. Q1. • López-Alonso B, Hernáez Á, Sarnago H, Naval A, Güemes A, Junquera C, Burdío JM, Castiella T, Monleón E, Gracia-Llanes J, Burdío F, Mejía E, Lucía O. Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator. Sci Rep 2019; 9(1): 2647. IF 4.011. Q1. • Quesada R, Simón C, Radosevic A, Poves I, Grande L, Burdío F. Morphological changes of the pancreas after pancreaticoduodenectomy. Sci Rep 2019; 9: 14517. IF: 4.011. Q1. See all Publications

Ongoing Research Projects

• Electroporación selectiva en hígado tumoral por medio de infusión de suero hipersalino vía portal - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00468) - Period: from 2018 to 2020 - Principal investigator: Burdío Pinilla, Fernando See all Projects

Awards

• Fernando Burdío Pinilla. National Surgery Award 2019. Asociación Española de Cirujanos. November 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 63 Mechanisms of Tumorigenesis and Tumor Progression

> Cancer RESEARCH GROUP

Group Leader Members Antonio García de Herreros Luis Eugenio Barranco Priego (Researcher) Madueño Josep Baulida Estadella (Researcher) [email protected] Beatriz del Valle Pérez (Researcher) Gemma Mancebo Moreno (Researcher) Neus Martínez Bosch (Researcher) Marina Bruch Oms (PhD Student) David Cabrerizo Granados (PhD Student) Héctor Franco Valls (PhD Student) Aida Mestre Farrera (PhD Student) Raúl Martínez Izquierdo (Technician) Mireia Moreno Merino (Technician) Raúl Peña Arranz (Technician) Silvia Geeraerd (Research Assistant)

The group’s interest is the study of the mechanisms controlling the acquisition of invasiveness by epithelial tumours as the first step in tumour metastasis. We are currently investigating several aspects of this process, such as epithelial-to- mesenchymal transition (EMT), a conversion that provides tumour cells with more invasion and also resistance to chemotherapeutic drugs. We are especially analysing the role of Snail1 transcriptional factor, required for EMT and also necessary for the activation of cancer-associated fibroblasts (CAFs).

64 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Epithelial-Mesenchymal Transition in Tumour Development

We are currently studying how Snail1 expression is regulated both transcriptionally and post-translationally, since Snail1 protein half-life is finely tuned. Moreover, using CAFs deprived of Snail1, we are assessing the effect of CAF activation in the growth, invasion, and immune response of epithelial tumours. We are also interested in the Snail1-dependent molecular pathways in fibroblasts involved in the activation of tumour cell invasion. Finally, we are also investigating the role of Snail1 in other tumour microenvironment cells, such as endothelial cells. A second line of research is led by Dr. Pilar Navarro within a framework partnership agreement with the Institute of Biomedical Research of Barcelona (Associated Unit IMIM-IIBB CSIC, created in June 2018) and is focused on exploring other molecular mechanisms underlying tumor progression; specifically, the relevance of galectin- mediated tumour-stroma crosstalk. Moreover, considering that cancer is a genetic disease caused by changes in gene expression during malignant transformation, we are also very interested in deciphering how these genetic changes are regulated by RNA translational control. The research group was recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a research group (2017 SGR 24; Principal investigator: Antonio García de Herreros Madueño).

Main Publications

• Martínez-Bosch N, Rodríguez-Vida A, Juanpere N, Lloreta J, Rovira A, Albanell J, Bellmunt J, Navarro P. Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities. Nat Rev Urol. 2019; 16(7): 433-445. IF 9.333. D1. • Lambies G, Miceli M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderon I, Atanassov BS, Dent SYR, Arribas J, García de Herreros A, Díaz VM. TGFβ- activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res 2019; 79(1): 33-46. IF 8.378. Q1. • Baulida J, Díaz VM, García de Herreros A. Snail1: a transcriptional factor controlled at multiple levels. J, Clin. Med 219; 8(6): E757. IF 5.688. D1. • Sala-Romanyà L, Franco-Valls H, Stanisavljevic J, Curto J, Vergés J, Peña R, Duch P, Alcaraz J, García de Herreros A, Baulida J. Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. Int J Cancer 2019; 145(11): 3064-3077. IF 4.982. Q1. • García de Herreros A, Duñach M. Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization. Cells 2019, 8(10): E1148. IF 4.829. Q1. See all Publications

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 65 Cancer Epithelial-Mesenchymal Transition in Tumour Development

Ongoing Research Projects

• Entendiendo el papel de Snail1 en la metástasis: análisis de la acción de los fibroblastos activos - Financing institution: Ministerio de Economía y Competitividad (SAF2016- 76461-R) - Period: From 2016 to 2019 - Principal investigator: García de Herreros Madueño, Antonio See all Projects

Clinical Trials Signed in 2019

• Ensayo Clínico PALOMA II: Ensayo clínico, aleatorizado, abierto, muticéntrico, de grupos paralelos y con grupo control, para la evaluación del efecto de PAPILOCARE® en la normalización de las alteraciones citológicas del cuello del útero causadas por el Virus Papiloma Humano - Protocol: PALOMA II - Sponsor: Procare Health Iberia, S.L. - Budget: 9,450 € - Principal investigator: Mancebo Moreno, Gemma; Solé Sedeño, Josep Maria

Theses

• Lambies G. Deubiquitinating enzymes stabilizing Snail1 transcription factor: a role for USP27X in epithlia. Universitat Pompeu Fabra - Directors: Díaz VM, García de Herreros Madueño, Antonio - Date of defense: 10/01/2019 • Olivera R. New roles for Snail1 expressing Cancer-Associated Fibroblasts (CAFs) during primary tumor progression and secondary niche colonization. Universitat Pompeu Fabra - Director: García de Herreros Madueño, Antonio - Date of defense: 19/07/2019

66 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Molecular Cancer Therapeutics

> Cancer RESEARCH GROUP

Group Leader Joan Albanell Mestres

[email protected]

Members Andrea Edo Guimerà (Technician) Miguel Alejandro Galindo Campos (Technician) Edurne Arriola Aperribay (Researcher) Susana Galtés Cruces (Technician) Montserrat Arumí Uria (Researcher) Meritxell García Ventura (Technician) Joaquim Bellmunt Molins (Researcher) Soledad González Gallardo (Technician) Alexandre Calon (Researcher) Cristina Guardia Valenzuela (Technician) David Casadevall Aguilar (Researcher) Patricia Guillem Gómez (Technician) Antoni Celià Terrassa (Researcher) Jenniffer Lissethe Linares Aceituno (Technician) Marta Guix Arnau (Researcher) David López Segura (Technician) Max Hardy Werbin (Researcher) Marta Macià Valldeperas (Technician) Belén Lloveras Rubio (Researcher) Daniel Martínez García (Technician) María Martínez García (Researcher) Gemma Martínez Peña (Technician) Clara Montagut Viladot (Researcher) Tamara Martos Cárdenas (Technician) Elisa Isabel Rivas (Researcher) Silvia Menéndez Romero (Technician) Ana Rovira Guerin (Researcher) Sergio Muñoz Villaverde (Technician) Mohammad Ali Sabbaghi Mehrjardi (Researcher) Francesc Olivares Vegas (Technician) Irene Sangrador Escrig (Researcher) Iván Pérez Núñez (Technician) Sònia Servitja Tormo (Researcher) Xènia Riera Garcia (Technician) Ignacio Tusquets Trias de Bes (Researcher) Noemí Rodríguez Fernández (Technician) Judith Alonso Lezcano (Technician) Catalina Rozalén Miralles (Technician) Judit Amenós Sabaté (Technician) Marouane Sahraoui (Technician) Oriol Arpí Llucià (Technician) Lluïsa Tarès Montserrat (Technician) Randa Ben Azaiz Ben Lahsen (Technician) Xavier Villanueva Castelltort (Technician) Laia Cano Serrano (Technician) Michelle von Locquenghien (Technician) Laura Cardona Grifoll (Technician) Arnau Zafra Ponce (Technician) Clara Carreras Vila (Technician) Asel·la Fernàndez Gómez (Research Assistant) Mariona Dalmau Längst (Technician) Lorena Tomás Marín (Research Assistant)

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 67 Cancer Molecular Cancer Therapeutics

Our goal is to improve human cancer treatment through preclinical research with novel anticancer agents/combinations, and translational studies in clinical settings. The group includes three medical oncologists who lead competitive projects in breast (Joan Albanell), colon (Clara Montagut), and lung cancer (Edurne Arriola). We are organized into two areas: Preclinical laboratory (led by Ana Rovira) and Clinical research (led by Ignasi Tusquets). With regard to clinical research, we are working on bone health in women with breast cancer (Sònia Servitja), Phase I trials (María Martínez) and oncogeriatrics (Laura Visa, María Pi-Figueras). Our integration into one single group has proven to be a successful strategy since it allows for the sharing of resources, expertise, knowledge and results, which improves the performance of individual PIs far beyond the collaboration between traditional independent groups. The group recently incorporated two Miguel Servet investigators (Alexandre Calon and Toni Celià-Terrassa). A. Calon works on the role of stroma in cancer, and T. Celià-Terrassa on stem cells in breast cancer. Both of them were attached to the group but will evolve soon to independently recognized IMIM groups within the cancer programme. The group is funded by CIBERONC and AGAUR.

Main Publications

• Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol 2019; 37(17): 1460-1469. IF 28.245. D1. • Colomer C, Margalef P, Villanueva A, Vert A, Pecharromán I, Solé L, González-Farré M, Alonso J, Montagut C, Martínez M, Bertran J, Borrás E, Iglesias M, Sabido E, Bigas A, Boulton S, Espinosa L. IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer. Mol Cell 2019; 75(4): 669-682. IF 14.548. D1. • Horwich A, Babjuk M, Bellmunt J, Bruins HM, Reijke TM, Santis M, Gillessen S, James N, Maclennan S, Palou J, et al. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi- stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees. Ann Oncol 2019; 30(11): 1697-1727. IF 14.196. D1. • Vidal J, Bellosillo B, Santos C, García-Alfonso P, Carrato A, Cano MT, García- Carbonero R, Élez E, Losa F, Massutí B, Valladares-Ayerbes M, Viéitez JM, Manzano JL, Gallego J, Pairet S, Capellá G, Salazar R, Tabernero J, Aranda E, Montagut C. Ultra- selection of metastatic colorectal cancer patients using Next Generation Sequencing to improve clinical efficacy of anti-EGFR therapy. Ann Oncol 2019; 30(3): 439-446. IF 14.196. D1.

68 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Molecular Cancer Therapeutics

Ongoing Research Projects

• Uncovering resistance to monoclonal antibodies in colorectal and breast cancer - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PIE15/00008) - Period: from 2016 to 2019 - Principal investigator: Albanell Mestres, Joan • Comparación de eventos inmunológicos en pacientes con cáncer de pulmón de célula pequeña (CPCP) tratados con quimioterapia estándar vs quimioterapia más ipilimumab - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00591) - Period: from 2017 to 2020 - Principal investigator: Arriola Aperribay, Edurne • Prevenció del càncer colorectal en la población de risc mitjà mitjançant biomarcadors genòmics i microbiòmics (CRIPREV) - Financing institution: Departament de Salut de la Generalitat de Catalunya (SLT002/16/00398) - Period: from 2017 to 2019 - Principal investigator: Montagut Viladot, Clara • Estroma tumoral y terapia personalizada en cáncer de mama y cáncer colorrectal - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00211) - Period: from 2018 to 2020 - Principal investigator: Calon, Alexandre • LCOR orchestrates the differential IFN-a response and immunological properties of triple-negative breast cancer stem cells - Financing institution: Cancer Research Institute (55054) - Period: from 2018 to 2020 - Principal investigator: Celià Terrassa, Antoni See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 69 Cancer Molecular Cancer Therapeutics

Participation in Research Networks

• CIBER Cancer - Financing institution: Fondo de Investigación Sanitaria. ISCIII. CB16/12/00241 - Period: from 2017 to 2019 - Principal investigator: Albanell Mestres, Joan

Clinical Trials Signed in 2019

• Ensayo en fase III, internacional, multicéntrico, aleatorizado, doble ciego y controlado con placebo de durvalumab o durvalumab y tremelimumab como tratamiento de consolidación en pacientes con cáncer de pulmón microcítico con enfermedad limitada en estadio I-III que no han progresado después de un tratamiento concomitante de quimiorradioterapia (ADRIATIC) - Protocol: D933QC00001 - Sponsor: AstraZeneca AB - Budget: 196,004.2 € - Principal investigator: Arriola Aperribay, Edurne • Atezolizumab, pertuzumab y trastuzumab con quimioterapia como tratamiento neoadyuvante en pacientes con cáncer de mama precoz y localmente avanzado HER2 positivo de alto riesgo (APTneo) - Protocol: FM-B01-17 - Sponsor: Fondazione Michelangelo - Budget: 15,725 € - Principal investigator: Servitja Tormo, Sònia • The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN) - Protocol: KO-TIP-007 - Sponsor: Kura Oncology - Budget: 19,832.5 € - Principal investigator: Guix Arnau, Marta • A Phase II, Multicenter, Randomized, Open-Label, Controlled Study of M7824 versus Pembrolizumab as a First‑line Treatment in Patients with PD-L1 Expressing Advanced Non-small Cell Lung Cancer - Protocol: MS200647-0037 - Sponsor: Merck Sharp & Dohme - Budget: 46,570 € - Principal investigator: Arriola Aperribay, Edurne

70 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Molecular Cancer Therapeutics

• Estudio de fase II, internacional, multicéntrico, randomizado y abierto para evaluar la eficacia y la seguridad de la continuación de palbociclib en combinación con terapia endocrina de segunda línea en pacientes con cáncer de mama avanzado con receptores hormonales positivos y HER2 negativo tras beneficio clínico durante el tratamiento de primera línea basado en palbociclib (PALMIRA) - Protocol: MedOPP068 - Sponsor: MedSIR ARO - Budget: 25,675 € - Principal investigator: Servitja Tormo, Sònia • Estudio en fase III, multicéntrico, aleatorizado y abierto para comparar atezolizumab (anticuerpo anti-PD-L1) en combinación con quimioterapia adyuvante basada en antraciclina/taxano frente a solo quimioterapia en pacientes con cáncer de mama triple negativo operable - Protocol: BIG 16-05/AFT-27/WO39391 - Sponsor: F. Hoffman-La Roche - Budget: 66,800 € - Principal investigator: Servitja Tormo, Sònia • Estudio de extensión multicéntrico, abierto en pacientes incluídos previamente en un estudio clínico de atezolizumab promocionado por Genetech y/o F. Hoffmann-La Roche, LTD - Protocol: BO39633 - Sponsor: Roche Farma S.A. - Budget: 13,824 € - Principal investigator: Taus Garcia, Álvaro • BARBICAN: A randomised, open-label Phase II study to determine the contribution of ipatasertib to neoadjuvant chemotherapy plus atezolizumab in women with triple- negative breast cancer - Protocol: 012418QM - Sponsor: Queen Mary University of London - Budget: 17,650 € - Principal investigator: Servitja Tormo, Sònia • Neoadyuvancia con Letrozol y Palbociclib en pacientes con cáncer de mama estadios II-IIIb, Fenotipo RH (+) / HER2 (-) y Recurrence Score (Oncotype-Dx) Intermedio (18- 25) o Alto (>25) con análisis de cambios en el RS a la cirugía - Protocol: MedOPP199_DxCARTES - Sponsor: MedSIR ARO - Budget: 29,500 € - Principal investigator: Servitja Tormo, Sònia

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 71 Cancer Molecular Cancer Therapeutics

• Multicentric phase II clinical trial to evaluate the activity of encorafenib and binimetinib before local treatment in patients with BRAF mutated melanoma with metastasis to the brain - Protocol: GEM-1802 - Sponsor: Grupo Español Multidisciplinar de Melanoma (GEM) - Budget: 9,000 € - Principal investigator: Montagut Viladot, Clara • Estudio en fase III, multicéntrico, aleatorizado, abierto y controlado con principio activo de DS-8201a, un conjugado de fármaco y anticuerpo (CAF) anti-HER2, en comparación con el tratamiento elegido por el médico en sujetos con cáncer de mama irresecable o metastásico (o ambos) con expresión baja de HER-2 - Protocol: DS8201-A-U303 - Sponsor: Daiichi Sankyo Inc - Budget: 42,897 € - Principal investigator: Tusquets Trias de Bes, Ignacio • Estudio de fase 3 de pembrolizumab en combinación con pemetrexed/platino (carboplatino o cisplatino) seguido de pembrolizumab y olaparib de mantenimiento en comparación con pemetrexed de mantenimiento en el tratamiento de primera línea de participantes con cáncer de pulmón no microcítico, de histología no epidermoide, metastásico - Protocol: MK-7339-006 - Sponsor: Merck Sharp & Dohme de España, S.A. - Budget: 391,643 € - Principal investigator: Arriola Aperribay, Edurne • Estudio multicéntrico, doble ciego, aleatorizado y controlado de M7824 con quimiorradioterapia concurrente seguida de M7824 en comparación con quimiorradioterapia concurrente más placebo seguida de durvalumab en participantes con cáncer de pulmón no microcítico irresecable en estadio III - Protocol: MS200647-0005 - Sponsor: Merck KGaA - Budget: 31,857 € - Principal investigator: Arriola Aperribay, Edurne • A phase III randomized study to investigate the efficacy and safety of atezolizumab (anti-PD-L1 antibody) in combination with neoadjuvant anthracycline/nabpaclitaxel based chemotherapy compared with placebo and chemotherapy in patients with primary invasive triple negative breast cancer - Protocol: WO39392 - Sponsor: Roche Farma S.A. - Budget: 34,580 € - Principal investigator: Servitja Tormo, Sònia

72 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Molecular Cancer Therapeutics

• Estudio de fase 2, abierto, de encorafenib + binimetinib en pacientes con cáncer de pulmón no microcítico con mutación BRAFV600E - Protocol: WO39392 - Sponsor: Roche Farma, S.A. - Budget: 34,580 € - Principal investigator: Servitja Tormo, Sònia • Estudio de fase 2, abierto, de encorafenib + binimetinib en pacientes con cáncer de pulmón no microcítico con mutación BRAFV600E - Protocol: ARRAY-818-202 - Sponsor: Array BioPharma Inc. - Budget: 4,639.36 € - Principal investigator: Taus Garcia, Álvaro • Estudio de primera administración en humanos en fase I/Ib de aumento escalonado de la dosis y ampliación de la dosis para evaluar la seguridad, farmacocinética, farmacodinámica y actividad antineoplásica de SAR439459 administrado por vía intravenosa en monoterapia y en combinación con cemiplimab en pacientes adultos con tumores sólidos avanzados - Protocol: TCD14678 - Sponsor: Sanofi-Aventis, S.A. - Budget: 192,650 € - Principal investigator: Bellmunt Molins, Joaquim • Estudio de fase 3, aleatorizado y abierto de pembrolizumab (MK 3475) más lenvatinib (E7080/MK-7902) frente a quimioterapia para el tratamiento de primera línea del carcinoma endometrial avanzado o recurrente (LEAP-001) - Protocol: MK7902-001 /E7080-G000-313/ ENGOT-EN9 - Sponsor: Merck Sharp & Dohme - Budget: 174,954 € - Principal investigator: Taus Garcia, Álvaro • Estudio de fase 3, aleatorizado y abierto de pembrolizumab (MK 3475) más lenvatinib (E7080/MK-7902) frente a quimioterapia para el tratamiento de primera línea del carcinoma endometrial avanzado o recurrente (LEAP-001) - Protocol: ARRAY-818-103 - Sponsor: Array BioPharma, Inc. - Budget: 19,106.25 € - Principal investigator: Martínez García, María

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 73 Cancer Molecular Cancer Therapeutics

• Estudio de fase 3 de pembrolizumab en combinación con etopósido/platino (cisplatino o carboplatino) seguido de pembrolizumab con o sin olaparib de mantenimiento en el tratamiento de primera línea de participantes con cáncer microcítico de pulmón en estadio avanzado (CMP-EA) - Protocol: MK-7339-005 - Sponsor: Merck Sharp & Dohme de España, S.A. - Budget: 237,870 € - Principal investigator: Arriola Aperribay, Edurne • Estudio de fase 1b de ASP8374, un inhibidor de puntos de control inmunitario, en monoterapia y en combinación con pembrolizumab en sujetos con tumores sólidos avanzados - Protocol: 8374-CL-0101 - Sponsor: Astellas Pharma Global Development Inc. - Budget: 61,497.01€ - Principal investigator: Martínez García, María • Estudio en fase III, multicéntrico, aleatorizado, abierto y controlado con principio activo de trastuzumab deruxtecan (DS-8201a), un conjugado de fármaco y anticuerpo anti-HER2, frente al tratamiento de elección del investigador para sujetos con cáncer de mama irresecable y/o metastásico que expresa HER-2 tratados previamente con T-DM1 - Protocol: DS8201-A-U301 - Sponsor: Daiichi Sankyo. Inc. - Budget: 32,774 € - Principal investigator: Servitja Tormo, Sònia

Theses

• Clavé S. Molecular diagnosis of predictive biomarkers in patients with non-small-cell lung carcinoma. Universitat de Barcelona - Directors: Salido Galeote, Marta; Arriola, Edurne - Date of defense: 25/11/2019 • Guardia C. Cancer-associated fibroblasts and response to anti-HER2 monoclonal antibodies in HER2-positive breast cancer. Universitat Pompeu Fabra - Director: Albanell Mestres, Joan; Rovira Guerin, Ana - Date of defense: 19/12/2019

74 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Molecular Cancer Therapeutics

Appointments

• Joan Albanell is member of the Consell Assessor del Pla Director d’Oncologia de Catalunya

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Edurne Arriola. Noves eines contra el càncer. Science Festival 2019 Barcelona. 26 October 2019. • Visit to the Laboratory of Molecular Cancer Therapeutics. Molecular Cancer Therapeutics Research Group. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019. • Students of the IES Vall de Tenes visit the Laboratory of Molecular Cancer Therapeutics Group. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 12 December 2019. • Visit to the Laboratory of Molecular Cancer Therapeutics for students from the Medical Laboratory Technologies of the University College of Ghent in Belgium. 12 November 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 75 Molecular Mechanisms of Cancer and Stemness

> Cancer RESEARCH GROUP

Group Leader Members Lluís Espinosa Blay Josune Alonso Martínez de Marañón (PhD Student) [email protected] Irene Pecharromán Ruiz (PhD Student) Laura Solé Font (PhD Student) Laura Marruecos Aylagas (Technician) Teresa Lobo (Postdoctoral Researcher)

The Molecular Mechanisms of Cancer and Stemness group is fully dedicated to the identification of elements and pathways that regulate Stem Cell and Cancer Stem Cell homeostasis, with the final goal of discovering biomarkers and therapeutic targets for regenerative medicine and cancer. The group has historically focused on studying the Notch and NF-κB pathways, which are principal actors of these processes. However, our research now aims to integrate these pathways in the context of other important signals for stem cell and cell transformation such as BRAF or ß-catenin.

76 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Molecular Mechanisms of Cancer and Stemness

Main Publications

• Colomer C, Margalef P, Villanueva A, Vert A, Pecharromán I, Solé L, González-Farré M, Alonso J, Montagut C, Martínez M, Bertran J, Borrás E, Iglesias M, Sabido E, Bigas A, Boulton S, Espinosa L. IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer. Mol Cell 2019; 75(4): 669-682. IF 14.548. D1. • Bueno C, Calero-Nieto FJ, Wang X, Valdés-Mas R, Gutiérrez-Agüera F, Roca-Ho H, Ayllón V, Real PJ, Arambile D, Espinosa L, Torres-Ruiz R, Agraz-Doblas A, Varela I, de Boer J, Bigas A, Gottgens B, Marschalek R, Menéndez P. Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation between AF4-MLL and MLL-AF4 fusions. Haematologica 2019; 104(6): 1189-1201. IF 7.57. D1. • López-Arribillaga E, Rodilla V, Espinosa L. Could JAG1 protein inhibition prevent colorectal cancer? Future Oncol. 2019; 15(4): 345-347. IF 2.279. Q3. See all Publications

Ongoing Research Projects

• Identificación de nuevos biomarcadores y dianas terapéuticas asociados a la actividad IKK - Funding institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00437) - Period: from 2017 to 2020 - Principal investigator: Espinosa Blay, Lluís See all Projects

Theses

• Laura Marruecos Aylagas. IkBα as an essential player in Intestinal Stem Cell homeostasis. Universitat de Barcelona - Director: Espinosa Blay, Lluís - Date of defense: 26/09/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 77 Poly (ADP-ribose) Polymerases

> Cancer RESEARCH GROUP

Group Leader Members José Yélamos López Laura Regué Barrufet (Researcher) [email protected] Coral Ampurdanés Descals (Technician) Nura Lutfi Royo (Technician) Lucía Moreno-Lama (Technician)

The aim of this group is to investigate the immunomodulatory roles of PARP proteins by using in vivo mouse models, and to investigate the relevance of this immunomodulation in the context of the immune response to cancer.

Main Publications

• Galindo-Campos MA, Bedora-Faure M, Farrés J, Lescale C, Moreno-Lama L, Martínez C, Martín-Caballero J, Ampurdanés C, Aparicio P, Dantzer F, Cerutti A, Deriano L, Yélamos J. Coordinated signals from the DNA repair enzymes PARP-1 and PARP-2 promotes B-cell development and function. Cell Death Differ 2019; 26(12): 2667- 2681. IF 8.086. Q1. • Llinàs-Mallol L, Redondo-Pachón D, Pérez-Sáez MJ, Raïch-Regué D, Mir M, Yélamos J, López-Botet M, Pascual J, Crespo M. Peripheral blood lymphocyte subsets change after steroid withdrawal in renal allograft recipients: a prospective study. Sci Rep 2019; 9(1): 7453. IF 4.011. Q1.

78 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Poly (ADP-ribose) Polymerases

• Echeverri Tirado LC, Ghonim MA, Wang J, Al-Khami AA, Wyczechowska D, Luu HH, Kim H, Sánchez-Pino MD, Yélamos J, Yassin LM, Boulares AH. PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function. Mediators Inflamm 2019; 1656484. IF 3.545. Q2. See all Publications

Ongoing Research Projects

• Modulación de la respuesta inmune por las proteínas PARP en cáncer de mama - Financing institution: Asociación Española Contra el Cáncer (AECC) - Period: from: 2018 to 2020 - Principal investigator: Yélamos López, José • Estudio de las funciones específicas de las proteínas PARP en el stress replicativo inducido por oncogenes y su relevancia en cáncer - Financing institution: Ministerio de Economía y Competitividad (SAF2017- 83565-R) - Period: from 2018 to 2020 - Principal investigator: Yélamos López, José See all Projects

Theses

• Galindo-Campos MA. PARP-1 and PARP-2 coordinate lymphocyte development and function: A consideration for PARP inhibidors in cancer therapy. Universitat de Barcelona - Directors: Yélamos López, José; Martín-Caballero, J - Date of defense: 27/11/2019

Outreach

Conferences, Seminars and Courses

• José Yélamos. Conference: PARP-1/PARP-2 double deficiency in mouse B cells results in impair homeostasis and faulty immune responses. PARP2019 Meeting. Budapest, Hungary. 22 May 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 79 Radiation Oncology

> Cancer RESEARCH GROUP

Group Leader Members Manuel Ignacio Algara López Enric Fernández Velilla-Ceprià (Researcher) [email protected] Palmira Foro Arnalot (Researcher) Òscar Pera Cegarra (Researcher) Jaume Quera Jordana (Researcher) Anna Reig Castillejo (Researcher) Núria Rodríguez de Dios (Researcher) Javier Sanz Latiesas (Researcher) Ismael Membrive Conejo (PhD Student) M. Josefa Dengra Domingo (Technician) Rafael Jiménez Lahuerta (Technician)

The Radiation Oncology Research Group (GREOR) is a clinical and basic research group working on the use of radiation as a base of cancer treatment, especially in the lines of altered fractionation, radiotoxicity and quality of life, technological quality control and innovation; in addition to clinical projects linked to the clinical activity in the Radiation Oncology Service. It is a multidisciplinary group comprising medical staff, physicists, technicians and nursing staff. The group has a significant scientific output in relation to radiation oncology groups in the area, besides activity to give research visibility. Its main objective is to maintain the active lines of research, establish synergies with other groups, both national and international, to continue with the group’s training activities and the level of scientific output, and fundraising for both competitive and

80 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Radiation Oncology

non-competitive funds, besides increasing its impact in society (popular science, clinical practice guidelines, patient groups and dissemination).

Main Publications

• Rodríguez A, Arenas M, Lara PC, López-Torrecilla J, Algara M, Conde A, Pérez-Montero H, Muñoz JL, Peleteiro P, Pérez-Calatayud MJ, Contreras J, Ferrer C, Spanish Society of Oncology and Radiotherapy (SEOR) Analysis Group. Are there enough radiation oncologists to lead the new Spanish radiotherapy? Clin Transl Oncol 2019; 21(12): 1663-1672. IF 2.441. Q3. • Guillén A, Bofill N, Marco E, Pera O, Foro P. Effects of prophylactic swallowing exercises on dysphagia and quality of life in patients with head and neck cancer receiving (chemo) radiotherapy: the Redyor study, a protocol for a randomized clinical trial. Trials 2019; 20(1): 503. IF 1.975. Q3. • Carles J, Gallardo E, Doménech M, Font A, Bellmunt J, Figols M, Mellado B, Sáez MI, Suárez C, Méndez MJ, Maroto P, Luque R, de Portugal T, Aldabo R, Bonfill T, Morales- Barrera R, García J, Macià S, Maldonado X, Foro P. Phase II randomized study of radiotherapy and three-year androgen deprivation with or without concurrent weekly docetaxel in high-risk localized prostate cancer patients. Int J Radiat Oncol Biol Phys 2019; 103(2): 344-352. See all Publications

Ongoing Research Projects

• Valoración de los beneficios de la rehabilitación profiláctica de la musculatura deglutoria sobre la calidad de vida y deglución, a corto y medio plazo, de los pacientes sometidos a radioterapia por cáncer de cabeza y cuello: ensayo clínico aleatorizado - Financing institution: Fundación Asociación Española Contra el Cáncer (PS14152556FORO) - Period: from 2015 to 2019 - Principal investigator: Foro Arnalot, Palmira See all Projects

Awards

• N. Rodríguez, on behalf of GOECP/SEOR-GICOR. Randomized phase III trial of prophylactic cranial irradiation with hippocampla avoidance for small-cell lung cancer (SCLC) Best communication. XX Congress of the Sociedad Española de Oncología Radioterápica (SEOR). Santiago de Compostela, June 2019. • Raquel Carrasco. Award for the best clinical case of the Societat Catalano-Balear d’Oncologia for the 2018-19 academic year.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 81 Stem Cells and Cancer

> Cancer RESEARCH GROUP

Group Leader Members Anna Bigas Salvans Violeta García Hernández (Researcher) [email protected] Yolanda Guillén Montalbán (Researcher) Teresa Lobo Jarne (Researcher) Roshana Thambyrajah (Researcher) David Arambilet Morilla (PhD Student) Luis Galán Palma (Phd Student) Jèssica González Miranda (Technician) Arnau Iglesias Piqueras (Technician)

Our research group studies the molecular mechanisms involved in the generation and maintenance of healthy stem cells and their differentiation to functional cells. We particularly focus in studying signaling pathways and their activation effects that control the hematopoietic system. Our goal is to understand how these signals are important in the generation of hematopoietic stem cells during embryonic development, maintenance of these cells in adulthood and how these signals are perturbed in leukemic processes.

82 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Stem Cells and Cancer

Main Publications

• Colomer C, Margalef P, Villanueva A, Vert A, Pecharromán I, Solé L, González-Farré M, Alonso J, Montagut C, Martínez-Iniesta M, Bertran J, Borràs E, Iglesias M, Sabidó E, Bigas A, Boulton SJ, Espinosa L. IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer. Mol Cell. 2019; 75(4): 669-682. IF 14.548. Q1. See all Publications

Ongoing Research Projects

• Hematopoietic and leukemic stem cell specification - Financing institution: Ministerio de Economía y Competitividad (SAF2016 -75613-R) - Period: from 2017 to 2019 - Principal investigator: Bigas Salvans, Anna • Exploring mechanisms of resistance in adult and paediatric T-Acute Lymphoblastic leukemia - Financing institution: Asociación Española Contra el Cáncer (AECC), Programa de ayuda a grupos estables - Period: from 2016 to 2021 - Principal investigator at IMIM and coordinator: Bigas Salvans, Anna • Hematopoietic regeneration from ES Cells - Financing institution: Generalitat de Catalunya (PERIS-SLT002/16/00299) - Period: from 2017 to 2019 - Principal investigator at IMIM and coordinator: Bigas Salvans, Anna • Human disease modelling of GATA2-related Myelodysplastic Syndromes and Acute Myeloid Leukemia (GATA2-Humo) - Financing institution: EraPerMed, (H2020), Departament de Salut, Generalitat de Catalunya - Period: from 2019 to 2022 - Amount: 942,369 € - Coordinator: Alessandra Giorgetti - Principal investigator at IMIM: Bigas Salvans, Anna See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 83 Cancer Stem Cells and Cancer

Participation in Research Networks

• CIBER Cancer - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB16/12/00244) - Period: from 2017 to 2019 - Principal investigator: Bigas Salvans, Anna

Outreach

Conferences, Seminars and Courses

• Anna Bigas. Invited Speaker. Seminar series DKFZ. Heidelberg, 12 April 2019. • Anna Bigas. Speaker and organizer. IJC Opening Symposium on Genetics and Epigenetics of Leukemia and Lymphoma. Badalona, September 2019. • Anna Bigas. Invited Speaker. The Notch Meeting. Athens, October 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Students of the Centre d’Estudis Montseny visit the Laboratory of the Stem Cells and Cancer Group. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 25 January 2019. • Anna Bigas. What can we do with stem cells and where do we want to get? UniStem Day at the BST (Tissue and Blood Bank), 15 March 2019. • Visit to the Laboratory of the Stem Cells and Cancer Group. Escolab Project. Barcelona Science Programme of the Institute of Culture. 25 January 2019.

84 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Translational Research on Hematological Neoplasms

> Cancer RESEARCH GROUP

Group Leader Members Blanca Espinet Solà Leonor Arenillas Rocha (Researcher) [email protected] Luis Carlos Barranco Sanz (Researcher) Gonzalo Blanco Ares (Researcher) Xavier Calvo González (Researcher) Lluís Colomo Saperas (Researcher) Ana Ferrer del Álamo (Researcher) Fernando Gallardo Hernández (Researcher) Carme Pedro Olivé (Researcher) Anna Maria Puiggros Metje (Researcher) Marta Salido Galeote (Researcher) Sílvia Ramos Campoy (PhD Student) Sergi Clavé Safon (Technician) Beatriz Costán Medina (Technician) M. Carme Melero Vilella (Technician) María del Mar Rodríguez Rivera (Technician)

The Translational Research on Hematological Neoplasms Group (GRETNHE) is integrated within the Cancer Programme from the Hospital del Mar Medical Research Institute (IMIM). The GRETNHE is a multidisciplinary group with different research areas. Among them, the most relevant are myelodysplastic syndromes (MDS), myeloproliferative neoplasms/myelodysplastic syndromes (MPN/MDS), chronic

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 85 Cancer Translational Research on Hematological Neoplasms

lymphocytic leukemia/monoclonal B cell lymphocytosis (CLL/MBL), mantle cell lymphoma/monoclonal asymptomatic lymphocytosis cyclin D1 positive (MCL/MALD1), splenic marginal zone lymphoma (SMZL) and cutaneous lymphomas (CL). Our aim is the phenotypic, cytogenetic and molecular characterization of these entities.

Main Publications

• Baliakas P, Jeromin S, Iskas M, Puiggros A, Plevova K, Nguyen-Khac F, Davis Z, Rigolin GM, Visentin A, Xochelli A, et al. (Espinet B); ERIC, the European Research Initiative on CLL. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood 2019; 133(11): 1205-1216. IF 16.5. Q1. • Martín-García D, Navarro A, Valdés-Mas R, Clot G, Gutiérrez-Abril J, Prieto M, Ribera-Cortada I, Woroniecka R, Rymkiewicz G, Bens S, et al. (Espinet B). CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1(-) mantle cell lymphoma. Blood 2019; 133(9): 940-951. IF 16.5. Q1. • Conde E, Hernández S, Martínez R, Angulo B, de Castro J, Collazo-Lorduy A, Jiménez B, Muriel A, Mate JL, Moran T, et al. (Pijuan L, Salido M, Arriola E). Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Non-Small Cell Lung Carcinoma Patients: the ROSING Study. J Thorac Oncol 2019; 14(12): 2120-2132. IF 12.46. Q1. • Clavé S, Rodon N, Pijuan L, Díaz O, Lorenzo M, Rocha P, Taus Á, Blanco R, Bosch- Barrera J, Reguart N, de la Torre N, Oliveras G, Espinet B, Bellosillo B, Puig X, Arriola E, Salido M. Next-generation Sequencing for ALK and ROS1 Rearrangement Detection in Patients With Non-small-cell Lung Cancer: Implications of FISH-positive Patterns. Clin Lung Cancer 2019; 20(4):e421-e429. IF 4.117. Q2. • Florensa L, Arenillas L, Calvo X, Pérez-Vila E, Montesdeoca S, Ferrer A, Woessner S. The importance of adequate recognition of normal and dysplastic myelopoiesis for the diagnosis of myelodysplastic syndromes. Histol Histopathol 2019; 34(8): 857-873. IF 1.7. Q2. See all Publications

Ongoing Research Projects

• Desarrollo y validación de un panel de secuenciación para translocaciones y mutaciones con relevancia clínica en neoplasias de células B maduras - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00437) - Period: from 2016 to 2020 - Principal investigator: Espinet Solà, Blanca

86 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cancer Translational Research on Hematological Neoplasms

• Leucemia linfática crónica de alto riesgo genético: caracterización citogenético- molecular y epigenética por microarrays y Next Generation Sequencing. Asociación con impacto clínico - Financing institution: Fundación Española de Hematología y Hemoterapia (FEHH) - Period: from 2018 to 2019 - Principal investigator: Blanco Ares, Gonzalo • Análisis clínico de la monitorización mediante genotipado de ADN tumoral circulante en sangre (biopsia líquida) en pacientes con neoplasias linfoides de alto grado - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00313) - Period: from 2018 to 2020 - Principal investigator: Colomo Saperas, Lluís • Clinico-biological characterization of chronic lymphocytic leukemia (CLL) patients with complex karyotype (CK) and absence of TP53 aberrations - Financing institution: Gilead Sciences S.L.U. - Period: from 2018 to 2019 - Principal investigator: Espinet Solà, Blanca See all Projects

Theses

Outreach

Conferences, Seminars and Courses

• Blanca Espinet, Marta Salido, Anna Puiggros, Sergi Clavé, Carme Melero, Maria Rodríguez. VIII Curso de hibridación in situ fluorescente (FISH) en muestras parafinadas. Barcelona, 4-5 June 2019. • Lourdes Florensa, Ana Ferrer, Leonor Arenillas, Xavier Calvo, Carles Barranco. Citología Hematológica para Hematólogos (LXVI edition). Escola de Citologia Hematològica Soledad Woessner-Parc de Salut Mar. Lab. Citologia hematològica. Patologia. 21-25 January 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 87 Cancer Translational Research on Hematological Neoplasms

• Lourdes Florensa, Ana Ferrer, Leonor Arenillas, Xavier Calvo, Carles Barranco. Citología Hematológica en el Diagnóstico Integrado (LXVII edition). Escola de Citologia Hematològica Soledad Woessner-Parc de Salut Mar. Lab. Citologia hematològica. Patologia. 13-17 May 2019. • Lourdes Florensa, Ana Ferrer, Leonor Arenillas, Xavier Calvo, Carles Barranco. Citología Hematológica en el Diagnóstico Integrado (LXVIII edition). Escola de Citologia Hematològica Soledad Woessner-Parc de Salut Mar. Lab. Citologia hematològica. Patologia. 18-22 November 2019. • Lourdes Florensa, Ana Ferrer, Leonor Arenillas, Xavier Calvo. La citología en el diagnóstico de los síndromes mielodisplásicos. Escola de Citologia Hematològica Soledad Woessner-Parc de Salut Mar. Lab. Citologia hematològica. Patologia. 2-3 October 2019.

88 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY

Programmes

Epidemiology and Public Health

10 115 38 258 Research Professionals Research Publications groups projects

Programme Directors Jordi Alonso Caballero Jaume Marrugat de la Iglesia

RESEARCH GROUPS Research Group in Nursing Care Silvia Esteban Barcelona Research Infertility Group Miguel Ángel Checa Social Epidemiology and Occupational Health Consol Serra Cardiovascular Epidemiology and Genetics Roberto Elosua

Cardiovascular Risk and Nutrition ASSOCIATED GROUPS Montserrat Fitó Healthy Cities and Environmental Justice Clinical and Molecular Epidemiology of Cancer Isabelle Anguelovski Miquel Porta

Epidemiology and Evaluation Maria Sala

Girona Heart Registry Jaume Marrugat

Health Services Jordi Alonso

90 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Programme

The Epidemiology and Public Health Programme (EPISAP) is formed by 10 research groups and has approximately 120 members. Our mission is to apply advanced epidemiologic methods for a better understanding of: a) the individual and societal burden of disease; b) major risk factors and underlying mechanisms; and c) the role of health services and interventions on health outcomes. Our research focuses on cancer, cardiovascular diseases, mental disorders, and on environmental and occupational exposures. We translate our research into public health and clinical practice and we innovate in the preventive and health care assessment fields.

Outstanding scientific achievements in 2019

• Anguelovski I, Connolly J, Pearsall H, et al. Why green “climate gentrification” threatens poor and vulnerable populations. PNAS 2019; 116 (52): 26139-43. • Román M, Hofvind S, von Euler-Chelpin M, Castells X. Long-term risk of screen- detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts. Br J Cancer 2019; 120(2): 269-275. • Sayón-Orea C, et al. Effect of a Nutritional and Behavioral Intervention on Energy- Reduced Mediterranean Diet Adherence Among Patients with Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial. JAMA 2019; 322(15): 1486-99. EPISAP researchers directed 10 PhD theses defended in 2019, and obtained competitive funding for 6 national research projects, one H2020 project, one intensification grant, and 6 private contracts.

Impact of our research in 2019

• Programme researchers have co-authored the European Guides for Screening and Diagnosis of Breast Cancer (EC Initiative on Breast Cancer). • Jordi Alonso received the Presidential Award from the International Society for Quality of Life Research (ISOQOL) for his contribution to the advancement of research into Health-Related Quality of Life.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 91 Barcelona Research Infertility Group

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Miguel Ángel Checa Vizcaino Mireia González Comadrán (Researcher) [email protected] Maria Prat Om (Researcher) Ana Beatriz Robles Corchado (Researcher)

Biomedical care in fertility disorders has gained recognition as has the diagnosis and treatment of a disease, infertility, where an essential biological function to achieve a life plan is impaired. Taking this into consideration, since 1995, the diagnosis and treatment of infertility has been included as a basic benefit within the Catalog of Services of the National Health System (Royal Degree 63/1995, 20 January, health benefits under the social security program). The overall objective is to carry out research in a multidisciplinary group, and to combine collective expertise to extend knowledge of the loss of fertility observed in our society, as well as to offer preventive, diagnostic and therapeutic solutions that will either minimize the impact of this disorder or successfully overcome it. Epidemiological research aims to analyze various air pollutants and environmental factors and assess their impact on reproductive outcomes, including sperm quality, which may lead to guidelines for the prevention or reduction of human exposure to environmental pollutants. Clinical research in human model will allow us to assess strategies that may potentially improve reproductive functions and thereby increase live birth rate when ART are required.

92 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Barcelona Research Infertility Group

Evidence Based Medicine research: We collaborate with the Cochrane Gynecology and Fertility group evaluating the evidence in reproductive medicine in international studies. We aim to develop translational recommendations for best clinic practice.

Main Publications

• Bellver J, Bosch E, Espinós JJ, Fabregues F, Fontes J, García-Velasco J, Llácer J, Requena A, Checa MA; Spanish Infertility SWOT Group (SISG). Second-generation preimplantation genetic testing for aneuploidy in assisted reproduction: a SWOT analysis. Reprod Biomed Online 2019; 39(6): 905-915. IF 2.930. Q1. • Moreno-Sepúlveda J, Checa MA. Risk of adverse perinatal outcomes after oocyte donation: a systematic review and meta-analysis. J Assist Reprod Gen 2019; 36(10): 2017-2037. IF 2.820. Q1. • Mañé L, Flores-Le Roux JA, Pedro-Botet J, Gortázar L, Chillarón JJ, Llauradó G, Payà A, Benaiges D. Is fasting plasma glucose in early pregnancy a better predictor of adverse obstetric outcomes than glycated haemoglobin? Eur J Obstet Gynecol Reprod Biol 2019; 234: 79-84. IF 2.024. Q3. • Mañé L, Flores-Le Roux JA, Benaiges D, Chillarón JJ, Prados M, Pedro-Botet J, Llauradó G, Gortázar L, Payà A. Impact of overt diabetes diagnosed in pregnancy in a multi-ethnic cohort in Spain. Gynecol Endocrinol 2019; 35(4): 332-336. IF 1.406. Q4. See all Publications

Participation in Research Networks

• CIBER Cancer - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB16/12/00244) - Period: from 2017 to 2019 - Principal investigator: Bigas Salvans, Anna

Clinical Trials Signed in 2019

• Ensayo clínico fase III, aleatorizado, abierto, multicéntrico y de grupos paralelos para la detección, en segundo trimestre del embarazo, de los falsos positivos del cribado de preeclampsia de primer trimestre (StopPRE) - Sponsor: Fundació Institut Recerca Hospital Vall d’Hebron - Budget: No economic compensation - Principal investigator: Prat Om, Maria

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 93 Epidemiology and Public Health Barcelona Research Infertility Group

Theses

• Lattes K. Resultados reproductivos en mujeres sometidas a ciclos de fecundación in vitro en fresco versus ciclos segmentados (freeze-all). Universitat Autònoma de Barcelona - Directors: Checa Vizcaíno, Miguel Ángel; Vassena, R - Date of defense: 11/07/2019 • Moreno JA. Impacto de los tratamientos de reproducción asistida sobre los resultados maternos y perinatales. Universitat Autònoma de Barcelona - Directors: Checa Vizcaíno, Miguel Ángel; Moreno, JA - Date of defense: 19/09/2019 • Vidal M. Resultats perinatals en tècniques de reproducció assistida. Estudi de la cohort catalana. Universitat Autònoma de Barcelona - Directors: Checa Vizcaíno, Miguel Ángel; Carreras Collado, Ramón - Date of defense: 23/05/2019

Outreach

Conferences, Seminars and Courses

• Miguel Ángel Checa, organizer. Ist International Symposium on Diet, Lifestyle and Fertility. PRBB. Barcelona, 29 November 2019.

94 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cardiovascular Epidemiology and Genetics

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Roberto Elosua Llanos Albert Clarà Velasco (Researcher) [email protected] María Grau Magaña (Researcher) Alina Velescu (Researcher) Maria del Mar Vila Muñoz (PhD Student) Marta Cabañero Marimon (Technician) Alba Fernández Sanlés (Technician) Isaac Subirana Cachinero (Technician) Esmeralda Gómez Pires (Research Assistant)

The group focuses on the study of the epidemiology and genetic basis of cardiovascular disorders and their risk factors. The group participates in international consortia using genome-wide and exome sequencing approaches to identify common and rare genetic variants associated with cardiovascular traits. We are also interested in the study of epigenetic signatures, mainly DNA methylation, related to these diseases. The research team comprises a multidisciplinary group of epidemiologists, biologists, biochemists, clinicians and biostatisticians who work together to tackle these topics. We use this knowledge to identify new mechanisms and new predictive biomarkers of cardiovascular risk, and to define instrumental variables to assess the causal relationship between a biomarker and a cardiovascular phenotype.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 95 Epidemiology and Public Health Cardiovascular Epidemiology and Genetics

The members of the group also participate in the REGICOR (REgistre GIroní del COR) study to determine the burden of cardiovascular disease and its risk factors at the population level, and to develop and improve cardiovascular risk functions. We are also actively exploring the dose-response relationship between physical activity and cardiovascular disease, and the mechanisms by which physical activity reduces cardiovascular risk. Finally, we are also exploring, developing and evaluating new approaches to improve cardiovascular prevention by using new information-technology tools.

Main Publications

• Grau M. Lipid parameter thresholds: The debate continues. Eur J Prev Cardiol 2019;26(14):1493–1495. IF 5.64. Q1. • Subirana I, Fernández Avilés F, Elosua R, Lidón RM, García-Dorado D, Marrugat J; investigadores del estudio ATHOS. Interhospital Variability in Acute Coronary Syndrome Management in the ATHOS Study. Rev Esp Cardiol (Engl Ed) 2019; 72: 691-693. IF 5.126. Q1. • Sayols-Baixeras S, Fernández-Sanlés A, Prats-Uribe A, Subirana I, Plusquin M, Künzli N, Marrugat J, Basagaña X, Elosua R. Association between long-term air pollution exposure and DNA methylation: The REGICOR study. Environ Res 2019; 176: 108550. IF 5.026. Q1. • De Gonzalo-Calvo D, Elosua R, Vea A, Subirana I, Sayols-Baixeras S, Marrugat J, Llorente-Cortés V. Soluble low-density lipoprotein receptor-related protein 1 as a biomarker of coronary risk: Predictive capacity and association with clinical events. Atherosclerosis 2019; 287: 93-99. IF 4.255. Q1. • Fa-Binefa M, Clará A, Pérez-Fernández S, Grau M, Dégano IR, Martí-Lluch R, Ramos R, Marrugat J, Elosua R. Early smoking-onset age and risk of cardiovascular disease and mortality. Prev Med 2019; 124: 17-22. IF 3.499. Q1. See all Publications

Ongoing Research Projects

• Eficacia de una aplicación móvil para la prevención de las enfermedades cardiovasculares a través del empoderamiento individual y comunitario - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00250) - Period: from 2018 to 2020 - Principal investigator: Grau Magaña, María

96 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Cardiovascular Epidemiology and Genetics

• Seguiment de la cohort poblacional de l’estudi REGICOR: tendències en la incidència de malaltia cardiovascular, en la prevalença de factors de risc, identificació de nous mecanismes i biomarcadors predictius, i avaluació d’estratègies de prevenció - Financing institution: Departament de Salut, Generalitat de Catalunya (SLT002/16/00088) - Period: from 2017 to 2019 - Principal investigator: Elosua Llanos, Roberto See all Projects

Participation in Research Networks

• CIBER Enfermedades Cardiovasculares - Fondo de Investigación Sanitaria. ISCIII (CB16/11/00246) - Principal investigators: Elosua Llanos, Roberto; Clará Velasco, Albert; Velescu, Alina • CIBER Epidemiología y Salud Pública - Fondo de Investigación Sanitaria. ISCIII (CB06/02/0029) - Principal investigator: Grau Magaña, María

Clinical Trials Signed in 2019

• Preparación e implementación del protocolo del estudio “Ensayo clínico abierto, no aleatorizado en dos conglomerados constituidos por dos poblaciones urbanas distintas, compartivo de una intervención preventiva con un grupo control sin intervención sobre el control de factores de riesgo cardiovascular. Healthy Communities”. - Fundació Privada SHE - Principal investigator: Elosua Llanos, Roberto

Theses

• Sayols-Baixeras S. DNA methylation and its relationship with lifestyle, environmental and cardiovascular risk factors. Universitat Pompeu Fabra - Director: Elosua Llanos, Roberto; Lluís-Ganella, C - Date of defense: 18/02/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 97 Epidemiology and Public Health Cardiovascular Epidemiology and Genetics

• Vázquez Oliva, G. El síndrome coronario agudo: tendencias en la magnitud del problema, en el manejo hospitalario y en la aparición de complicaciones en un estudio de base poblacional y mejoras en las estrategias de prevención individual. Universitat de Girona - Director: Elosua Llanos, Roberto - Date of defense: 08/02/2019

Awards

• María Grau Magaña. Prize for the best publication in primary care. Col·legi Oficial de Metges de Barcelona. 27/11/2019. • Roberto Elosua Llanos. Second prize for the most cited long-term article in Revista Española de Cardiología 2019. Sociedad Española de Cardiología (SEC). 18/10/2019.

Appointments

• Roberto Elosua Llanos. Professor of Medicine. Universitat de Vic-Universitat Central de Catalunya. Date: 12/07/2019.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Roberto Elosua Llanos, María Grau Magaña, Alba Fernández Sanlés. Workshop Mesure your cardiovascular health. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019. • Roberto Elosua Llanos. Excursion through the different stages of a research project. Students of the Secretary Coloma Institute visit the Laboratory of Cardiovascular Epidemiology and Genetics Group. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 21 March 2019.

98 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cardiovascular Risk and Nutrition

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Montserrat Fitó Colomer David Benaiges Boix (Researcher) [email protected] Olga Castañer Niño (Researcher) Juan José Chillarón Jordán (Researcher) Juana Antonia Flores Le Roux (Researcher) Albert Goday Arno (Researcher) Camille Lassale (Researcher) Gemma Llauradó Cabot (Researcher) Helmut Schröder (Researcher) Montserrat Villatoro Moreno (Researcher) Albert Sanllorente Melenchón (PhD Student) Gemma Blanchart Cuella (Technician) Daniel Muñoz Aguayo (Technician) Ana Isabel Quindós Sendino (Technician) María Dolores Zomeño Fajardo (Technician) Anna Maria Blasco Lapuente (Research Assistant)

The Mediterranean diet, its foods and the interaction of its nutrients, have healthy effects on morbidity and mortality related to chronic degenerative diseases, such as cardiovascular disease. In this context, the main objective of our research is to determine the benefit of a healthy diet pattern and some characteristic foods (including olive oil and wine) on different cardiovascular risk factors. We also focus on lifestyle habits including diet and

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 99 Epidemiology and Public Health Cardiovascular Risk and Nutrition

physical activity on obesity (both in children and adults), diabetes, and cardiovascular diseases. The health effects of bariatric surgery on cardiovascular risk factors and cardiometabolic diseases, are also among our aims. Based on the knowledge of underlying mechanisms beyond the diet benefits, progress is being made in research of the classical and emerging risk factors for cardiovascular and neurodegenerative diseases. One of our main research lines is focused on HDL and ApoB-containing particles. Firstly, it is becoming increasingly more accepted that the biological functions of HDL are more indicative of the cardioprotective role of these particles than the quantity of HDL cholesterol. Reduced values of the most relevant HDL function (its ability to pick up cholesterol from peripheral cells, the cholesterol efflux) have been shown to be linked to a high risk of sub-clinical atherosclerosis and high incidence of coronary events. Our group was the first to report the protective effect of a healthy dietary pattern (a Mediterranean Diet enriched with virgin olive oil) and real-life doses of virgin olive oil on HDL functions. Secondly, we are also interested in the residual risk factor linked to the atherogenicity of ApopB-containing particles such as LDL and triglyceride-rich lipoproteins.

Main Publications

• Hernáez A, Sanllorente A, Castañer O, Martínez-González MÁ, Ros E, Pintó X, Estruch R, Salas-Salvadó J, Corella D, Alonso-Gómez ÁM, Serra-Majem L, Fiol M, Lapetra J, Gómez-Gracia E, de la Torre R, Lamuela-Raventós RM, Fitó. M. Increased Consumption of Virgin Olive Oil, Nuts, Legumes, Whole Grains, and Fish Promotes HDL Functions in Humans. Mol Nutr Food Res 2019; 63(6): e1800847. IF 4.653. D1. • Cárdenas-Fuentes G, Subirana I, Martínez-González MA, Salas-Salvadó J, Corella D, Estruch R, Fitó M, Muñoz-Bravo C, Fiol M, Lapetra J, Aros F, Serra-Majem L, Tur JA, Pinto X, Ros E, Coltell O, Díaz-López A, Ruiz-Canela M, Schröder H. Multiple approaches to associations of physical activity and adherence to the Mediterranean diet with all-cause mortality in older adults: the PREvención con DIeta MEDiterránea study. Eur J Nutr 2019; 58(4): 1569-1578. IF 4.449. Q1. • Farràs M, Arranz S, Carrión S, Subirana I, Muñoz D, Blanchart G, Kool M, Solà R, Motilva MJ, Escolà-Gil JC, Rubió L, Fernández-Castillejo S, Pedret A, Estruch R, Covas MI, Fitó M, Hernáez A, Castañer O. A Functional Virgin Olive Oil Enriched with Olive Oil and Thyme Phenolic Compounds Improves the Expression of Cholesterol Efflux- Related Genes: A Randomized, Crossover, Controlled Trial. Nutrients 2019; 11(8): E1732. IF 4.171. Q1. • Julià H, Benaiges D, Mollà P, Pedro-Botet J, Villatoro M, Fontané L, Ramon JM, Climent E, Flores Le Roux JA, Goday A. Changes in Thyroid Replacement Therapy after Bariatric Surgery: Differences between Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy. Obes Surg 2019; 29(8): 2593-2599. IF 3.603. Q1. See all Publications

100 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Cardiovascular Risk and Nutrition

Ongoing Research Projects

• Integridad neurovascular y desarrollo de demencia: Efecto neuroprotector de las lipoproteínas de alta densidad y marcadores asociados - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00214) - Period: from 2018 to 2020 - Principal investigator: Castañer Niño, Olga • Efecto de intervenciones sobre el estilo de vida, basadas en dieta y actividad física, sobre la dislipemia aterogénica en pacientes con síndrome metabólico - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00020) - Period: from 2019 to 2021 - Principal investigator: Fitó Colomer, Montserrat • Ensayo clínico controlado con grupos paralelos para evaluar el efecto in vivo del pan EliasBoulanger de larga fermentación (pan EBLF) comparado con pan industrial de corta fermentación (pan CF) en pacientes con síndrome metabólico - Financing institution: Agencia Estatal de Investigación. Convocatoria RETO- Colaboración - Period: from 2018 to 2020 - Principal investigator: Fitó Colomer, Montserrat • Microbiota intestinal como mecanismo implicado en el efecto “halo” en familiares de pacientes con obesidad grave - Financing institution: Societat Catalana d’Endocrinologia i Nutrició - Period: from 2019 to 2020 - Principal investigator: Goday Arno, Albert See all Projects

Participation in Research Networks

• CIBEROBN: Fisiopatología de la Obesidad y Nutrición - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB06/03/0028) - Period: from 2013 - Principal investigator: Fitó Colomer, Montserrat • CIBERESP: Fisiopatología de Salud Pública y Epidemiología - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB06/03/0028) - Period: from 2013 - Principal investigator: Schröder, Helmut

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 101 Epidemiology and Public Health Cardiovascular Risk and Nutrition

Theses

• Soria-Florido MT. Role and predictive value of the HDL function for cardiovascular disease in a high risk population. HDL function-linked markers and mechanisms. Universitat de Barcelona - Director: Fitó Colomer, Montserrat - Date of defense: 11/01/2019 • Parri A. Influencia de la educación nutricional, hábitos de estilo de vida obesogénicos y predictores de pérdida de peso en pacientes con obesidad grave incluidos en un programa de cirugía bariátrica. Universitat de Barcelona - Director: Goday Arno, Albert - Date of defense: 13/11/2019 • Cárdenas-Fuentes G. Association of physical activity with cardiovascular risk factors and all-cause mortality in older Spanish individuals. Universitat Pompeu Fabra - Director: Schröder, Helmut - Date of defense: 24/04/2019

Awards

• PREDIMEDPlus Team (IP: Montserrat Fitó Colomer). Second prize “NAOS Strategy Award to all PREDIMED-PLUS” Team within the Health Sector. Agencia Española de Seguridad Alimentaria y Nutrición. 2019.

Outreach

Conferences, Seminars and Courses

• Montserrat Fitó Colomer. Session group: Gastronomy: great driver of fish consumption. Forum pesca dieta mediterránea. Organització de Productors Pesquers de Sant Carles de la Ràpita and Confraria de Pescadors Verge del Carme de Sant Carles de la Ràpita, in collaboration with Ajuntament de Sant Carles de la Ràpita and Fundació Dieta Mediterrània. Sant Carles de la Ràpita, 4-5 April 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Montserrat Fitó Colomer. Health benefits of the Mediterranean diet: Myth or reality? Closing speech of the Curs de Nutrició del programa Bojos per la Ciència. Hospital Universitari de Bellvitge, 30 November 2019. • Workshop on Mediterranean Diet and Cardiovascular Risk. CARIN Group. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019.

102 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Cardiovascular Risk and Nutrition

• Montse Fitó, Dolors Zomeño, Alejandra Pérez, Olga Castañer, Dani Muñoz, Helmut Schröder. Open seminar to the altruistic public of the call regarding the current project of “La Marató TV3”. 19 March and 21 May 2019. • Nutritional session and the Nutriscore for the PRBB Staff. Health week at the Parc de Recerca Biomèdica de Barcelona (PRBB). 8-17 November 2019. • Montse Fitó, Dani Muñoz, Albert Sanllorente. Excursion through the different stages of a research project. Students of the Secretary Coloma Institute visit the Laboratory of Cardiovascular Risk and Nutrition Group. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 21 March 2019. • Theatre play organized by the CARIN Group for nutritional advice and lifestyle for the PREDIMEDplus Study participants. October 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 103 Clinical and Molecular Epidemiology of Cancer

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Miquel Porta Serra Immaculada Collet Diví (Technician) [email protected] Magda Gasull Panadès (Technician) José Antonio Pumarega Rodríguez (Technician) Yolanda Rovira Pons (Research Assistant)

We conduct integrative scientific research on human pancreatic cancer at all causal and mechanistic levels, from genomics to clinical medicine to the social and physical environment. Our aim is to achieve an optimal integration of professional cultures, scientific knowledge, methodologies and techniques from epidemiology and public health, clinical medicine and the biological sciences. We are a team that has worked across disciplines for more than three decades, one of the pioneer groups in Europe on clinical and molecular epidemiology. Cancer is a complex set of processes that result from the accumulation of genetic, epigenetic and other alterations during the lifecourse. Thus, integrative studies on the causes of cancer are a natural meeting point between molecular biology and epidemiology. We are also a world-recognized research group on the biomonitoring of internal body concentrations of environmental chemical agents (‘internal contamination’) in representative samples of the general population.

104 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Clinical and Molecular Epidemiology of Cancer

Main Publications

• Camargo J, Pumarega J, Alguacil J, Sanz-Gallén P, Gasull M, Delclos GL, Amaral AF, Porta M. Toenail concentrations of trace elements and occupational history in pancreatic cancer. Environ Int 2019; 127: 216-225. IF 7.943. Q1. • Gasull M, Pumarega J, Kiviranta H, Rantakokko P, Raaschou-Nielsen O, Bergdahl IA, et al. Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. Environ Res 2019; 169: 417-433. IF 5.026. Q1. • Porta M, Vandenberg LN. There are good clinical, scientific, and social reasons to strengthen links between biomedical and environmental research. J Clin Epidemiol 2019; 111: 124-126. IF 4.65. Q1. • Llorente C, Revuelta G, Carrió M, Porta M. Scientists’ opinions and attitudes towards citizens’ understanding of science and their role in public engagement activities. PLoS One 2019; 14(11): e0224262. IF 2.776. Q2. • Gómez-Tomás Á, Pumarega J, Alguacil J, Amaral AFS, Malats N, Pallarès N, Gasull M, Porta M; PANKRAS II Study Group. Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma. Environ Mol Mutagen 2019; 60(8): 693-703. IF 2.528. Q2. See all Publications

Ongoing Research Projects

• Influencia de las concentraciones de compuestos tóxicos persistentes sobre la mortalidad, la incidencia de trastornos crónicos y la expresión de miARN en población general - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00088) - Period: from 2017 to 2020 - Principal investigator: Porta Serra, Miquel See all Projects

Participation in Research Networks

• CIBERESP: Epidemiología y salud pública - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB06/02/0034) - Period: from 2006 to 2019 - Principal investigator: Porta Serra, Miquel

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 105 Epidemiology and Public Health Clinical and Molecular Epidemiology of Cancer

• NCD Risk Factor Collaboration (NCD-RisC) - Financing institution: NCD Risk Factor Collaboration (NCD-RisC) (13078) - Period: from 2014 - Principal investigator: Porta Serra, Miquel • European Prospective Investigation into Cancer and Nutrition (EPIC) - Financing institution: IARC (13080) - Period: from 2014 - Principal investigator: Porta Serra, Miquel • Pancreatic Cancer Case-Control Consortium (PanC4) - Financing institution: Pancreatic Cancer Case-Control Consortium (PanC4) (13079) - Period: from 2014 - Principal investigator: Porta Serra, Miquel

Theses

• Gasull M. Anàlisi de la contaminació de la població general per compostos tòxics persistents i d’alguns dels seus efectes adversos per a la salut. Universitat Autònoma de Barcelona - Director: Porta Serra, Miquel - Date of defense: 27/11/2019

Appointments

• Miquel Porta. Adjunct Professor, Center for the Investigation of Environmental Hazards, Department of Pediatrics, New York University (NYU). December 2019.

Outreach

Conferences, Seminars and Courses

• Miquel Porta Serra. Workshop “Anthropocene and Public Health”. Max Planck Institute for the History of Science. Berlin, October 2019. • Miquel Porta Serra. CEHS Special Cancer and Environmental Epidemiology Seminar. University of North Carolina at Chapel Hill. North Carolina, October 2019. • Miquel Porta Serra. Methodological Issues in a Prospective Study on Organic Pollutants and Pancreatic Cancer Risk. University of North Carolina at Chapel Hill. North Carolina, October 2019.

106 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Clinical and Molecular Epidemiology of Cancer

• Miquel Porta Serra. Methodological Issues in a Prospective Study on Organic Pollutants and Pancreatic Cancer Risk. Harvard University, October 2019. • Miquel Porta Serra. Internal Contamination of Human Bodies from Toxic Chemicals: What are the Relevant Frames of Thought? Langone Health, Division of Environmental Pediatrics. October 2019. • Miquel Porta Serra. A prospective European Study on Persistent Pollutants and Pancreatic Cancer Risk. Participation in the Environmental Public Health seminar. Columbia University, NYC. November 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Miquel Porta Serra. Epidemiology seminar on Biomedical Writing. Universidad de Santiago de Compostela. January 2019. • Miquel Porta Serra. Nuestra contaminación interna por residuos de plásticos y otros compuestos ambientales. Ateneu de Maó, November 2019. • Miquel Porta Serra. Aliments Salud i Tòxics. Universitat de Vic. December 2019. • Miquel Porta Serra, Magda Gasull Panadès, Jose Pumarega Rodríguez. Collaboration with the REZERO campaign “Salut de plàstic”. 2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 107 Epidemiology and Evaluation

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Maria Sala Serra Andrea Buron Pust (Researcher) [email protected] Xavier Castells Oliveres (Researcher) Mercè Comas Serrano (Researcher) Francesc Cots Reguant (Researcher) Laia Domingo Torrell (Researcer) Francesc Assís Macià Guilà (Researcher) Margarita Posso Rivera (Researcher) Anna Renom Guiteras (Researcher) Marta Román Expósito (Researcher) Roser Terradas Robledo (Researcher) Cristina Hernández Rodríguez (Technician) Anna Jansana Riera (Technician) Diego Juárez Rodríguez (Technician) Javier Louro Aldamiz-Echevarría (Technician) Pietro Chiarello (Research Assistant) Irene Fernández García (Research Assistant) Priscila Giraldo Matamoros (Research Assistant) Esther Martínez Amor (Research Assistant)

This is a group with multidisciplinary training (epidemiology, health economy, statistics and nursing), which has carried out research activity in the field of health services research (HSR), specifically in the evaluation of the effectiveness and costs of health services and interventions; the evaluation of the needs and use of health services; and

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the development of instruments for HSR. Current research areas focus mainly on the evaluation of the health care process in cancer patients, focusing on breast and colon cancer screening, also using real world data, and the impact of the process on survival, specifically in the study of cancer screening personalization and on health care of long- term survivors. The group is recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a research group in epidemiology and evaluation (2017 SGR 213; from 2018 to 2021; Principal investigator: Xavier Castells Oliveres).

Main Publications

• Burón A, Román M, Augé JM, Macià F, Grau J, Sala M, Louro J, Martínez-Alonso M, Álvarez C, Andreu M, Bessa X, Zaffalon D, Castells A, Pellisé M, Aldea M, Rivero L, Hernández C, Torá-Rocamora I, Castells X. Changes in FIT values below the threshold of positivity and short-term risk of advanced colorectal neoplasia: Results from a population-based cancer screening program. Eur J Cancer 2019; 107: 53-59. IF 6.68. Q1. • Louro J, Posso M, Hilton Boon M, Román M, Domingo L, Castells X, Sala M. A systematic review and quality assessment of individualised breast cancer risk prediction models. Br J Cancer 2019; 121(1): 76-85. IF 5.416. Q1. • Román M, Hofvind S, von Euler-Chelpin M, Castells X. Long-term risk of screen- detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts. Br J Cancer 2019; 120(2): 269-275. IF 5.416. Q1. • Jansana A, Posso M, Guerrero I, Prados-Torres A, Del Cura M, Castells X, Sala M. Health care services use among long-term breast cancer survivors: a systematic review. J Cancer Surviv 2019; 13(3): 477-493. IF 3.585. Q2. • Román M, Sala M, Baré M, Posso M, Vidal C, Louro J, Sánchez M, Peñalva L, Castells X, BELE study group. Changes in mammographic density over time and the risk of breast cancer: An observational cohort study. Breast 2019; 46: 108-115. IF 3.494. Q1. See all Publications

Ongoing Research Projects

• Estimating individual breast cancer risk according to women’s known risk factors for personalised population-based mammographic screening - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00047) - Period: from 2018 to 2020 - Principal investigator: Román Expósito, Marta

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 109 Epidemiology and Public Health Epidemiology and Evaluation

• Evaluation of the sequential pattern of faecal occult blood and its relationship with the risk of colorectal neoplasia: towards the optimization of population-based colorectal cancer screening programs - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00239) - Period: from 2017 to 2019 - Principal investigator: Burón Pust, Andrea • Comorbidity and patterns of heald care use in women who have survived a breast cancer for at least five years - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00244) - Period: from 2017 to 2019 - Principal investigator: Sala Serra, Maria • Benign breast disease, breast density and association with breast cancer in a population-based breast cancer screening program - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00098) - Period: from 2016 to 2020 - Principal investigator: Castells Oliveres, Xavier • Randomized, comparison of risk-stratified versus standard breast cancer screening In European women aged 40-74 - Financing institution: European Commission (Topic D: SC1-PM-10-2017) - Period: from 2018 to 2025 - Principal investigators: Castells Oliveres, Xavier; Román Expósito, Marta See all Projects

Participation in Research Networks

• Research network on health services in chronical diseases – REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas) - Fondo de Investigación Sanitaria. ISCIII. Subprograma RETICS (RD12/0001/0015) - Period: from 2017 to 2021 - Principal investigator: Sala Serra, Maria • Breast Cancer Screening Guidelines Development Group - Financing institution: European Commission Initiative on Breast Cancer (ECIB) - Period: from 2015 to 2020 - Principal investigator: Castells Oliveres, Xavier

110 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Epidemiology and Evaluation

Awards

• Javier Louro García-Aldámiz. XV Research Grant “Alicia Llacer” for young researchers. Sociedad Española de Epidemiología, SEE. 2019 • Anna Jansana. Award for research on breast cancer survivors to the work “Use of health services and comorbidities in long-term breast cancer survivors: protocol of the SURBCAN project”. The 10 best oral communications in the XXXIX Congress of the Spanish Society of Family and Community Medicine (semFYC). Málaga, 8-10 May 2019.

Appointments

• Andrea Burón Pust. Member of the Steering Committee. International Cancer Screening Network, (ICSN). 2019

Outreach

Conferences, Seminars and Courses

Events • Francesc Macià Guilà. Event organiser and coordinator of the Scientific Committee. XXII Workshop on Breast Cancer: What about after cancer? Chronicity and quality of life of patients after breast cancer. Hospital del Mar, Barcelona, 22 March 2019. • Maria Sala. Member of the Scientific and Organisational Committee. VII REDISSEC Workshop: Towards research with an impact on society. REDISSEC (Research network on health services in chronical diseases). Barcelona, 7 November 2019. • Andrea Burón, Xavier Castells, Francesc Macià. Speakers and members of the Scientific Committee. Workshop 10 years preventing colon and rectal cancer in Barcelona. Colon and Rectal Cancer Early Detection Program, Health Department, Generalitat de Catalunya. Barcelona, 13 December 2019. Lectures • Xavier Castells. Critical reflections: Is it time to propose changes in the Programs by establishing more personalized approaches? Breast image update workshop. Sociedad Española de Diagnóstico por Imagen de la Mama (SEDIM). Madrid, February 2019. • Maria Sala. Projects to improve the quality of healthcare in the Parc de Salut Mar Quality Programme: involve and evaluate. Innovation in process improvement: challenges and opportunities. ITEMAS Meeting. Parc Taulí, Sabadell, 11 Desember 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 111 Epidemiology and Public Health Epidemiology and Evaluation

• Andrea Burón. Where are we? Workshop 10 years preventing colon and rectal cancer in Barcelona. Colon and Rectal Cancer Early Detection Program, Health Department, Generalitat de Catalunya. Barcelona, 13 December 2019. Presentations • Vernet-Tomas MM, Louro J, Román M, Saladie F, Posso M, Prieto M, Vázquez I, Baré M, Peñalva L, Vidal C, Bargalló X, Sánchez M, Ferrer J, Espinàs JA, Quintana MJ, Rodríguez-Arana A, Castells X. Le risque de diagnostiguer un càncer pendant les deux ans qui suivent une biopsie benigne du sein est relié à l’image décrite en mammographie qui a subi la biopsie. 41es Journées de la Société Française de Sénologie et de Pathologie Mammaire. Marseille, 6-8 November 2019. • Posso M, Louro J, Román M, Domingo L, Castells S, Sala M. Individualized breast càncer risk prediction models in average-risk women: a systematic review and quality assessment. International Cancer Screening Conference. Rotterdam, The Netherlands, 3-5 June 2019. • Román M, Domingo L, Posso M, Louro J, Castells X, Sala M. A systematic review of personalized breast cancer screening strategies. International Cancer Screening Conference. Rotterdam, The Netherlands, 3-5 June 2019. • Louro J, Castells X, Quintana MJ, Posso M, Sala M, Román M. An individualized breast cancer risk prediction model to personalized mammography screeningInternational Cancer Screening Conference. Rotterdam, The Netherlands, 3-5 June 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Sala M, Castell X, Posso MC, Roman M, Louro J, Domingo L, et al. with the participation of the Associació AGATA (Catalan Association of Women Affected by Breast Cancer). Report: Evidence on personalising the population-based breast cancer screening. Barcelona: Agència de Qualitat i Avaluació Sanitàries de Catalunya. Departament de Salut. Generalitat de Catalunya; 2019 (Health Technology Assessment Reports). • Andrea Burón, Francesc Macià. Dissemination of the Early Detection of Colon and Rectal Cancer Program by participating in the Bicycle Party. Agència de Salut Pública de Barcelona (ASPB), 24 March 2019. • Dissemination of the Early Detection of Colon and Rectal Cancer Program by participating in the Urban Walk. Ajuntament de Barcelona and Associació d’Entitats Excursionistes del Barcelonès. Barcelona, 12 May 2019. • Dissemination of the Early Detection of Colon and Rectal Cancer Program by participating in the La Mina Entity Fair. CAP La Mina. Barcelona, 29 May 2019.

112 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Girona Heart Registry

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Jaume Marrugat de la Iglesia Irene Román Dégano (Researcher) [email protected] Silvia Pérez Fernández (Technician) Pau Raduà Roy (Technician) Sussanna Tello Rovira (Technician) Joan Salvador Vila Domènech (Technician) Sandra Farré Anton (Research Assistant) Yolanda Ferrer Campo (Research Assistant) Sonia Gaixas Vasallo (Research Assistant)

The mission of the Girona Heart Registry Research Group is to increase our knowledge of the magnitude of the populational problem of cardiovascular diseases, their molecular, cellular, and environmental mechanisms, and to design the best strategies for preventing them. The ultimate goal for this knowledge is to significantly reduce this disease’s burden on society, creating tools (such as cardiovascular risk funcions) that allow us to transfer the knowledge we acquire to clinical practice. The REGICOR Group also has the mission of training new researchers in this area of knowledge, and has been accredited with the Recognition for Advanced Research by the Catalan Government every two years since 1996. The REGICOR project is well known for having recruited some 11,000 participants

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 113 Epidemiology and Public Health Girona Heart Registry

in population surveys and over 3,000 consecutive acute myocardial infarction (AMI) patients and for having compiled a biobank of DNA and plasma samples between 1995 and 2005 in Girona. The first-ever description of AMI incidence among the population in Spain was published by the REGICOR team. The cardiovascular research project of the REGICOR has yielded over 500 international scientific publications. The REGICOR team has extensive experience in leading collaborative research at the international level. REGICOR promotes a multidisciplinary approach to research from different perspectives (biochemical, molecular, epidemiological, clinical, and genetic) that enriches the study of multifactorial processes such as cardiovascular disease. The group’s research lines focus on descriptive and clinical epidemiology with follow-up of the incidence of AMI and classic risk factors. They have analysed prognostic factors and the incidence of AMI, including biochemical and epigenetic markers, as well as cardiovascular risk, with the development and improvement of cardiovascular risk functions adapted to our environment.

Main Publications

• Hernáez Á, Zomeño MD, Dégano IR, Pérez-Fernández S, Goday A, Vila JS, Civeira F, Moure R, Marrugat J. Exceso de peso en España: situación actual, proyecciones para 2030 y sobrecoste directo estimado para el Sistema Nacional de Salud. Rev Esp Cardiol 2019; 72(11): 916-924. IF 5.126. Q1. • Subirana I, Fernández-Avilés F, Elosua R, Lidón RM, García-Dorado D, Marrugat J, investigadores del estudio ATHOS. Variabilidad interhospitalaria del tratamiento del síndrome coronario agudo en el estudio ATHOS. Rev Esp Cardiol 2019; 72(8): 691- 693. IF 5.126. Q1. • Sayols-Baixeras S, Fernández-Sanlés A, Prats A, Subirana I, Plusquin M, Künzli N, Marrugat J, Basagaña X, Elosua R. Association between long-term air pollution exposure and DNA methylation: The REGICOR study. Environ Res 2019; 176: 108550. IF 5.026. Q1. • De Gonzalo D, Elosua R, Vea A, Subirana I, Sayols-Baixeras S, Marrugat J, Llorente- Cortés V. Soluble low-density lipoprotein receptor-related protein 1 as a biomarker of coronary risk: Predictive capacity and association with clinical events. Atherosclerosis 2019; 287: 93-99. IF 4.255. Q2. • García-Gil M, Comas-Cufí M, Ramos R, Martí R, Alves-Cabratosa L, Parramon D, Prieto-Alhambra D, Baena-Díez JM, Salvador-González B, Elosua R, Dégano IR, Marrugat J, Grau M. Effectiveness of Statins as Primary Prevention in People With Gout: A Population-Based Cohort Study. J Cardiovasc Pharmacol Ther 2019; 24(6): 542-550. IF 2.57. Q2. See all Publications

114 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Girona Heart Registry

Ongoing Research Projects

• Role of micro RNAs expressed by human endothelial and vascular smooth muscle cells in myocardial infarction. (MIRMID: micro RNAs in Myocardial Infarction Disease) - Financing institution: Fundación BBVA (PR-16_BIO_CAR_0041) - Period: from 2016 to 2019 - Principal investigator: Marrugat de la Iglesia, Jaume • Validation of a coronary heart disease risk calculator adapted to Human Immunodeficiency Virus infected patients. The COMVIH-COR project - Financing institution: Gilead Sciences S.L.U (GLD17-00224) - Period: from 2018 to 2020 - Principal investigator: Marrugat de la Iglesia, Jaume • Optimization and assessment of high-, intermediate- and low-risk cut-points of cardiovascular risk functions used in primary prevention - Financing institution: Instituto de Salud Carlos III (PI18/00030) - Period: from 2019 to 2021 - Principal investigator: Marrugat de la Iglesia, Jaume • PrevCardio: Desarrollo de una herramienta para la prevención personalizada de la enfermedad cardiovascular en población general - Financing institution: Sociedad Española de Cardiología - Period: from 2019 to 2020 - Principal investigator: Marrugat de la Iglesia, Jaume See all Projects

Participation in Research Networks

• CIBER Enfermedades Cardiovasculares - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB16/11/00229) - Period: from 2003 - Principal investigator: Marrugat de la Iglesia, Jaume

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 115 Epidemiology and Public Health Girona Heart Registry

Clinical Trials Signed in 2019

• Preparation and implementation of the study protocol “Ensayo clínico abierto, no aleatorizado en dos conglomerados constituidos por dos poblaciones urbanas distintas, comparativo de una intervención preventiva con un grupo control sin intervención sobre el control de factores de riesgo cardiovascular. Healthy Communities”. - Sponsor: Fundació Privada SHE - Budget: 62,600 € - Principal investigator: Marrugat de la Iglesia, Jaume • A standardized comparison of cardiovascular risk factor prevalence between HIV- infected patients and general population & cost-effectiveness of treating dyslipemia in high cardiovascular risk patients - Protocol: IN-ES-985-5373 - Sponsor: Gilead Sciences, S.L.U. - Budget: 72,360 € - Principal investigator: Marrugat de la Iglesia, Jaume

Awards

• Marrugat de la Iglesia, Jaume; Román Dégano, Irene. 2019 Second prize for the most- cited article, long-term in Revista Española de Cardiología Journal. Sociedad Española de Cardiología (SEC). 18/10/2019. • Marrugat de la Iglesia, Jaume; Román Dégano, Irene. Prize for the best Primary Care article. Col·legi Oficial de Metges de Barcelona. 27/11/2019.

Appointments

• Jaume Marrugat. Member of Scientific Committee. CODI IAM. Departament de Salut de la Generalitat de Catalunya. 2018 to date. • Jaume Marrugat. Member of Scientific Committee. Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQUAS). 2018 to date.

116 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Girona Heart Registry

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Gaixas Sònia, Román Dégano Irene, Pérez-Fernández Sílvia. Workshop Mesure your cardiovascular health. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019. • Irene Román, Susanna Tello. Excursion through the different stages of a research project. High school students form the Institut Secretari Coloma. Escolab Project. Barcelona Science Programme of the Institute of Culture. 21 March 2019. • Jaume Marrugat. Conference on risk and fears. Biblioteca Can Fabra, Barcelona, 14 February 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 117 Health Services

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Jordi Alonso Caballero María Jesús Blasco Cubedo (Researcher) [email protected] Olatz Garin Boronat (Researcher) Montserrat Ferrer Forés (Researcher) Antón López Alfonso (Researcher) Philippe Mortier (Researcher) Yolanda Pardo Cladellas (Researcher) Gemma Vilagut Saiz (Researcher) Laura Ballester Coma (PhD Student) Ana de Inés Trujillo (PhD Student) Karina Mayoral Ortiz (PhD Student) Beatriz Puértolas Gracia (PhD Student) Itxaso Alayo Bueno (Technician) Javier Gómez Sánchez (Technician) Àngels Pont Acuña (Technician) Purificación Barbas López (Research Assistant) Carme Gasull Planes (Research Assistant) Luisa Aurea Martín Morris (Research Assistant)

Our research focuses on methods for measuring perceived health, patient-reported outcomes (PROs), disability and the burden of disease. Our main areas of research apply these methods to assessing the burden of common mental health disorders and to evaluating the comparative effectiveness of interventions for chronic diseases, especially in cancer and asthma. Our research is carried out in collaboration with several

118 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Health Services

international research networks, including the World Mental Health (WMH) Surveys Consortium, and TrueNTH Global Registry – Prostate Cancer Outcomes, a Movember Foundation international initiative. Knowledge transfer is also an important focus for the group, which plays a leading role in BiblioPRO, the online library of PROs in Spanish containing more than 2300 instruments, which is now going to cover all languages with the new website BiblioPRO International. We have developed a tool to evaluate the quality of these instruments (EMPRO) and a “Procedure and system to evaluate the quality of life related to the health of an individual” (patent n P200600211, May 1999). In addition, we collaborate as partners in international research initiatives and projects, such as SISAQOL, PROMIS- Health Organization, ICHOM, OECD-PaRIS, IQOD, MHADIE, KIDSCREEN, ASTRO- LAB, or EuroQol. We are engaged in a number of educational and mentoring activities, including the Master’s programme in Public Health, the degree in Medicine, and other official education from both Pompeu Fabra University (UPF) and the Autonomous University of Barcelona (UAB), as well as the PSMAR Teaching Unit of Specialists in Preventive Medicine and Public Health. Our team comprises some 15 professionals with different backgrounds, such as life sciences, psychology, statistics, and others; it is part of the CIBER de Epidemiología y Salud Pública (CIBERESP) of the Instituto de Salud Carlos III, and is recognized as a consolidated research group by the Generalitat de Catalunya.

Main Publications

• Soto-Sanz V, Castellví P, Piqueras JA, et al. Internalizing and externalizing symptoms and suicidal behavior in young people: a systematic review and meta-analysis of longitudinal studies. Acta Psychiatr Scand 2019; 140(1): 5-19. IF 4.984. Q1. • Hernández G, Garin O, Dima AL, et al. EuroQol (EQ-5D-5L) Validity in Assessing the Quality of Life in Adults With Asthma: Cross-Sectional Study. J Med Internet Res 2019; 21(1): e10178 IF 4.945. D1. • Mayoral K, Rajmil L, Murillo M, et al. Measurement Properties of the Online EuroQol- 5D-Youth Instrument in Children and Adolescents with Type 1 Diabetes Mellitus: Questionnaire Study. J Med Internet Res 2019; 21(11): e14947. IF 4.945. D1. • Miranda-Mendizábal A, Castellví P, Alayo I, et al. Gender commonalities and differences in risk and protective factors of suicidal thoughts and behaviors: A cross- sectional study of Spanish university students. Depress Anxiety 2019; 36(11): 1102- 1114. IF 4.935. D1. • Blasco-Cubedo MJ, Vilagut G, Almenara J, et al. Suicidal Thoughts and Behaviors: Prevalence and Association with Distal and Proximal Factors in Spanish University Students. Suicide Life Threat Behav 2019; 49(3): 881-898. IF 3.032. Q1. See all Publications

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 119 Epidemiology and Public Health Health Services

Ongoing Research Projects

• Efectividad del tratamiento de las lesiones masivas del manguito rotador del hombro evaluada con resultados relevantes para el paciente: estudio con metodología mixta - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00152) - Period: from 2019 to 2021 - Principal investigators: Ferrer Forés, Montserrat; Torrens Cánovas, Carles • Incidencia poblacional de la tentativa y de la repetición de tentativa de suicidio: evaluación del Código riesgo suicidio de Cataluña - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00521) - Period: from 2018 to 2020 - Principal investigator: Alonso Caballero, Jordi • TrueNTH Global Registry – Prostate Cancer Outcomes - Financing institution: Movember Europe. PCO-CRV - Period: from 2017 to 2020 - Principal investigator: Ferrer Forés, Montserrat • Aplicación de los instrumentos PRO en España: revisión sistemática y recomendaciones basadas en la evidencia - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00130) - Period: from 2017 to 2019 - Principal investigator: Garin Boronat, Olatz • Evaluación del tratamiento con broncodilatadores de acción larga en los niños con asma: estudio observacional prospectivo - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00449) - Period: from 2016 to 2020 - Principal investigator: Ferrer Forés, Montserrat See all Projects

Participation in Research Networks

• CIBERESP: Epidemiología y salud pública - Financing institution: Fondo de Investigación Sanitaria. ISCIII. (CB06/02/0046) - Period: from 2006 - Principal investigator: Alonso Caballero, Jordi; co-PI: Ferrer Forés, Montserrat • MOVEMBER: TrueNTH Global Registry – Prostate Cancer Outcomes - Financing institution: Movember Foundation - Period: from 2016 - Principal investigator: Ferrer Forés, Montserrat

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• PROMIS: Patient-Reported Outcomes Measurement Information System - Financing institution: PROMIS Health Organization (PHO) - Period: from 2015 - Principal investigator: Alonso Caballero, Jordi • World Mental Health (WMH) Survey Consortium - Financing institution: World Health Organization (WHO) - Period: from 2007 - Principal investigator: Alonso Caballero, Jordi; Vilagut Saiz, Gemma

Theses

• Blasco-Cubedo MJ. Pensamientos y conductas suicidas en universitarios españoles: Frecuencia, factores de riesgo y de protección. Universitat Pompeu Fabra - Director: Alonso Caballero, Jordi - Date of defense: 22/02/2019 • Zaror C. Calidad de vida relacionada con la salud oral en niños y adolescentes. Universitat Autònoma de Barcelona - Director: Ferrer Forés, Montserrat; Martínez-Zapata, MJ - Date of defense: 26/07/2019

Awards

• Jordi Alonso. Presidential Award 2019. International Society for Quality of Life Research (ISOQOL). 23/10/2019 • Jordi Alonso. Highly Cited Researcher in the World in the field of Psychiatry/Psycology (2019, 2018, 2017 and 2016). Clarivate Analytics, Thomson Reuters. November 2019

Appointments

• Jordi Alonso. Deputy Scientific Director-Steering Committee of CIBERESP. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP). 28/11/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 121 Epidemiology and Public Health Health Services

Outreach

Conferences, Seminars and Courses

• Jordi Alonso Caballero, Montserrat Ferrer Forés (organizers); Yolanda Pardo, Itxaso Alayo, Olatz Garin, Karina Mayoral, Àngels Pont, Gemma Vilagut, Víctor Zamora (participating researchers). IV BiblioPRO Scientific Conference: The role of PROs in the evaluation of health service providers. Instituto de Salud Carlos III (ISCIII). Madrid, 21 February 2019. • Montse Ferrer. PROs, PREs y valor (communication); Métrica de los PROs (workshop). VIII Congreso de Gestión Clínica: ¿Motor de la Innovación Organizativa? Fundación Gaspar Casal. Las Palmas de Gran Canaria, 20-21 May 2019 • Jordi Alonso. Workshop: Advances in Patient-Reported Outcomes, Postgraduate Diploma in Health Technology Assessment to Oncologists. Sociedad Española de Oncología Médica (SEOM) and Fundación Gaspar Casal, with the collaboration of Barcelona School of Management (BSM)-UPF and Centre de Recerca en Economia i Salut (CRES). Madrid. 13 September 2019 • Jordi Alonso. Responsible research and impact to society (opening speech). VII Conference REDISSEC: Towards research with an impact on society. Agència de Qualitat i Avaluació Sanitàries de Catalunya (AquAS). Universitat Pompeu Fabra (UPF), Barcelona, 7 November 2019. • Jordi Alonso (guest speaker). Instrumentos de resultados en salud. II Encuentro de Expertos en Gestión Sanitaria y Economía de la Salud. Barcelona, 29 November 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Jordi Alonso. Participating researcher. Elaboration of a protocol for the evaluation of the effectiveness of approching programmes to witnesses of domestic violence in the field of health in Catalonia (Code: 3020190324). Health Evaluation and Quality Agency of Catalonia (AQuAS). Barcelona, 2019.

122 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Research Group in Nursing Care

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Silvia Esteban Sepúlveda Laia Lacueva Pérez (Researcher) [email protected] Elisabeth Lafuente Cabrero (Researcher) María Isabel Márquez Romero (Researcher) Guillermo Pedreira Robles (Researcher) Maria Isabel Flores Muxi (Technician) Judit Llopis Serra (Technician) Núria Orfila Tena (Technician) Rosa Villanueva Boloix (Technician)

The Research Group in Nursing Care arises from the need to formally integrate the Parc de Salut Mar nursing into the research field, encompassing all the parts of which it is comprised (Hospital del Mar, Hospital de l’Esperança, Centre Peracamps, Centre Fòrum, Centre Emili Mira and Escola Superior d’Infermeria del Mar). The Group’s objective is to generate scientific nursing knowledge and to apply it to evidence-based assistance, with the ultimate aim of improving health, both in terms of care given to the patient and to the community. It is worth noting that several members of the group have participated or are actively involved in various national and international research projects. The main lines of research will focus on training patients to manage their own health and the training of nurses who care for patients.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 123 Epidemiology and Public Health Research Group in Nursing Care

Main Publications

• Roviralta M, Moreno-Poyato AR, Rodríguez-Nogueira Ó, Duran X, Roldán-Merino JF, MiRTCIME.CAT Working Group. Relationship between the nursing practice environment and the therapeutic relationship in acute mental health units: A cross- sectional study. Int J Ment Health Nurs 2019; 28(6): 1338-1346. IF 2.433. D1. • Esteban S, Moreno-Casbas MT, Fuentelsaz-Gallego C, Ruzafa-Martínez M. The nurse work environment in Spanish nurses following an economic recession: from 2009 to 2014. J Nurs Manag 2019; 27(6): 1294-1303. IF 2.386. D1. • Moreno-Poyato AR, Delgado-Hito P, Leyva-Moral JM, Casanova-Garrigós G, Montesó-Curto P. Implementing Evidence-Based Practices on the Therapeutic Relationship in Inpatient Psychiatric Care: a Participatory Action Research. J Clin Nurs 2019; 28(9-10): 1614-1622. IF 1.757. Q1. • Pedreira-Robles G, Aguayo-González MP. From physical to emotional pain in chronic kidney disease: Nurses’ perceptions. J Ren Care 2019; 45(4): 212-222. IF 1.216. Q3. See all Publications

Ongoing Research Projects

• Impacte de la implantació de Guías de Buena Práctica en les creències-actituds i conducta davant la pràctica basada en l’evidència i en la percepció de l’entorn laboral de les infermeres - Financing institution: Col·legi Oficial d’Infermeria de Barcelona (PR-259/2018) - Period: from 2019 to 2021 - Principal investigator: Esteban Sepúlveda, Silvia See all Projects

124 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Social Epidemiology and Occupational Health

> Epidemiology and Public Health RESEARCH GROUP

Group Leader Members Consol Serra Pujadas Julià del Prado Vinuesa (Researccher) [email protected] Jordi Delclòs Clanchet (Researcher) Fernando García Benavides (Researcher) David Gimeno Ruiz de Porras (Researcher) Cristina Portellano Ortiz (Researcher) José María Ramada Rodilla (Researcher) Mireia Utzet Sadurní (Researcher) Rocío Villar Vinuesa (Researacher) Amaia Ayala García (PhD Student) Julio César Hernando Rodríguez (PhD Student) Michael Silva Peñaherrera (PhD Student) Mercè Soler Font (PhD Student) Montserrat Fernàndez Busquets (Research Assistant)

The Research Group in Social Epidemiology and Occupational Health (CISAL) is an IMIM research group led by Dr. Consol Serra Pujadas. CISAL is also part of the Department of Experimental and Health Sciences at Pompeu Fabra University and is recognized by the CIBER of Epidemiology and Public Health (since 2008) as a consolidated group by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (since 2002). The European strategy on Safety and Health at Work draws attention to the need to keep people in the labor market, through healthy work environments, effective return

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 125 Epidemiology and Public Health Social Epidemiology and Occupational Health

programs for those who leave the labor market, whether temporarily or permanently, for health reasons, and with a focus on the employment of vulnerable groups, such as migrants, ethnic minorities, women and workers in precarious employment. CISAL investigates occupational health issues with major implications for workers, companies and governments that are particularly sensitive for social welfare systems, with the objective of contributing to the improvement of workers’ health, evaluating the impact of preventive programs in the workplace and informing the priorities of health policies. CISAL research and transfer focuses on a variety of current work-related health problems that include (but are not limited to) musculoskeletal disorders, work injuries, workplace prevention programs and the determinants of absence due to illness and temporary/permanent disability. Its research also emphasizes groups of vulnerable workers, with a focus on the aging population, women, migrants and precarious employment. CISAL is involved in the development of new measurement tools for the Spanish working population and surveys of working conditions and health. It is also involved in ongoing research collaboration with universities and institutions in Europe, North America and Latin America.

Main Publications

• Villar R, Serra L, Serra C, Benavides FG. Working conditions and absence from work during pregnancy in a cohort of healthcare workers. Occup Environ Med 2019; 76(4): 236-242. IF 3.556. Q1. • Soler-Font M, Ramada JM, van Zon SKR, Almansa J, Bültmann U, Serra C, INTEVAL_ Spain research team. Multifaceted intervention for the prevention and management of musculoskeletal pain in nursing staff: Results of a cluster randomized controlled trial. PLoS ONE 2019; 14(11): e0225198. IF 2.776. Q2. • Serra C, Soler-Font M, García AM, Peña P, Vargas-Prada S, Ramada JM. Prevention and management of musculoskeletal pain in nursing staff by a multifaceted intervention in the workplace: design of a cluster randomized controlled trial with effectiveness, process and economic evaluation (INTEVAL_Spain). BMc Public Health 2019; 19: 348. IF 2.567. Q2. • Coggon D, Ntani G, Walker-Bone K, Felli VE, Harari F, Barrero LH, Felknor SA, Rojas M, Cattrell A, Serra C, Borchini R, Solidaki E, Merisalu E, Habib RR, Sadeghian F, Kadir MM, Peiris-John RJ, Matsudaira K, Nyantumbu-Mkhize B, Kelsall HL, Harcombe H. Determinants of international variation in the prevalence of disabling wrist and hand pain. BMC Musculoskelet Disord 2019; 20: 436. IF 2.002. Q2. • Benavides FG, Ramada JM, Ubalde-López M, Delclòs GL, Serra C. A hospital occupational diseases unit: an experience to increase the recognition of occupational disease. Med Lav 2019; 110(4): 278-284. IF 0.58. Q4. See all Publications

126 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Epidemiology and Public Health Social Epidemiology and Occupational Health

Ongoing Research Projects

• INTEVAL-Plus Project: Cluster-randomized controlled trial of a multicomponent workplace intervention to improve musculoskeletal health in hospital workers - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00779) - Period: from 2018 to 2020 - Principal investigator: Ramada Rodilla, José María • CEPS Project: Burden of Occupational Diseases treated at the Spanish National Health System - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00061) - Period: from 2017 to 2019 - Principal investigator: Serra Pujadas, Consol See all Projects

Participation in Research Networks

• CIBER Epidemiology and Public Health - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB06/02/1003) - Period: from 2008 to 2019 - Principal investigator: García Benavides, Fernando • Expert Network on Working and Employment Conditions Surveys (ECoTES NETWORK) - Financing institution: Superintendencia de Riesgos del Trabajo de Argentina, Universidad Nacional de Costa Rica, Universidad Internacional SEK Ecuador, University of Texas USA, Universidad de la República de Uruguay, CISAL- Universitat Pompeu Fabra - Period: from 2014 to 2020 - Principal investigator: García Benavides, Fernando

Theses

• Villar R. Maternidad y trabajo remunerado. Utilización de las prestaciones sociales durante el embarazo en una muestra de trabajadoras embarazadas de un hospital de Barcelona (España). Universitat Pompeu Fabra - Director: Serra Pujadas, Consol; García Benavides, Fernando - Date of defense: 20/02/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 127 Epidemiology and Public Health Social Epidemiology and Occupational Health

Awards

• Julio C. Hernando Rodríguez, predoctoral researcher at CISAL-UPF. Best communication presented by young research staff. XXXVII Annual Scientific Meeting of the SEE. 3-6/9/2019. • Martínez-Solanas È, López-Ruiz M, Wellenius GA, Gasparrini A, Sunyer J, Benavides FG, Basagaña X. Evaluation of the Impact of Ambient Temperatures on Occupational Injuries in Spain. Environ Health Perspect 2018; 126(6): 067002. Best original Epidemiology Article of 2018. Spanish Society of Epidemiology 16/10/2019.

Outreach

Conferences, Seminars and Courses

• Consol Serra. Nuevas estrategias para identificar y reconocer las enfermedades profesionales. Jornadas sobre Manejo Integral de Enfermedades Profesionales: Guías de Actuación y Diagnóstico de Enfermedades Profesionales. Coordinación de Estudios e Investigación de Salud en el Trabajo (CEISAT-SRT). Buenos Aires (Argentina), 3 and 24 July 2019. • Consol Serra, Jordi Delclòs. Conferences: Actualitat de l’especialitat: mirant el futur; Un canvi paradigmàtic en l’enfocament de la salut laboral: el benestar total del treballador. Recordem al Dr. Francesc Arró i Triay: passat, present i futur de la Medicina del Treball. Col·legi Oficial de Metges de Barcelona. Barcelona, 23 May 2019. • Fernando G. Benavides. Treball segur i saludable. Jornada “El Futur del Treball”. Departament de Salut, Generalitat de Catalunya. Barcelona, 12 April 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Fernando G. Benavides. Las enfermedades profesionales, estado actual y propuestas de mejora. Jornada “Las Enfermedades Profesionales en el punto de mira”. UGT Catalunya. Barcelona, 25 April 2019. • Fernando G. Benavides. Salud y Trabajo: desde la Revolución Industrial a la Revolución Digital. Fundación La Maquinista (MACOSA). Barcelona, 11 December 2019.

128 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Healthy Cities and Environmental Justice

> Epidemiology and Public Health ASSOCIATED GROUP

Group Leader Members Isabelle Anguelovski Francesc Baró Porras (Researcher) [email protected] Helen Cole (Researcher) James Connolly (Researcher) Melissa García Williams (Researcher) Santiago Gorostiza Langa (Researcher) Panagiota Kotsila (Researcher) Johannes Langemeyer (Researcher) Filkatsvetkova Sekulova (Researcher) Margarita Triguero Mas (Researcher) Carmen Pérez del Pulgar Frowein (PhD Student) Galia Shokry (PhD Student) Laura Jiménez Fernández (Research Assistant)

The group’s research line focuses on the interplay between social and environmental determinants of healthy and fair cities and on the impacts of greener, more sustainable, more resilient cities. Many of our studies examine environmental and health inequities resulting from urban planning decisions and interventions, and the community actions, policies, and planning decisions arising to address such inequities. We also evaluate how cities incorporate health risks, impacts, and emergencies into urban planning and policy, as well as the opportunities for and constraints faced by

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 129 Epidemiology and Public Health Healthy Cities and Environmental Justice

cities in bringing health, health equity, and health services to the centre of policy agendas, planning decisions, and implementation. Finally, the group examines the effects on physical and mental health and well-being of exposure to urban gentrification and displacement. In addition, we analyse how the protective effects of various neighbourhood amenities, such as healthcare and health services, green space, and others, may be modified by gentrification. Particular attention is paid here to the role played by gentrification as a moderating factor between exposure to new green and sustainable urban environments and health outcomes. Our specific studies examine: • Patterns and causes of health inequities embedded in urban development processes. • Advancing public health theory on complex urban exposures, such as gentrification and related urban processes. • Developing new measurement methods of objective and perceived gentrification for public health research. • Examining the pathways and mechanisms between gentrification, displacement, and health. • Evaluating the complex relationships between urban patterns of gentrification and access to and delivery of health care. • Studying the impacts of urban greenspace access on health, with special emphasis on health (in)equity. • Health and wellbeing effects of green rooftops for people with disabilities: effects and potential mechanisms.

Main Publications with IMIM

• Anguelovski I, Connolly JJT, Pearsall H, Shokry G, Checker M, Maantay J, Gould K, Lewis T, Maroko A, Roberts JT. Why green “climate gentrification” threatens poor and vulnerable populations. Proc Natl Acad Sci U S A 2019; 116(52): 26139-26143. IF 9.528. Q1. • Cole HVS, Triguero-Mas M, Connolly J, Anguelovski I. Determining the Health Benefits of Green Space: Does gentrification matter? Health and Place 2019; 57: 1-11. IF 3.202. Q1.

MORE INFO

130 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY

Programmes

Inflammatory and Cardiovascular Disorders

15 185 57 318 Research Professionals Research Publications groups projects

Programme Director Francesc Xavier Nogués Solan

RESEARCH GROUPS Kidney Disease Julio Pascual B Cell Biology Andrea Cerutti Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Biomedical Research in Heart Diseases Esther Barreiro Núria Farré Musculoskeletal Research Cell Research on Inflammation and Cartilage Francesc Xavier Nogués Jordi Monfort Myogenesis, Inflammation & Muscle Function Critical Illness Joaquim Gea Joan Ramon Masclans Neuroimmunology Hepatologic Research Jose Enrique Martínez Montserrat García Neurovascular Immunity and Infection Jaume Roquer José Miguel López-Botet Rehabilitation Infectious Pathology and Antimicrobials Esther Duarte Juan Pablo Horcajada

Inflammatory and Neoplastic Dermatological Diseases Ramon Maria Pujol

132 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Programme

The Research in Inflammatory and Cardiovascular Disorders (RICAD) programme currently gathers fifteen groups, mostly led by researchers from Parc de Salut MAR with clinical duties, including two with recognized expertise in Immunology. Scientific interests are oriented to the study of a variety of disorders involving inflammatory processes in their pathophysiology. On the other hand, knowledge on the molecular basis of inflammation is promoting the development of novel therapeutic approaches with an impact in other health problems (e.g. cancer, neurodegenerative disorders), thus fostering internal collaborations between different IMIM programmes. Among such a diversity of research lines, those more competitive and aligned with hospital health care priorities receive a special consideration in the framework of the institutional strategic plan. Internal seminars aimed to promote communication between the different groups are organized monthly. Established researchers have specific space assigned at IMIM premises, facilitating their interaction with other institutions located at the Barcelona Biomedical Research Park (PRBB), as well as access to shared infrastructures and core facilities. Currently, laboratory space constraints become a limitation for integrating new researchers and the development of emerging groups. Overall, RICAD satisfactorily contributed to IMIM achievements according to the rate/visibility of indexed publications, competitive fund raising and reinvestment of clinical trials income to support academic research. Most RICAD groups participate in national research ISCIII networks (RETICs, CIBERs), training PhD students and medical residents. An increase of productive collaborations, both internal and across other IMIM programmes (i.e. Cancer), is reflected by co-authored publications. An effort to further enhance leadership/visibility in publications, internationalization and transfer activities is warranted.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 133 B Cell Biology

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Andrea Cerutti Giuliana Magri (Researcher) (ICREA Professor) Roser Tachó Piñot (Technician) [email protected] Sonia Tejedor Vaquero (Technician)

Members of the B Cell Biology research group use different cellular, histological, and molecular techniques to address basic questions related to B cell activation and antibody production. B cells are a lymphocyte subset that repels foreign pathogens and controls endogenous commensal microbes by producing antibodies, also termed immunoglobulins (Igs). We are especially interested in a process called Ig heavy chain class switching. By replacing IgM with IgD, IgG, IgA or IgE, class switching provides antibodies with novel effector functions without changing their antigen specificity. In general, our goal is to dissect the mechanisms by which different subsets of systemic and mucosal B cells regulate class switching and antibody production during humoral responses to commensal or pathogenic microbes. We are also interested in the clonal architecture of these B cell responses.

134 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders B Cell Biology

Main Publications

• Galindo-Campos MA, Bedora-Faure M, Farrés J, Lescale C, Moreno-Lama L, Martínez C, Martín-Caballero J, Ampurdanés C, Aparicio P, Dantzer F, Cerutti A, Deriano L, Yélamos J. 2019, Coordinated signals from the DNA repair enzymes PARP-1 and PARP-2 promote B-cell development and function. Cell Death and Differ 2019 Dec; 26 (12): 2667-2268. IF 8.086. D1. See all Publications

Ongoing Research Projects

• Gut plasma cell responses in health and IBD (Retos grant) - Financing institution: Ministerio de Educación y Ciencia (RTI2018-093894-B-I00) - Period: from 2018 to 2021 - Principal investigator: Cerutti, Andrea • Humoral responses in the respiratory mucosa: role of IgD - Financing institution: Ministerio de Educación y Ciencia (SAF2014-52483R) - Period: from 2015 to 2019 - Principal investigator: Cerutti, Andrea See all Projects

Appointments

• Andrea Cerutti. Member of the ERC Consolidator Grant Evaluation 2019, Panel LS6. European Research Council. 14-16/05/19 (Step 1). • Andrea Cerutti. Member of the ERC Consolidator Grant Evaluation 2019, Panel LS6. European Research Council. 08-10/10/19 (Step 2).

Outreach

Conferences, Seminars and Courses

• Andrea Cerutti. Invited speaker. Marginal Zone Lymphoma Scientific Workshop. New York (NY), 17-18 April 2019. • Andrea Cerutti. Invited speaker. Immunology Seminar Series at the Kennedy Institute of Oxford University. Oxford (UK), 24 February 2019. • Giuliana Magri. Invited speaker. Immunology Seminar Series. Manchester (UK), 28 February 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 135 Biomedical Research in Heart Diseases

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Núria Farré López Laia Carla Belarte Tornero (Researcher) [email protected] Mercè Cladellas Capdevila (Researcher) Paloma Garcimartín Cerezo (Researcher) Julio Martí Almor (Researcher) Aleksandra Mas-Stachurska (Researcher) Lluís Molina Ferragut (Researcher) Marta Tajes Orduña (Researcher) Helena Tizón Marcos (Researcher) Ermengol Vallès Gras (Researcher) Beatriz Vaquerizo Montilla (Researcher) Consol Ivern Díaz (Technician) Alejandro Negrete (Technician) Laia Yáñez Bisbe (Technician) Marta Gimeno López (Research Assistant)

The Group of Biomedical Research in Heart Diseases (GREC) focuses on generating new translational research in the field of Cardiovascular Diseases, where bedside unresolved questions generate hypotheses for applied basic and clinical research with potential impact on patient management. The group works in four main areas of cardiology (coronary heart disease, valvular heart disease, arrhythmias, and cardiomyopathies/heart failure), around which it has established three main research areas: 1) identification of biomarkers of cardiovascular diseases; 2) study of the effect of ageing in heart diseases; and 3) application of new technologies in the daily management of cardiac patients.

136 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Biomedical Research in Heart Diseases

Main Publications

• Rodríguez-Costoya I, Tizon H, Vaquerizo B, Salvatella N, Martí-Almor J, Millán R. Coronary Lithoplasty: Initial Experience in Coronary Calcified Lesions. Rev Esp Cardiol 2019; 72(9): 788-790. FI 5.126. Q1. • Ruiz-Bustillo S, Ivern C, Badosa N, Farré N, Marco E, Bruguera J, Cladellas M, Enjuanes C, Cainzos-Achirica M, Martí-Almor J, Comín-Colet J. Efficacy of a nurse-led lipid-lowering secondary prevention intervention in patients hospitalized for ischemic heart disease: A pilot randomized controlled trial. Eur J Cardiovasc Nurs 2019; 18(5): 366-374. FI 2.497. Q1. • Vallès E, Benito B, Jiménez J, Cabrera S, Alcalde O, Altaba C, Guijo MA, Fan R, Martí- Almor J. Double factor single shot to diminish complications in cryoballoon ablation procedures for atrial fibrillation. J Interv Card Electrophysiol 2019; 55(1): 17-26. FI 1.534. Q4. • Garcimartín P, Pardo Y, Verdú JM, Delgado-Hito P, Astals M, Comín J. Transcultural adaptation into Spanish of the Patient empowerment in long-term conditions questionnaire. Aten Primaria 2019; 51(1): 24-31. FI 1.346. Q3. • Ribas N, Recasens L, Pérez-Fernández S, Bazan V, Pedro-Botet J, Ruiz-Bustillo S, Elosua R, Martí-Almor J. A new rational approach to reach LDL-cholesterol concentration objectives after an acute coronary syndrome. Clin Investig Arterioscler 2019; 31(3): 93-100. See all Publications

Ongoing Research Projects

• Diagnóstico y tratamiento precoz de cardiotoxicidad en pacientes onco-hematológicos en el marco de una unidad multidisciplinar - Financing institution: Sociedad Española de Cardiología - Period: from 2018 to 2019 - Principal investigator: Belarte Tornero, Laia Carla • Ensayo clínico randomizado: valoración de la intervención multidisciplinar conjunta de cardiólogo y geriatra en pacientes ancianos tras ingreso reciente por insuficiencia cardiaca - Financiang institution: Beca Primitivo de la Vega. Fundación MAPFRE - Period: from 2017 to 2020 - Principal investigator: Farré López, Núria See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 137 Inflammatory and Cardiovascular Disorders Biomedical Research in Heart Diseases

Participation in Research Networks

• CIBERCV. Estudio prospectivo multidisciplinar de nuevos indicadores fenotípicos y pronósticos en pacientes con insuficiencia cardiaca de debut (REDINSCOR III) - Financing institution: Fondo de Investigación Sanitaria. ISCIII - Period: from 2017 to 2020 - Principal investigator: Solé González, Eduard

Clinical Trials Signed in 2019

• A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel- group Study to Investigate the Efficacy and Safety of CSL112 in Subjects with Acute Coronary Syndrome - Protocol: CSL112_3001 - Sponsor: CSL Behring LLC - Budget: 82,336 € - Principal investigator: Recasens Gracia, Lluís • Estudio doble ciego, aleatorizado, controlado con placebo, con grupos paralelos de AP30663 administrado por vía intravenosa para cardioversión en pacientes con fibrilación auricular - Protocol: AP30663 - 2001 - Sponsor: Acesion Pharma APS - Budget: 20,915.84 € - Principal investigator: Martí Almor, Julio • Investigación clínica del sistema de estimulación ENO/TEO/OTO en entornos de IRM (CAPRI) - Protocol: IBSY06 - Sponsor: Sorin CRM SAS - Budget: 18,225 € - Principal investigator: Martí Almor, Julio

Outreach

Conferences, Seminars and Courses

• Núria Farré López. III Jornada d’Actualització en la IC. IMIM, Barcelona, 19 November 2019.

138 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Cell Research on Inflammation and Cartilage

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Jordi Monfort Faure Emma Beltrán Catalán (Researcher) [email protected] Pedro Benito Ruiz (Researcher) Josep Blanch Rubio (Researcher) Manel Ciria Recasens (Researcher) Santos Martínez Díaz (Researcher) Juan Carlos Monllau García (Researcher) Carolina Pérez García (Researcher) Tarek Carlos Salman Monte (Researcher) Laura Tío Barrena (Researcher) Raúl Torres Claramunt (Researcher) Irene Carrión Barberà (Technician) Jone Llorente Onaindia (Technician) Luciano Polino (Technician) Anna Ribes Mas (Technician)

Our group comprises multidisciplinary researchers with skills in orthopedic surgery, rheumatology, psychology and biology, with broad experience in clinical and biomedical research in the field of clinical surgery and degenerative diseases. Our research focuses mainly on three areas: • Study of immune-mediated inflammatory diseases: the studies focus mainly on the search for prognostic markers, improvement of diagnostic imaging techniques to

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 139 Inflammatory and Cardiovascular Disorders Cell Research on Inflammation and Cartilage

allow earlier diagnosis and to increase knowledge of the pathophysiology of lupus, fibromyalgia and osteoporosis. • Knee joint disorders: our group focuses on the study of new approaches in the surgical treatment of knee disorders. The principal areas are biomaterial engineering for partial meniscal and bone replacement, with or without stem cells, and the improvement of surgical approaches to ligament reconstruction, osteotomy and joint prosthesis. • Study of osteoarthritis physiopathology: our group aims to contribute to expanding knowledge of the processes that take place in the development and progress of the disease by studying the cartilage extracellular matrix and its degradation. We are also involved in developing a new classification of the osteoarthritic patient according to phenotype (clinical, physical, behavior and imaging characteristics) to allow for more personalized therapy. Finally, the group is a pioneer in the study of the central sensitization to pain in this type of patient.

Main Publications

• Aterido A, Cañete JD, Tornero J, Ferrándiz C, Pinto JA, Gratacós J, Queiró R, Montilla C, Torre-Alonso JC, et al. (Pérez C). Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis. Ann Rheum Dis 2019; 78(3): e214158. IF 14.299. D1. • Atienza-Mateo B, Martín-Varillas JL, Calvo-Río V, Demetrio-Pablo R, Beltrán E, Sánchez-Bursón J, Mesquida M, Adán A, Hernández MV, Hernández-Garfella M, et al. Comparative study of infliximab versus adalimumab in refractory uveitis due to Behçet’s disease, National multicenter study of 177 cases. Arthritis Rheumatol 2019; 71(12): 2081-2089. IF 9.002. D1. • Sanchis-Alfonso V, Ginovart G, Alastruey-López D, Montesinos-Berry E, Monllau JC, Alberich-Bayarri A, Pérez MA. Evaluation of Patellar Contact Pressure Changes after Static versus Dynamic Medial Patellofemoral Ligament Reconstructions Using a Finite Element Model. J Clin Med 2019; 8(12): 2093. IF 5.688. D1. • Torrente V, Salman-Monte TC, Rúa-Figueroa I, de Uña-Álvarez J, Balboa-Barreiro V, López-Longo FJ, Galindo-Izquierdo M, Calvo-Alen J, Olivé-Marqués A, Mouriño- Rodríguez C, et al., RELESSER Study Group of the Spanish Society of Rheumatology (SER) and the Study Group of Systemic Autoimmune Diseases of the SER (EAS- SER). Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Semin Arthritis Rheu 2019; 48(6): 1025- 1029. IF 5.072. Q1. • Pujol J, Ramos-López D, Blanco-Hinojo L, Pujol G, Ortiz H, Martínez-Vilavella G, Blanch J, Monfort J, Deus J. Testing the effects of gentle vibrotactile stimulation on symptom relief in fibromyalgia. Arthritis Res Ther 2019; 21: 148. IF 4.148. Q2. See all Publications

140 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Cell Research on Inflammation and Cartilage

Ongoing Research Projects

• Caracterización clínica, radiológica y analítica del paciente con artrosis de rodilla y necesidad de artroplastia - Financing institution: AEI (DPI2016-80283-C2-2-R) - Period: from 2016 to 2020 - Principal investigator: Monllau García, Juan Carlos • Valoración pronóstica de los valores de los Productos Finales de la Glicación (AGEs) en enfermedades inmunomediadas y comparación con población general - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00059) - Period: from 2019 to 2021 - Principal investigator: Salman Monte, Tarek Carlos • Valoració pronòstica dels valors dels Productes Finals de la Glicació (AGEs) en malalties immunomediates i comparació amb població general - Financing institution: Societat Catalana de Reumatologia - Period: from 2018 to 2020 - Principal investigator: Pérez García, Carolina • Valoración pronóstica de los valores de los Productos Finales de la Glicación (AGEs) en enfermedades inmunomediadas y comparación con población general - Financing institution: Fundación Española de Reumatología - Period: from 2019 to 2020 - Principal investigator: Salman Monte, Tarek Carlos See all Projects

Clinical Trials Signed in 2019

• Práctica clínica habitual en España: evaluación del uso de apremilast en pacientes con artritis psoriásica, sin exposición previa a tratamientos biológicos (Estudio PREVAIL) - Protocol: CEL-APR-2018-01 - Sponsor: Celgene, S.L.U. - Budget: 4,482.6 € - Principal investigator: Beltrán Catalán, Emma • Estudio multinacional, prospectivo y observacional de la eficacia, la utilización de recursos sanitarios y los costes en pacientes con artritis reumatoide que reciben baricitinib, tratamientos modificadores de la enfermedad sintéticos dirigidos o biológicos - Protocol: I4V-MC-B009 - Sponsor: Eli Lilly and Company Limited - Budget: 11,090 € - Principal investigator: Pérez García, Carolina

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 141 Inflammatory and Cardiovascular Disorders Cell Research on Inflammation and Cartilage

• Estudio fase 3, aleatorizado, doble ciego, que compara risankizumab frente a placebo en pacientes con artritis psoriásica (AP) activa, que han tenido una historia previa de respuesta inadecuada o intolerancia a al menos un fármaco antirreumático modificador de la enfermedad (FAME) - Protocol: M16-011 - Sponsor: FER-MET-2019-01 - Budget: 103,544.41 € - Principal investigator: Beltrán Catalán, Emma • Registro nacional de pacientes con arteritis de células gigantes - Protocol: FER-MET-2019-01 - Sponsor: Fundación Española de Reumatología - Budget: 2,800 € - Principal investigator: Salman Monte, Tarek Carlos • Estudio en fase III, multicéntrico, aleatorizado, doble ciego, de 52 semanas de duración, para comparar la eficacia y la seguridad de GSK3196165 con placebo y con tofacitinib, en combinación con FARME sintéticos convencionales, en participantes con artritis reumatoide con actividad de moderada a intensa que han obtenido una respuesta inadecuada a los FARME sintéticos convencionales o a los biológicos - Protocol: 201791 - Sponsor: GlaxoSmithKline Research & Development Ltd - Budget: 49,164 € - Principal investigator: Pérez García, Carolina • Evaluación de la seguridad y tolerabilidad del sistema estimulador transcutáneo de Vorso para el tratamiento de pacientes con artritis reumatoide activa y una respuesta inadecuada a los fármacos biológicos modificadores de la enfermedad - Protocol: VC2018-2 - Sponsor: Vorso Corp - Budget: 14,700 € - Principal investigator: Pérez García, Carolina

Awards

• Raúl Torres Claramunt. Professor Palacios y Carvajal Award for the best oral communication presented by a resident doctor 2019. Sociedad Española de Cirugía de Cadera. June 2019.

142 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Clinical Illness

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Joan Ramon Masclans Enviz Francisco Álvarez Lerma (Researcher) [email protected] Yolanda Díaz Buendía (Researcher) María Pilar Gracía Arnillas (Researcher) Judith Marín Corral (Researcher) Purificación Pérez Terán (Researcher) Anna Salazar Degracia (Researcher) Antonia Vázquez Sánchez (Researcher) Clara Vilà Vilardell (Researcher) Ana Zapatero Ferrandiz (Researcher) Irene Dot Jordana (PhD Student) Ana Alabart Llinàs (Technician) Thais Guri López (Technician) Rosana Muñoz Bermúdez (Technician) Francisco José Parrilla Gómez (Technician) Marta Gas Amat (Research Assistant)

The Critical Illness Research Group (GREPAC) aims to elucidate the mechanisms involved in the onset and progression of different illnesses that cause a reversible dysfunction in one or more organs, placing the patient’s life at risk. Our research includes clinical research in patients, and also experimental models which allow us to study the molecular mechanisms involved in these processes and to identify therapeutic targets and new strategies.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 143 Inflammatory and Cardiovascular Disorders Critical Illness

GREPAC understands Critical Care research from a translational, clinical, and multidisciplinary perspective; therefore GREPAC conducts controlled clinical trials and observational projects of great interest, participating at all possible levels of commitment: as promoters, lead researchers and collaborators in multi-centre projects, as well as developing our own projects. The research group was recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a research group 2017-2020: Grup de Recerca en Patologia Crítica (SGR 200; Principal investigator: Judith Marín Corral).

Main Publications

• Subirà C, Hernández G, Vázquez-Sánchez A, Rodríguez-García R, González-Castro A, García C, Rubio O, Ventura L, López A, de la Torre MC, Keough E, Arauzo V, Hermosa C, Sánchez C, Tizón A, Tenza E, Laborda C, Cabañes S, Lacueva V, Fernández MM, Arnau A, Fernández R. Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA 2019; 321(22): 2175-2182. IF 51.273. D1. • Marín J, Dot I, Boguña M, Cecchini L, Zapatero A, Gracía-Arnillas MP, Pascual S, Vilà C, Castellví A, Pérez-Terán P, Gea J, Masclans JR. Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation. Int Care Med 2019; 45(4): 488-500. IF 18.967. D1. • Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernández G, García-de-Acilu M, Frat JP, Masclans JR, Ricard JD. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High Flow Therapy. Am J Respir Crit Care Med 2019; 199(11): 1368-1376. IF 16.494. D1. • Fernández-Barat L, Motos A, Panigada M, Álvarez-Lerma F, Viña L, López-Aladid R, Ceccato A, Bassi GL, Nicolau DP, López Y, Muñoz L, Guerrero L, Soy D, Israel T, Castro P, Torres A. Comparative efficacy of linezolid and vancomycin for endotracheal tube MRSA biofilms from ICU patients. Crit Care 2019; 23(1): 251. IF 6.959. Q1. • Luque S, Hope W, Campillo N, Muñoz-Bermúdez R, Sorli L, Barceló-Vidal J, González E, Álvarez-Lerma F, Masclans JR, Montero M, Horcajada JP, Grau S. Population pharmacokinetics of anidulafungin in critically ill patients. Antimicrob Agents Chemother 2019; 63(7): e00378-19. IF 4.715. Q1. See all Publications

144 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Critical Illness

Ongoing Research Projects

• Papel del eje IL-33 /ST2 en el diagnóstico, pronóstico y tratamiento del Síndrome de distrés respiratorio agudo - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI14/01420) - Period: from 2015 to 2019 - Principal investigator: Masclans Enviz, Joan Ramon • Mecanismos moleculares de disfunción diafragmática asociada a ventilación mecánica (VIDD) tras la utilización de modalidades ventilatorias controladas y espontáneas en un modelo humano - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/000025) - Period: from 2019 to 2021 - Principal investigator: Marín Corral, Judith; Masclans Enviz, Joan Ramon • Efecto de la ceftarolina sobre la respuesta immunomoduladora y anti-inflamatoria en un modelo murino de neumonía neumocócica - Financing institution: Sociedad Española de Neumología y Cirugía Torácica (SEPAR) - Period: from 2019 to 2022 - Principal investigator: Marín Corral, Judith See all Projects

Participation in Research Networks

• CIBERES: Ciber of Respiratory Diseases • HISPAFLOW: Spanish Group of Experts in High Flow Oxygen Therapy • Acute Respiratory Failure – Section Translational Biology Group of the European Society of Intensive Care Medicine (ESICM) • GETGAG: Spanish Working Group in Severe Influenza A • GLIMP: Global Initiative for MRSA Pneumonia

Clinical Trials Signed in 2019

• La oxigenoterapia de alto flujo como adyuvante en el tratamiento de la sepsis grave - Protocol: ALT-OXI-2018 - Sponsor: Althaia Xarxa Assistencial de Manresa Fundació Privada - Budget: No economic compensation - Principal investigator: Masclans Enviz, Joan

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 145 Inflammatory and Cardiovascular Disorders Critical Illness

• A Randomized, Active-Controlled Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-Calcoaceticus Complex - Protocol: CS2514-2017-0004 - Sponsor: Entasis Therapeutics - Budget: 28,730 €/patient (no patients included) - Principal investigator: Vázquez Sánchez, Antonia • Randomized, embedded, multifactorial adaptive platform trial for Community-acquired pneumonia - Protocol: REMAP-CAP - Sponsor: UMC Utrecht - Budget: 300 €/patient (1 patient included) - Principal investigator: Muñoz Bermúdez, Rosana

Theses

• Díaz Y. “UCI extendida” seguimiento de los pacientes críticos al alta del Servicio de Medicina Intensiva del Hospital del Mar. Universitat Autònoma de Barcelona - Director: Sancho Insenser, Joan Josep; Navarro Soto, Salvador; Masclans Enviz, Joan Ramon - Date of defense: 27/11/2019

Appointments

• Joan Ramon Masclans. Teaching Director of the PSMAR. February 2019. • Joan Ramon Masclans. Member of the Research Commission of the PSMAR. 2019. • Joan Ramon Masclans. Member of the Governing Board of the PSMAR. 2019. • Joan Ramon Masclans. President of the Comissió d’aturades of the PSMAR. 2019. • Joan Ramon Masclans. Secretary of the Organ and Tissue Donation and Transplant Commission • Recognition by the AQU of two research sections (six years). 5 July 2019.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Judith Marín Corral. Round table on the scientific career. BioJunior. 3 May 2019.

146 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Critical Illness

• Judith Marín Corral, Rosana Muñoz. Student of the Font del Ferro Institute visit the Laboratory of the Critical Illness Research Group. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 1 March 2019. • Judith Marín Corral. Talk at the Institut La Salle Barceloneta. International Day of Women and Girls in Science. 11 February 2019. • Rosana Muñoz, Anna Salazar, Purificación Pérez, Irene Dot. Visit to the Laboratory of the Critical Illness Research Group. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019. • Ana Zapatero. Donor’s Day event. Palau Robert, Barcelona. 4 June 2019. • Judith Marín Corral. Jornada “Posant el pacient en el centre de la recerca”. 21 January 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 147 Hepatologic Research

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Montserrat García Retortillo José Antonio Carrión Rodríguez (Researcher) mgarciaretortillo@ Susana Coll Estrada (PhD Student) parcdesalutmar.cat Maria Teresa Broquetas González (PhD Student) Núria Cañete Hidalgo (PhD Student) Marc Puigvehí Badosa (PhD Student) Rosa Fernández Rodríguez (Technician) Ana Viu Soto (Technician) Diego Lázaro Agudo (Research Assistant)

Since 2000, our research work has been dedicated to different clinical fields in Hepatology: the natural history of decompensated cirrhosis, ascites, renal insufficiency and infections; the virologic response to different therapeutic regimens against hepatitis C; adherence to hepatitis C treatment and the study, prevention and treatment of the psychiatric pathology associated with interferon and the progression of fibrosis in Hepatitis C, with or without HIV coinfection. Recently, in the era of direct antiviral agents (DAA), we have focused on the treatment of hepatitis C in special populations with many barriers to HCV eradication, such as people with addictions and mental disorders. We have also initiated different studies in hepatitis B (particularly regarding treatment adherence, predictors of treatment response and disease control and HBV reactivation),

148 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Hepatologic Research

hepatocellular carcinoma (biomarkers, natural history, and impact of different aetiologies) and non-alcoholic steatohepatitis (NASH). In 2019, our Group joined the LiverScreen Consortium, an international research group aimed to study the prevalence of liver fibrosis in high-risk groups within the general European population.

Main Publications

• Puigvehí M, de Cuenca B, Viu A, Diago M, Turnes J, Gea F, Pascasio JM, Lens S, Cabezas J, Badia E, Olveira A, Morillas RM, Torras X, Montoliu S, Cordero P, Castro JL, Salmerón J, Molina E, Sánchez-Ruano JJ, Moreno J, Antón MD, Moreno JM, de la Vega J, Calleja JL, Carrión JA. Eight weeks of Paritaprevir/r/Ombitasvir + Dasabuvir in HCV- genotype 1b with mild-moderate fibrosis: Results from a Real World Cohort. Liver Int 2019; 39(1): 90-97. IF 5.542. Q1. See all Publications

Ongoing Research Projects

• Screening for liver fibrosis. A population-based study in European countries. The “LiverScreen” project - Financing institution: Gilead Sciences (2018/8284/I) (2019); From January 2020: European Commission (European Union’s Horizon 2020 research and innovation programme) (847989) - Period: from 2019 to 2024 - Principal investigator: García Retortillo, Montserrat See all Projects

Participation in Research Networks

• The Liver Screen Consortium - Financing Institution: Gilead Sciences - Period: from 2019 to 2020 - Principal investigator: García Retortillo, Montserrat

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 149 Inflammatory and Cardiovascular Disorders Hepatologic Research

Clinical Trials Signed in 2019

• Blood Sample Collection to Evaluate Biomarkers for Hepatocellular Carcinoma - Protocol: 2017-01 - Sponsor: Exact Sciences Corporation - Budget: 6,071.62 € - Principal investigator: Coll Estrada, Susana • Cribaje de fibrosis hepática. Estudio poblacional en Europa. Proyecto “LiverScreen” - Sponsor: Fundació Clínic per a la Recerca Biomèdica - Principal investigator: García Retortillo, Montserrat

Outreach

Conferences, Seminars and Courses

• Montserrat Garcia Retortillo. Programa multidisciplinari per al tractament de l’hepatitis C en pacients amb addiccions: experiència de l’Hospital del Mar. L’hepatitis C a Barcelona. Objectiu: eliminació 2030. Agència de Salut Pública de Barcelona (ASPB), Barcelona, 15 October 2019.

Dissemination to Society and Initiatives of Citizen Participation

• MT Broquetas González. Malaltia hepàtica per greix, la nova epidèmia que afecta el fetge. Com detectar-la. Què s’ha de fer? Informació als pacients. I Congrés de Pacients Hepàtics. ASSCAT, AMTHC and Albi Espanya. Hotel d’Entitats Can Guardiola, Barcelona, 22 May 2019.

150 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Immunity and Infection

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members J o s é M i g u e l L ó p e z - B o t e t A r b o n a Elisenda Alari Pahissa (Researcher) [email protected] Ramón Gimeno Martínez (Researcher) Aura Muntasell Castellví (Researcher) Mireia Altadill Balsells (PhD Student) Michelle Ataya Fernández (PhD Student) Anna Rea (PhD Student) Gemma Heredia Díaz (Technician) Sara Raquel Santana Hernández (Technician)

The group integrates researchers from IMIM and Pompeu Fabra University (UPF) with extensive experience in the study of human Natural Killer (NK) cell biology. We currently collaborate on the development of two main research areas: • Characterization of NK cell receptors and their involvement in the response to human cytomegalovirus (HCMV) (J. M. López-Botet). We originally reported that human cytomegalovirus (HCMV) infection promotes to a variable extent a persistent reconfiguration of the human NK cell compartment. We are currently exploring the mechanisms that drive the development of this adaptive NK cell response, addressing its involvement in antiviral defense and putative implications in different settings (e.g. kidney transplantation, cancer, multiple sclerosis), in collaboration with clinical teams. • NK cells in cancer immunotherapy (A. Muntasell). NK cells can recognize and eliminate transformed cells while shaping the development of tumor-specific adaptive

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 151 Inflammatory and Cardiovascular Disorders Immunity and Infection

immunity. Several mechanisms decreasing NK cell function have been described in cancer patients. Our current projects are aimed at the identification of targetable checkpoints enhancing NK cell anti-tumor responses as well as at exploring the value of phenotypic, genetic and functional NK cell-related variables as biomarkers of response/resistance to treatment in breast and colorectal cancer patients, in collaboration with clinical teams.

Main Publications

• Muntasell A, Rojo F, Servitja S, Rubio-Pérez C, Cabo M, Tamborero D, Costa-García M, Martínez-García M, Menéndez S, Vázquez I, Lluch A, González-Pérez A, Rovira A, López-Botet M, Albanell J. NK Cell Infiltrates and HLA Class I Expression in Primary HER2+ Breast Cancer Predict and Uncouple Pathological Response and Disease-free Survival. Clin Cancer Res 2019; 25(5): 1535-1545. IF 8.911. Q1. • Muntasell A, Servitja S, Cabo M, Bermejo B, Pérez-Buira S, Rojo F, Costa-García M, Arpí O, Moraru M, Serrano L, Tusquets I, Martínez MT, Heredia G, Vera A, Martínez- García M, Soria L, Comerma L, Santana-Hernández S, Eroles P, Rovira A, Vilches C, Lluch A, Albanell J, López-Botet M. High Numbers of Circulating CD57+ NK Cells Associate with Resistance to HER2-Specific Therapeutic Antibodies in HER2+ Primary Breast Cancer. Cancer Immunol Res 2019; 7(8): 1280-1292. IF 8.619. Q1. • Deza G, March-Rodríguez A, Sánchez S, Ribas-Llauradó C, Soto D, Pujol RM, Gimeno R, Giménez-Arnau AM. Relevance of the Basophil High-Affinity IgE Receptor in Chronic Urticaria: Clinical Experience from a Tertiary Care Institution. J Allergy Clin Immunol Pract 2019; 7(5): 1619-1626. IF 7.550. Q1. • Costa-García M, Ataya M, Moraru M, Vilches C, López-Botet M, Muntasell A. Human Cytomegalovirus Antigen Presentation by HLA-DR+ NKG2C+ Adaptive NK Cells Specifically Activates Polyfunctional Effector Memory CD4+ T Lymphocytes. Front Immunol 2019; 10: 687. IF 4.716. Q2. See all Publications

Ongoing Research Projects

• Uncovering resistance to monoclonal antibodies in colorectal and breast cancer (J. Albanell, coordinator) - Financing institution: Proyecto Integrado de Excelencia. ISCIII (PIE 2015/00008) - Period: from 2015 to 2019 - Principal investigators: Muntasell, Aura; López-Botet Arbona, José Miguel

152 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Immunity and Infection

• Adaptive NK cell-mediated response to cytomegalovirus in the context of immunosuppression: clinical implications in renal transplantation - Financing institution: Fundació La Marató de TV3 (201822-10) - Period: from 2019 to 2021 - Principal investigator: López-Botet Arbona, José Miguel See all Projects

Participation in Research Networks

• Red Española de Esclerosis Múltiple (REEM) - Financing institution: Fondo de Investigación Sanitaria-ISCIII. Subprograma RETICS. RD16/0015/0011 - Period: from 2017 to 2020 - Principal investigators: López-Botet Arbona, José Miguel; Martínez Rodríguez, José Enrique

Theses

• Cabo M. Role of NK cells in the efficacy of anti-HER2 therapeutic antibodies in breast cancer: from biomarkers to functional checkpoints enhancing ADCC responses. Universitat Pompeu Fabra - Director: Muntasell Castellví, Aura - Date of defense: 08/11/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 153 Infectious Pathology and Antimicrobials

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Juan Pablo Horcajada Albert Alier Fabrego (Researcher) [email protected] Silvia Inés Gómez-Zorrilla Martín (Researcher) Alicia González Mena (Researcher) Santiago Grau Cerrato (Researcher) Ana Guelar Grimberg (Researcher) Roberto Carlos Güerri Fernández (Researcher) Hernando Knobel Freud (Researcher) Elisabet Lerma Chippirraz (Researcher) Emili Letang Jiménez de Anta (Researcher) Inmaculada López Montesinos (Researcher) Sònia Luque Pardos (Researcher) María Milagro Montero (Researcher) Luís Puig Verdié (Researcher) Francisca Sánchez Martínez (Researcher) M. Luisa Sorli Redó (Researcher) Judith Villar García (Researcher) María del Mar Arenas Miras (Technician) Itziar Arrieta Aldea (Technician) Marta de Antonio Cuscó (Technician) Núria Campillo Ambrós (Technician) Núria Carballo Martínez (Technician) Joan Gómez Junyent (Technician) Mònica Jorques Magrans (Technician)

154 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Infectious Pathology and Antimicrobials

The group is geared towards the clinical and epidemiological study of the most prevalent or transcendental infectious diseases in the community, such as HIV, pneumonia, urinary tract infections and tuberculosis. In the HIV arena the group is centered in comorbidities, inflammation and microbioma. The group also focuses on infections related to healthcare activities, including those caused by multidrug-resistant microorganisms, osteoarticular and prosthetic infections, and bacteraemia. A large proportion of the research done by the group focuses on antimicrobial therapy with new and old antibiotics, studying the pharmacokinetics and pharmacodynamics of these drugs and also studying new antimicrobial therapy strategies through clinical trials and observational studies carried out in the group, as main researchers, and collaborators in projects run by the group or multicenter projects.

Main Publications

• Horcajada JP, Montero M, Oliver A, Sorli L, Luque S, Gómez-Zorrilla S, Benito N, Grau S. Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. Clin Microbiol Rev 2019; 32(4): e00031-19. IF 17.75. D1. • Benítez-Cano A, de Antonio-Cuscó M, Luque S, Sorli L, Carazo J, Ramos-Delgado I, Bermejo S, Campillo N, Horcajada JP, Samsó E, Grau S. Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia. J Antimicrob Chemother 2019; 74(11): 3268-3273. IF 5.113. D1. • Lerma E, Pineda-Moncusí M, González-Mena A, Soldado-Folgado J, Knobel H, Trenchs-Rodríguez M, Díez-Pérez A, Brown TT, García-Giralt N, Güerri-Fernández R. Inflammation status in HIV-positive individuals correlates with changes in bone tissue quality after initiation of ART. J Antimicrob Chemother 2019; 74(5): 1381-1388. IF 5.113. D1. • Sorli L, Luque S, Li J, Campillo N, Danés M, Montero M, Segura C, Grau S, Horcajada JP. Colistin in the treatment of urinary tract infections caused by extremely drug- resistant Pseudomonas aeruginosa: dose is critical. J Infection 2019; 79(3): 253-261. IF 5.099. Q1. • Luque S, Hope W, Campillo N, Muñoz-Bermúdez R, Sorli L, Barceló-Vidal J, González E, Álvarez-Lerma F, Masclans JR, Montero M, Horcajada JP, Grau S. Population pharmacokinetics of anidulafungin in critically ill patients. Antimicrob Agents Chemother 2019; 63(7): e00378-19. IF 4.715. Q1. See all Publications

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 155 Inflammatory and Cardiovascular Disorders Infectious Pathology and Antimicrobials

Ongoing Research Projects

• Estudio de la toxicidad ósea asociada al tratamiento antirretroviral por microindentación y el papel de los miRNA como biomarcadores de afectación ósea - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/01860) - Period: from 2017 to 2020 - Principal investigator: Güerri Fernández, Roberto Carlos • Análisis de la actividad de diferentes opciones terapéuticas frente a “clones de alto riesgo” de Pseudomonas aeruginosa extremadamente resistente (XDR) aisladas en hospitales españoles mediante modelos PK-PD mono y bicompartimentales (Hollow fiber) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00669) - Period: from 2017 to 2020 - Principal investigator: Montero, María Milagro • Impacto clínico y microbiológico de los nuevos antipseudomónicos ceftolozano- tazobactam y ceftazidima-avibactam en las infecciones por Pseudomonas aeruginosa extremadamente resistente - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00251) - Period: from 2018 to 2020 - Principal investigator: Horcajada Gallego, Juan Pablo • Clinical and microbiological impact of the new antipseudomonal agents ceftolozane/ tazobactam and ceftazidime/avibactam in infections caused by high-risk clones of extensively drug-resistant (XDR) Pseudomonas aeruginosa in Spain. Correlation with in vitro results using a Hollow Fiber dynamic PK/PD model - Financing institution: Fundació La Marató de TV3 (201817-10) - Period: from 2019 to 2022 - Principal investigator: Horcajada Gallego, Juan Pablo • Estudio clínico y microbiológico sobre el impacto de la multirresistencia en la virulencia y en la respuesta del huésped a la infección por Pseudomonas aeruginosa - Financing institution: SEIMC (201817-10) - Period: from 2019 to 2021 - Principal investigator: Gómez-Zorrilla Martín, Silvia Inés See all Projects

156 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Infectious Pathology and Antimicrobials

Participation in Research Networks

• Red Española de Investigación en Patologías Infecciosas - Financing institution: Fondo de Investigación Sanitaria-ISCIII. Subprograma RETICS (RD16/0016/0015) - Period: from 2017 to 2021 - Principal investigator: Horcajada Gallego, Juan Pablo

Clinical Trials Signed in 2019

• Ensayo clínico abierto, aleatorizado y multicéntrico para comparar la eficacia, seguridad y tolerabilidad de una pauta de tratamiento TAF/FTC/DRV/cobi vs. ABC/3TC/DTG en pacientes infectados por el VIH-1 naïve de tratamiento antirretroviral - Protocol: Estudio SYMTRI - Sponsor: Asociación IRIS (Red de Investigación en Sida) - Budget: 2,066.1 € - Principal investigator: Knobel Freud, Hernando • Estudio en fase III para evaluar el efecto de la pitavastatina para prevenir los acontecimientos cardiovasculares en personas con infección por VIH-1 - Protocol: Reprieve - Sponsor: Neat Id Foundation - Budget: 26,480 € - Principal investigator: Knobel Freud, Hernando • Estudio aleatorizado, doble ciego, controlado con placebo, de búsqueda de dosis, en el que se evalúan la seguridad, la farmacocinética y el beneficio clínico de FLU-IGIV en pacientes hospitalizados con infección grave por el virus de la influenza A - Protocol: IA-001 - Sponsor: Emergent Biosolutions Canada Inc - Budget: 17,539.5 € - Principal investigator: Horcajada Gallego, Juan Pablo • Ensayo clínico de fase IV-III, con asignación aleatoria, controlado, abierto y multicéntrico, con dos grupos paralelos, para evaluar la eficacia de la combinación de cloxacilina y fosfomicina versus cloxacilina en monoterapia en el tratamiento de la bacteriemia por staphylococcus aureus sensible a la meticilina - Protocol: HUB-IDIBELL-SAFO-4.3.1 - Sponsor: Dr. Miquel Pujol Rojo (Hospital Universitari de Bellvitge) - Principal investigator: Gómez-Zorrilla Martín, Silvia Inés

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 157 Inflammatory and Cardiovascular Disorders Infectious Pathology and Antimicrobials

• Retrospective study to identify the incidence, risk factors and outcomes of prosthetic joint infection due to Staphylococcus aureus after primary knee or hip joint replacement - Protocol: FIS-MET-2019-01 - Sponsor: Fundacion Pública Andaluza para la Gestión de la Investigacion en Salud de Sevilla - Budget: 4,400 € - Principal investigator: Horcajada Gallego, Juan Pablo • Strategic Timing of AntiRetroviral Treatment (START Study) - Protocol: INSIGHT001: START-DAIDSID: 10619 - Sponsor: University of Minnesota - Budget: 3,862 € - Principal investigator: Knobel Freud, Hernando • Ceftolozano/tazobactam para el tratamiento de la bacteriemia por Pseudomonas aeruginosa multirresistente en pacientes neutropénicos con cáncer (estudio ZENITH) - Protocol: CGG-CEF-2018-01 - Sponsor: IDIBELL - Principal investigator: Montero, María Milagro • A Phase 3, Multicenter, Randomized, Double-blind Study of the Efficacy and Safety of Rezafungin for Injection versus Intravenous Caspofungin Followed by Optional Oral Fluconazole Step-down in the Treatment of Subjects with Candidemia and/or Invasive Candidiasis (The ReSTORE Study) - Protocol: CDIOI.IV.3.05 A3 - Sponsor: Cidara Therapeutics Inc. - Budget: 37,755 € - Principal investigator: Horcajada Gallego, Juan Pablo • Eficacia y tolerancia de 4 semanas de tedizolid en infección protésica articular tratadas con retirada del implante - Protocol: PROTEDI - Sponsor: Fundació Clínic per a la Recerca Biomèdica - Principal investigator: Sorli Redó, María Luisa

Theses

• Balcells E. Normalització segons edat i sexe del component força de l’escala de Constant de valoració de la funció de l’espatlla. Universitat Autònoma de Barcelona - Directors: Luís Puig Verdié; Daunis, J. - Date of defense: 18/09/2019

158 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Infectious Pathology and Antimicrobials

• Esteve-Palau E. Impacte clínic i econòmic de les infeccions urinàries per E. Coli Blee i de l’aplicació d’un programa d’optimització d’antimicrobians (PROA) en el seu abordatge terapèutic. Universitat Autònoma de Barcelona - Directors: Horcajada Gallego, Juan Pablo; Grau Cerrato, Santiago - Date of defense: 14/01/2019 • Lerma E. Estudio del impacto de la infección por VIH en el metabolismo óseo. Universitat Autònoma de Barcelona - Directors: Díez-Pérez A; Knobel Freud, Hernando - Date of defense: 03/06/2019 • Mari-Molina R. Cutibacterium acnes després de la preparació quirúrgica de les artroplàsties d’espatlla: de la pell als teixits profunds. Universitat Autònoma de Barcelona - Directors: Torrens, C; Puig Verdié, Luís - Date of defense: 30/09/2019

Outreach

Conferences, Seminars and Courses

• Curso Intensivo de Terapia Antimicrobiana “Dr. Drobnic”. Hospital del Mar, Barcelona, 25-29 March 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Juan Pablo Horcajada. Les infeccions incurables ja són aquí. Science Festival 2019. Barcelona, 27 October 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 159 Inflammatory and Neoplastic Dermatological Diseases

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Ramon Maria Pujol Vallverdú Luis Gustavo Deza Vargas (Researcher) [email protected] Ana María Giménez Arnau (Researcher) María Inmaculada Hernández Muñoz (Researcher) Gemma Martín Ezquerra (Researcher) Sònia Segura Tigell (Researcher) Laia Curto Barredo (PhD Student) Marta Ferran Farrés (PhD Student) Evelyn Andrades López (Technician) Mónica Hijós Rullo (Technician) Clara Ribas Llauradó (Technician) Sílvia Sánchez Serrano (Technician)

The Research Group on Inflammatory and Neoplastic Dermatological Diseases is composed of dermatologists, biologists and immunologists, connecting the bedside with the bench, which is a clear example of translational research. The group includes two different lines of investigation: • The study of inflammatory dermatological diseases, mainly psoriasis, urticaria and bullous diseases: A) In psoriasis, we have developed a new in-vitro model which allows us to study the pathogenic mechanisms involved in early stages of the disease in different

160 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

psoriasis phenotypes, consisting of the coculture of circulating CLA+ T cells (with cutaneous tropism), together with autologous epidermic cells from psoriatic patients, activated with Streptococcus pyogenes (SP) extract, a well-known psoriasis trigger. In addition, we focus on the characterization of T cell response in psoriasis. B) In urticaria, the ongoing projects are related to the definition of clinical phenotypes of the diseases along with transcriptome analysis of severe chronic spontaneous urticaria (CSU) and cold urticaria, and the detection of potential biomarkers of clinical evolution and response to treatment. C) In autoimmune bullous diseases, the studies focus on the role of the innate immune system in the pathogenetic mechanisms of acquired epidermolysis bullosa. • Research into the pathogenetic mechanisms of progression and immunological response to nonmelanoma skin cancer. Our group also studies the link between inflammation and cutaneous squamous cell carcinoma (SCC). Our preliminary results show that metastatic SCC displays enhanced Polycomb levels (an epigenetic repressor family) and that Polycomb represses cytokine/chemokine expression in SCC cells. Our working hypothesis is that Polycomb repression of cytokine/chemokine expression in SCC blocks differentiation and function of the myeloid inflammatory component and favors a protumoral immune response.

Main Publications

• Maurer M, Giménez-Arnau AM, Sussman G, Metz M, Baker DR, Bauer A, Bernstein JA, Brehler R, Chu CY, Chung WH, Danilycheva I, Grattan C, Hébert J, Katelaris C, Makris M, Meshkova R, Savic S, Sinclair R, Sitz K, Staubach P, Wedi B, Löffler J, Barve A, Kobayashi K, Hua E, Severin T, Janocha R. Ligelizumab for Chronic Spontaneous Urticaria. New Engl J Med 2019; 381(14): 1321-1332. IF 70.67. D1. • Deza G, March-Rodríguez A, Sánchez-Serrano S, Ribas-Llauradó C, Soto D, Pujol RM, Gimeno R, Giménez-Arnau AM. Relevance of the basophil high-affinity IgE receptor in chronic urticaria: Clinical experience from a tertiary care institution. J Allergy Clin Immunol Pract 2019; 7(5): 1619-1626.e1. IF 7.55. Q1. • Wilkinson M, Gonçalo M, Aerts O, Badulici S, Bennike NH, Bruynzeel D, Dickel H, García-Abujeta JL, Giménez-Arnau AM, Hamman C, Isaksson M, Johansen JD, Mahler V, Niklasson B, Orton D, Pigatto P, Ponyai G, Rustemeyer T, Schuttelaar MLA, Spiewak R, Thyssen JP, Uter W. The European baseline series and recommended additions: 2019. Contact Dermatitis 2019; 80(1): 1-4. IF 5.504. D1. • Balato A, Raimondo A, Arenberger P, Bruze M, Czarnecka-Operacz M, Johanssen JD, Gonçalo M, Ranki A, Uter W, Wilkinson M, Ayala F, John SM, Giménez-Arnau AM, Gollnick H. The role of the dermatologist in the immune-mediated/allergic diseases - position statement of the EADV task force on contact dermatitis, EADV task force on

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 161 Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

occupational skin diseases, UEMS-EBDV subcommission allergology and European Dermatology Forum. J Eur Acad Dermatol Venereol 2019; 33(8): 1459-1464. IF 5.113. D1. • García-Díez I, Hernández-Muñoz I, Hernández-Ruiz E, Nonell L, Puigdecanet E, Bódalo-Torruella M, Andrades E, Pujol RM, Toll A. Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients. Genes Chromosomes Cancer 2019 Mar; 58(3): 164-174. IF 3.44. D1. See all Publications

Ongoing Research Projects

• Regulación epigenética de la función inflamatoria del componente epitelial en la progresión metastática del carcinoma escamoso cutáneo (CEC) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00236) - Period: from 2016 to 2019 - Principal investigator: Hernández Muñoz, María Inmaculada • Caracterización de la respuesta immune frente a Streptococcus pyogenes a través de los linfocitos T CLA+ en la psoriasis guttata y en la psoriasis en placas - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00532) - Period: from 2017 to 2020 - Principal investigator: Pujol Vallverdú, Ramon Maria • Inmunofenotipificación y caracterización genética de la urticaria crónica por contacto al frío o “urticaria a frigore” - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00198) - Period: from 2018 to 2020 - Principal investigator: Giménez Arnau, Ana María • Estudio funcional del efecto de inhibición farmacológica en modelo in vivo murino de células primarias de síndrome de Sézary (linfoma cutáneo de células T) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00021) - Period: from 2019 to 2021 - Principal investigator: Gallardo Hernández, Fernando • Mecanismos epigenéticos implicados en la progresión metastática del carcinoma escamoso cutáneo (CEC): papel de la disqueratina y los RNAs no codificantes de pequeño tamaño - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00065) - Period: from 2019 to 2021 - Principal investigator: Hernández Muñoz, María Inmaculada See all Projects

162 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

Clinical Trials Signed in 2019

• Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo, de 52 semanas de duración para demostrar la eficacia, seguridad y tolerabilidad de inyecciones subcutáneas de secukinumab con autoinyectores de 2 ml (300 mg) en pacientes adultos con psoriasis en placas de moderada a grave – MATURE - Protocol: CAIN457A2325 - Sponsor: Novartis Farmacéutica, S.A. - Budget: 15,680.01€ - Principal investigator: Ferran Farrés, Marta • A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Combination with Topical Corticosteroids in Adult Patients with Moderate to Severe Atopic Dermatitis - BREEZE-AD7 - Protocol: I4V-MC-JAIY - Sponsor: Lilly, S.A.U. - Budget: 47,140 € - Principal investigator: Curto Barredo, Laia • Estudio de búsqueda de dosis, doble ciego y controlado con placebo para evaluar la seguridad y eficacia de tezepelumab en monoterapia o en combinación con corticosteroides tópicos en la dermatitis atópica de moderada a grave - Protocol: 20170755 - Sponsor: Amgen, SA - Budget: 42,545 € - Principal investigator: Curto Barredo, Laia • Estudio fase 2b, de búsqueda de dosis, multicéntrico, aleatorizado, doble ciego, controlado con placebo, para investigar la eficacia, seguridad y tolerabilidad de LOU064 en pacientes adultos con urticaria crónica espontánea inadecuadamente controlados con antihistamínicos H1 - Protocol: CLOU064A2201 - Sponsor: Novartis Farmacéutica, S.A. - Budget: 22,000 € - Principal investigator: Giménez Arnau, Ana María • A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects with Moderate to Severe Atopic Dermatitis - Protocol: M18-891 - Sponsor: Abbvie Spain, S.L.U. - Budget: 53,895 € - Principal investigator: Pujol Vallverdú, Ramon Maria

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 163 Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

• Estudio aleatorizado, doble ciego, controlado con placebo, multicéntrico para evaluar la eficacia y seguridad del inhibidor oral de BTK PRN1008 en el pénfigo moderado a grave - Protocol: PRN1008-012 - Sponsor: Principia Biopharma - Budget: 11,851.26 € - Principal investigator: Curto Barredo, Laia • Estudio de fase 3, multicéntrico, doble ciego, en el que se evalúan la seguridad y la eficacia a largo plazo de baricitinib en pacientes adultos con dermatitis atópica - Protocol: I4V-MC-JAHN - Sponsor: Lilly, S.A.U. - Budget: 85,670 € - Principal investigator: Curto Barredo, Laia • Estudio de resultados sanitarios en la psoriasis (PSoHO): estudio observacional internacional de resultados sanitarios durante 3 años sobre el tratamiento biológico de la psoriasis en placas de moderada a grave - Protocol: I1F-MC-B007 - Sponsor: Eli Lilly and Company Limited - Budget: 13,370 € - Principal investigator: Ferran Farrés, Marta • Un estudio en fase 2b/3 aleatorizado, con enmascaramiento doble, controlado con placebo, de intervalos de dosis, para investigar la eficacia y seguridad de PF- 06651600 en sujetos adultos y adolescentes con alopecia areata (AA) con una pérdida de cabello en el cuero cabelludo del 50% o más - Protocol: B7981015 - Sponsor: Pfizer, Inc - Budget: 33,798.5 € - Principal investigator: Pujol Vallverdú, Ramon Maria • Estudio de extensión multicéntrico y abierto para evaluar la seguridad y tolerabilidad a largo plazo de LOU064 en pacientes elegibles con urticaria crónica espontánea que hayan participado en estudios anteriores con LOU064 - Protocol: CLOU064A2201E1 - Sponsor: Novartis Farmacéutica, S.A. - Budget: 31,825 € - Principal investigator: Giménez Arnau, Ana María

164 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

• Efectividad de la PUVA-terapia local en afecciones palmoplantares: estudio observacional, prospectivo y multicéntrico del Grupo Español de Fotobiología (GEF) - Protocol: MAR-MET-2015-01 - Sponsor: Rodríguez Granados, M. Teresa - Budget: No economic compensation - Principal investigator: Ferran Farrés, Marta • A Multicenter, Long-Term Extension to Evaluate the Long-Term Safety and Maintenance of Treatment Effect of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis - Protocol: I6T-MC-AMAH - Sponsor: Lilly, S.A.U. - Budget: 120,785.01 € - Principal investigator: Pujol Vallverdú, Ramon Maria • An exploratory, multicenter, randomized, open-label with blind evaluation, active- controlled study to evaluate the safety and efficacy of Keramod® (imiquimod 50 mg/g, Gel) compared with Aldara® (imiquimod 50 mg/g, Cream) for the treatment of actinic keratosis in adults - Protocol: OJ-KDC01 - Sponsor: Laboratorios Ojer Pharma, S.L. - Budget: 57,052 € - Principal investigator: Segura Tigell, Sònia • Estudio observacional para evaluar la efectividad descriptiva en el mundo real en pacientes con psoriasis en placa de moderada a grave tratados con brodalumab - Protocol: LEO-BRO-2019-01 (NIS-KYNTHEUM-1466) - Sponsor: Leo Pharma - Budget: 15,286.2 € - Principal investigator: Ferran Farrés, Marta • Estudio de extensión de retirada, aleatorizado, doble ciego y multicéntrico para demostrar la eficacia, seguridad y tolerabilidad a largo plazo de secukinumab subcutáneo en pacientes con hidradenitis supurativa de moderada a grave - Protocol: CAIN457M2301E1 - Sponsor: Novartis Farmacéutica S.A. - Budget: 25,170 € - Principal investigator: Martín Ezquerra, Gemma

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 165 Inflammatory and Cardiovascular Disorders Inflammatory and Neoplastic Dermatological Diseases

• Estudio de fase III, abierto, multicéntrico, a largo plazo, para investigar la seguridad y la eficacia de PF-06651600 en participantes adultos y adolescentes con alopecia areata - Protocol: B7981032 - Sponsor: Pfizer INC - Budget: 38,336.1 € - Principal investigator: Pujol Vallverdú, Ramon Maria • Estudio retrospectivo multicéntrico de práctica clínica habitual en paciente con psoriasis moderada a grave tratados con Guselkumab - Protocol: JAN-GUS-2019-02 / CNTO1959PSO4010 - Sponsor: Janssen-Cilag - Budget: 1,800 € - Principal investigator: Pujol Vallverdú, Ramon Maria • Estudio aleatorizado, doble ciego, multicéntrico que evalúa la eficacia a corto (16 semanas) y largo plazo (hasta un año), la seguridad y la tolerabilidad de 2 regímenes de dosis de secukinumab subcutáneo, en pacientes adultos con hidradenitis supurativa de moderada a severa (SUNRISE) - Protocol: CAIN457M2302 - Sponsor: Novartis Farmacéutica S.A. - Budget: 46,400 € - Principal investigator: Martín Ezquerra, Gemma; Ferran Farrés, Marta

Awards

• M. Ferran, E. Ruiz-Romeu, C. de Jesús, A. Celada, R.M. Pujol, L.F. Santamaria-Babí. La inhibición de PD-L1 da lugar a una respuesta IL-17 en los cocultivos de linfocitos T CLA+ con células epidérmicas activados por S. pyogenes en psoriasis. Reunión del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología. Madrid, January 20th 2019. Award to best poster presentation.

166 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Kidney Disease

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Julio Pascual Santos Carlos Enrique Arias Cabrales (Researcher) [email protected] Clara Barrios Barrera (Researcher) Marta Crespo Barrio (Researcher) Javier Gimeno Beltrán (Researcher) Anna Oliveras Serrano (Researcher) María José Pérez Sáez (Researcher) Dàlia Raïch Regué (Researcher) María Dolores Redondo Pachón (Researcher) Marta Riera Oliva (Researcher) Eva Rodríguez García (Researcher) Laia Sans Atxer (Researcher) Susana Vázquez González (Researcher) Carla Cristina Burballa Tàrrega (PhD Student) Sílvia Collado Nieto (PhD Student) Laura Llinàs Mallol (PhD Student) Vanesa Palau González (PhD Student) Sara Álvarez Morales (Technician) David Benito Guasch (Technician) Anna Buxeda Porras (Technician) Anna Faura Vendrell (Technician) Montserrat Folgueiras López (Technician) Adriana Sierra Ochoa (Technician) Maria Vera Casanova (Techncian)

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 167 Inflammatory and Cardiovascular Disorders Kidney Disease

The Kidney Research Group (GREN) at IMIM belongs to the Nephrology Department of Parc de Salut Mar, Barcelona, Spain. The Nephrology Department covers structured assistance to the renal patient in four areas: clinical nephrology, kidney transplantation, chronic kidney disease and hypertension-cardiovascular risk. The department has made a particular effort in the area of kidney transplantation, covering all transplant modalities (deceased donor, living donor, sensitized patients, ABO-incompatible, etc). GREN also has a basic-translational lab, in which a number of biologists (pre and postdoc) work together with nephrology physicians to achieve research objectives in different specialized areas. It belongs to the Red de Investigación Renal (renal research network - REDinREN) and is recognized by AGAUR. The group aims to clarify mechanisms involved in the onset and progression of kidney diseases through preclinical research into in vivo and in vitro models. This makes it possible to study the molecular mechanisms involved, and will thus help us to identify the treatment targets and new strategies against kidney disease. We also aim to study new treatment targets and strategies in depth by performing controlled clinical trials and observational projects of great interest, while securing all levels of possible commitment: promoters, main researchers, collaboration in multicenter projects and own projects. Our research focuses mainly on three research areas: diabetic kidney disease and early markers of chronic kidney disease (C. Barrios PI16/00620), resistant hypertension (A. Oliveras EC11-426 and PI16/01356), new pathogenetic and therapeutic targets in the field of kidney transplantation (J. Pascual and M. Crespo PI13/00598, PI16/00617) and kidney transplantation in old and frail patients (J. Pascual, PI19/0037).

Main Publications

• Berger SP, Sommerer C, Witzke O, Tedesco H, Chadban S, Mulgaonkar S, Qazi Y, de Fijter JW, Oppenheimer F, Cruzado JM, Watarai Y, Massari P, Legendre C, Citterio F, Henry M, Srinivas TR, Vincenti F, Gutiérrez MPH, Martí AM, Bernhardt P, Pascual J; TRANSFORM investigators. Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study. Am J Transplant 2019; 19(11):3018-3034. IF 7.163. D1. • Montero N, Quero M, Melilli E, Pérez-Sáez MJ, Redondo-Pachón D, Bestard O, Crespo M, Cruzado JM, Pascual J. Mammalian Target of Rapamycin Inhibitors Combined With Calcineurin Inhibitors as Initial Immunosuppression in Renal Transplantation: A Meta-analysis. Transplantation 2019; 103(10):2031-2056. IF 4.743. D1. • Llinàs-Mallol L, Redondo-Pachón D, Pérez-Sáez MJ, Raïch-Regué D, Mir M, Yélamos J, López-Botet M, Pascual J, Crespo M. Peripheral blood lymphocyte subsets change after steroid withdrawal in renal allograft recipients: a prospective study. Sci Rep 2019; 9(1):7453. IF 4.011. Q1.

168 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Kidney Disease

• Palau V, Pascual J, Soler MJ, Riera M. Role of ADAM17 in kidney disease. Am J Physiol Renal Physiol 2019; 317(2):F333-F342- IF 3.323. Q1. • Buxeda A, Redondo-Pachón D, Pérez-Sáez MJ, Bartolomé Á, Mir M, Pascual-Dapena A, Sans A, Duran X, Crespo M, Pascual J. Gender differences in cancer risk after kidney transplantation. Oncotarget 2019; 10(33):3114-3128. See all Publications

Ongoing Research Projects

• Adherencia terapéutica en Hipertensión Arterial no controlada: detección selectiva y eficacia y efectividad de un programa para mejorar el cumplimiento (Athan) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/01356) - Period: from 2017 to 2019 - Principal investigator: Oliveras Serrano, Anna • Anticuerpos HLA y no HLA en el rechazo del trasplante renal y mecanismos de lesión - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00617) - Period: from 2017 to 2020 - Principal investigator: Pascual Santos, Julio • Estudio de metabolómica y glicómica para la identificación de biomarcadores de función y daño renal en la diabetes mellitus tipo 2 - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00620) - Period: from 2017 to 2021 - Principal investigator: Barrios Barrera, Clara • Estudi multicèntric, aleatoritzat per avaluar l’eficàcia de la individualització del risc immunològic basat en biomarcadors selectius (Disparitat d’Eplets HLA i Elispot IFN-Y), per optimitzar el tractament immunosupressor en pacients trasplantats renals de donant viu (BIOIMMUN) - Financing institution: Departament de Salut de la Generalitat de Catalunya (SLT002/16/00183) - Period: from 2017 to 2019 - Principal investigator: Crespo Barrio, Marta See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 169 Inflammatory and Cardiovascular Disorders Kidney Disease

Participation in Research Networks

• Red de Investigación Renal (REDINREN) - Financing institution: Fondo de Investigación Sanitaria-ISCIII. Subprograma RETICS. RD16/0009/0013 - Period: from 2017 to 2022 - Principal investigator: Pascual Santos, Julio

Clinical Trials Signed in 2019

• Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo en dos etapas para caracterizar la eficacia, seguridad, tolerabilidad y farmacocinética de GZ/ SAR402671 en pacientes con Enfermedad Renal Poliquística Autosómica Dominante (ERPAD) en riesgo de progresión rápida - Protocol: EFC15392 - Sponsor: Sanofi Aventis, SA - Budget: 182,475 € - Principal investigator: Sans Atxer, Laia • A Phase 3b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of TRC101 in Delaying Chronic Kidney Disease Progression in Subjects with Metabolic Acidosis - Protocol: TRCA-303 (VALOR-CKD) - Sponsor: TRICIDA - Budget: 37,015 € - Principal investigator: Collado Nieto, Silvia • Efecto de semaglutida en comparación con placebo sobre la progresión de la insuficiencia renal en sujetos con diabetes de tipo 2 y nefropatía crónica - Protocol: NN9535-4321 - Sponsor: Novo Nordisk A/S - Budget: 95,333.26 € - Principal investigator: Pascual Santos, Julio • A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients - Protocol: VKTX01 - Sponsor: Vitaeris - Budget: 166,956.2 € - Principal investigator: Crespo Barrio, Marta

170 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Kidney Disease

• Semaglutide cardiovascular outcomes trial in patients with type 2 diabetes (SOUL) - Protocol: EX9924-4473 (SOUL) - Sponsor: Novo Nordisk Pharma S.A - Budget: 153,000 € - Principal investigator: Pascual Santos, Julio • Ensayo en Fase III Sobre la Eficacia y Seguridad del Metilbardoxolona en Pacientes con Enfermedad Poliquística Renal Autosómica Dominante - Protocol: 402-C-1808 - Sponsor: REATA - Budget: 42,515.01 € - Principal investigator: Sans Atxer, Laia

Theses

• Otero S. Marcadores alternativos de daño renal asociado a la diabetes. Universitat Autònoma de Barcelona - Directors: Barrios Barrera, Clara; Pascual Santos, Julio - Date of defense: 25/04/2019

Awards

• Marta Crespo. Premi a l’excel·lència investigadora del COMB. December 2019. • M. Fernández, Y Martínez, E. Junyent, S. Collado. Resultados de la implantación de la consulta de ayuda a la decisión en la elección de terapia renal sustitutiva. XLIV Congreso Nacional de la SEDEN. Premio SEDEN Enfermedad Renal Crónica Avanzada. Coruña, 8-10 October 2019. • ara Núñez, Anna Buxeda, Laia Sans, Susana Vázquez, Julio Pascual, Anna Oliveras. XXVI Reunió de la Societat Catalana d’Hipertensió Arterial – XXXII Jornades Catalanes sobre Hipertensió Arterial. XX Award for best clinical case. 11 December 2019. • P. Fernández-Llama, P. Armario, À. de la Sierra, A. Oliveras. Research award in Nephrology, 2019. Sociedad Española de Nefrología. September 2019.

Appointments

• Marta Crespo. Member of the board of the working group DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) of the European Renal Association – European Dialysis and Transplant Association (ERA- EDTA). 2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 171 Inflammatory and Cardiovascular Disorders Kidney Disease

Outreach

Conferences, Seminars and Courses

• Marta Crespo, María José Pérez Sáez. Coordinators and teachers. Curso de Trasplante para Residentes de Nefrología. Sociedad Española de Nefrología (SEN). Alcalá de Henares, 14-16 November 2019. • Marta Crespo, Dolores Redondo. Coordinators. Workshop HLA. XLIX Congreso de la Sociedad Española de Nefrología. A Coruña, 5-8 October 2019. • María José Pérez-Sáez. Outcomes of frail patients after kidney transplantation. 56th EDTA Congress. Budapest, Hungary. 13-16 June 2019. • María José Pérez-Sáez. I Curso de Trasplante para enfermeras de Nefrología. Barcelona, 21-28 March 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Marta Crespo. Jornada Trasplante Renal de Donante Vivo. Hospital del Mar. May 2019. • Marta Crespo. Què representa per a l’investigador posar en marxa el seu projecte de recerca gràcies a la suma d’esforços dels donants a La Marató, la primera iniciativa solidària del país? Masterclass de La Marató de TV3. Campus Hospital del Mar. 9 April 2019.

172 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Esther Barreiro Portela Víctor Curull Serrano (Researcher) [email protected] Marisol Domínguez Álvarez (Researcher) María Guitart de la Rosa (Researcher) Lara Pijuan Andújar (Researcher) Alberto Rodríguez Fuster (Researcher) Albert Sánchez Font (Researcher) Maria Pérez Peiró (PhD Student)

Our research is based on the use of patients from clinical settings, animal models of disease, and in vitro primary cultures. We use all kinds of biochemical and cellular and molecular biology techniques (RT-PCR, immunoblotting, immunohistochemistry, 2-D electrophoresis, proteomics analysis, ELISA, activity assays, mitochondrial respiration, flow cytometry, etc.) in order to explore the target mechanisms of our research. The most relevant achievements of our research have been the following: demonstrating that oxidative and nitrosative stress, ubiquitin-proteasome system, NF-kB and FoxO signaling, alterations of epigenetic regulation, and loss of muscle- specific proteins are important players in COPD- and lung cancer-associated cachexia, whereas muscle inflammation does not play a role in this process.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 173 Inflammatory and Cardiovascular Disorders Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer

Moreover, in the last five years, we have started a new avenue of research focusing on the underlying biology that accounts for the greater susceptibility of patients with chronic respiratory diseases (e.g. COPD) to developing lung tumors. We have demonstrated that increased oxidative stress, inflammatory cytokines and disruption of epigenetic regulation are involved in the greater susceptibility of patients with COPD to developing lung cancer. Finally, we are currently undertaking a new line of research in muscle regeneration. Our first relevant achievement in this area has been the demonstration that there is a decline in the number of satellite cells (SC) following hindlimb immobilization in mice together with an upregulation of markers of SC activation, suggesting that fusion to existing myofibers takes place during unloading. Muscle recovery induces a significant rise in muscle precursor cells and regeneration events along with reduced SC-activation expression markers and a concomitant rise in terminal muscle differentiation expression.

Main Publications

• Tang J, Ramis-Cabrer D, Xuejie W, Barreiro E. Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events. Cancers 2019; 11(9): E1301. IF 6.162. Q1. • Barreiro E, Wang X, Tang J. COPD: preclinical models and emerging therapeutic targets. Expert Opin Ther Targets 2019; 23(10): 829-838. IF 4.621. Q1. • Barreiro E, Salazar-Degracia A, Sancho A, Gea J. Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases. J Cell Physiol 2019; 234(7): 11315-11329. IF 4.522. Q1. • Busquets S, Pérez-Peiró M, Salazar-Degracia A, Argilés JM, Serpe R, Rojano-Toimil A, López-Soriano FJ, Barreiro E. Differential structural features in soleus and gastrocnemius of carnitine-treated cancer cachectic rats. J Cell Physiol 2020; 235(1): 526-537. IF 4.522. Q1. • Salazar-Degracia A, Granado-Martínez P, Millán-Sánchez A, Tang J, Pons-Carreto A, Barreiro E. Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice. J Cell Physiol 2019; 234(10): 18041-18052. IF 4.522. Q1. See all Publications

174 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer

Ongoing Research Projects

• Papel del estrés del retículo endoplásmico y PARP en el potencial regenerativo muscular en la sarcopenia asociada a la EPOC y la caquexia cancerosa: implicaciones terapéuticas - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00075) - Period: from 2019 to 2021 - Principal investigator: Barreiro Portela, Esther See all Projects

Participation in Research Networks

• Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES) - Financing institution: Fondo de Investigación Sanitaria. Subprograma CIBER CB06/06/0043 - Period: from 2006 to 2020 - Collaborating investigator: Barreiro Portela, Esther - Principal investigator: Gea Guiral, Joaquim

Clinical Trials Signed in 2019

• Heterogeneidad en la susceptibilidad a la infección en las bronquiectasias: Interacción huésped-microbioma y su valor predictivo en la práctica clínica. Proyecto BronchI- Omics - Protocol: BronchI-Omics - Sponsor: Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol - Principal investigator: Barreiro Portela, Esther

Theses

• Anna Salazar Degracia. Mechanisms of muscle wasting in cachexia models: therapeutic implications. Universitat Pompeu Fabra - Director: Barreiro Portela, Esther - Date of defense: 15/04/2019 • Daniel Ramis Cabré. From chronic obstructive pulmonary disease to lung cancer: an immunologic approach. Universitat Pompeu Fabra - Director: Barreiro Portela, Esther - Date of defense: 11/07/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 175 Inflammatory and Cardiovascular Disorders Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer

Awards

• L Mañas-García, J Deschevrel, M Guitart, A Penedo, E Barreiro. Contribution of prolonged immobilization and lung cancer cachexia to muscle mass loss in mice: Implications to the clinics in hospitalized patients. 3a Jornada de Recerca Bàsica en Pneumologia, XXXVII Diada Pneumològica. Terrassa, Barcelona, April 2019. Award for the best communication. • J Tang, D Ramis Cabrer, V Curull Serrano, M Mateu-Jimenéz, L Pijuan, A Rodríguez- Fuster, R Aguiló Espases, E Barreiro. Immune profile and survival in lung cancer patients: influence of underlying COPD. 11 Jornadas de Formación del CIBERES. Madrid, October 2019. Award for the best communication.

Appointments

• Member of the Planning Committee for the ATS Assembly on ATS Respiratory Structure and Function (RSF), American Thoracic Society International Conference, USA. From May 2018. • Member of the Steering Committee of the Asociación de Médicos Gallegos (ASOMEGA), Spain. From May 2018. • Member of the Gender Policy Committee, Department of Experimental Sciences and Health, Universitat Pompeu Fabra. Barcelona. From June 2018.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Laura Mañas, María Guitart. Visit to the Laboratory of the Research Group of Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019.

176 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Musculoskeletal Research

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Francesc Xavier Nogués Solan Adolf Díez Pérez (Researcher) [email protected] Leonardo Mellibovski Saidler (Researcher) Guillem Saló Bru (Researcher) Isabel Aymar Fábrega (Technician) Carme Giménez Argente (Technician) Abora Rial Villavecchia (Technician) Carme Sánchez Galiano (Research Assistant)

Our research focuses on the study of musculoskeletal disorders and the underlying mechanisms of bone pathophysiology. The group covers three main areas of research: genetics, epidemiology, and bone quality. In the genetics field, we are exploring the genetic basis of bone disorders for both complex diseases such as osteoporosis and rare disorders such as monogenic skeletal dysplasias. In this line, we are active members of the GEMSTONE, a European COST action for the study of the Genomics of MusculoSkeletal traits. At population level, we are working in the epidemiology of bone outcomes using several cohorts: BARCOS, SIDIAP and B-ABLE, currently involved in ongoing studies related to bone health and frailty. The BARCOS cohort also belongs to the international GEFOS/ GENOMOS consortium, which has performed several genome-wide studies and metanalyses. B-ABLE is a cohort of postmenopausal women with early breast cancer

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 177 Inflammatory and Cardiovascular Disorders Musculoskeletal Research

treated with aromatase inhibitors. SIDIAP is a database that provides anonymized clinical information as coded by primary care practitioners in Catalonia, covering more than 7 million patients. Moreover, we started a new frailty cohort (CohorFES), involving a number of Spanish centres in CIBERFES with the aim of finding trajectories to explain the worsening process of frailty. Our research also encompasses a number of diseases and therapies that affect bone metabolism as a secondary outcome. These include HIV infection and antiretroviral therapies, atypical fractures due to bisphosphonate treatment and other diseases with bone involvement. Our group is a leading research group in the development of a novel, hand-held Reference Point Indentation (RPI) instrument, Osteoprobe®, which measures bone quality. Finally, our group is also working on the design of biomaterials and scaffolds for promoting the biointegration of implants in osseous and soft tissues.

Main Publications

• Díez-Pérez A, Marín F, Eriksen EF, Kendler DL, Krege JH, Delgado-Rodríguez M. Effects of teriparatide on hip and upper limb fractures in patients with osteoporosis: A systematic review and meta-analysis. Bone. 2019; 120: 1-8. IF 4.36. Q1. • Pineda-Moncusí M, Servitja S, Tusquets I, Díez-Pérez A, Rial A, Cos ML, Campodarve I, Rodríguez-Morera J, García-Giralt N, Nogués X. Assessment of early therapy discontinuation and health-related quality of life in breast cancer patients treated with aromatase inhibitors: B-ABLE cohort study. Breast Cancer Res Treat. 2019; 177(1): 53-60. IF 3.471. Q2. • Prieto-Alhambra D, Moral-Cuesta D, Palmer A, Aguado-Maestro I, Bardají MFB, Brañas F, Bueno GA, Caeiro-Rey JR, Cano IA, Barres-Carsi M, Delgado LG, Salomó- Domènech M, Etxebarria-Foronda I, Ferrer BL, Mills S, Herrando LE, Mifsut D, Evangelista LDR, Nogués X, Pérez-Coto I, Blasco JM, Martín-Hernández C, Kessel H, Serra JT, Solis JR, Suau OT, Vaquero-Cervino E, Hernández CP, Mañas LR, Herrera A, Díez-Pérez A. The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study. Arch Osteoporos. 2019; 14(1): 56. IF 2.469. Q2. • Díez-Pérez A, Brandi ML, Al-Daghri N, Branco JC, Bruyère O, Cavalli L, Cooper C, Cortet B, Dawson-Hughes B, Dimai HP, Gonnelli S, Hadji P, Halbout P, Kaufman JM, Kurth A, Locquet M, Maggi S, Matijevic R, Reginster JY, Rizzoli R, Thierry T. Radiofrequency echographic multi-spectrometry for the in-vivo assessment of bone strength: state of the art-outcomes of an expert consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Aging Clin Exp Res. 2019; 31(10): 1375- 1389. IF 2.331. Q3. See all Publications

178 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Musculoskeletal Research

Ongoing Research Projects

• Análisis objetivo mediante geolocalización del perímetro de la marcha en pacientes con estenosis del canal lumbar - Financing institution: Sociedad para el Estudio de las Enfermedades del Raquis (GEER) - Period: from 2018 to 2020 - Principal investigator: Saló Bru, Guillem • Estudio para la mejora de la calidad de vida en mujeres con cáncer de mama tratadas con inhibidores de aromatasa: cohorte B-ABLE - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00818) - Period: from 2017 to 2020 - Principal investigator: Nogués Solan, Francesc Xavier See all Projects

Participation in Research Networks

• CIBER Frailty and Healthy Aging (CIBERFES) - Financing institution: Fondo de Investigación Sanitaria-ISCIII. CIBER (CB16/10/00245) - Period: from 2017 to 2020 - Principal investigator: Nogués Solan, Francesc Xavier • GEnomics of MusculoSkeletal traits TranslatiOnal Network (GEMSTONE) - Financing institution: European COST action CA18139 - Period: from 2019 to 2023 - Principal investigator: Rivadeneira, Fernando • European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) - Financing institution: European working group - Period: from 2019 to 2023 - Principal investigator: Rivadeneira, Fernando

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 179 Inflammatory and Cardiovascular Disorders Musculoskeletal Research

Clinical Trials Signed in 2019

• Estudio de fases I/III integradas, aleatorizado, en doble ciego y multicéntrico, en mujeres posmenopáusicas con osteoporosis, comparativo de la farmacocinética, farmacodinamia, eficacia, seguridad e inmunogenia de GP2411 (producto biológico propuesto similar al denosumab) frente a Prolia® (producto autorizado en la UE) - Protocol: CGP24112301 - Sponsor: HEXAL - Budget: 88,425.6 € - Principal investigator: Nogués Solan, Francesc Xavier • Prospective study for the detection of patients with X-Linked Hypophosphatemia (XLH) and other FGF23-mediated Hypophosphatemic genetic disorders in ambulatory care and Hospital outpatient clinic settings: The Barcelona Hypophosphatemia Study - Sponsor: Kyowa Kirin Farmaceutica SLU - Budget: 84,200 € - Principal investigator: Nogués Solan, Francesc Xavier

Theses

• Lerma E. Estudio del impacto de la infección por VIH en el metabolismo óseo. Universitat Autònoma de Barcelona - Directors: Díez Pérez, Adolf; Knobel H. - Date of defense: 03/06/2019 • Taymouri F. Reference data for bone material strength index (BMSI) measured by impact microindentation. Universitat Autònoma de Barcelona - Directors: Díez Pérez, Adolf; Nogués Solan, Francesc Xavier - Date of defense: 08/02/2019

Appointments

• Francesc Xavier Nogués Solan. Director of the Inflammatory and Cardiovascular Disorders Programme. IMIM. 28/05/2019.

Outreach

Conferences, Seminars and Courses

• Xavier Nogués, Adolfo Díez Pérez, Diana Ovejero. Impact microindentation training seminars. IMIM; November 2019.

180 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Musculoskeletal Research

• Xavier Nogués. Metástasis óseas de tumores sólidos. Fisiopatología de las metástasis óseas. Hospital del Mar, 12-13 September 2019. • Xavier Nogués; Natalia Garcia Giralt. Organizing committee. SEIOMM Congress. Girona, 17-19 October 2019.

Dissemination to Society and Initiatives of Citizen Participation

• Natalia Garcia Giralt, Xavier Nogués. Guided visit to IMIM for high school students from Institut Lluís Peguera. 5 February 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 181 Myogenesis, Inflammation & Muscle Function

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Joaquim Gea Guiral Pilar Ausín Herrero (Researcher) [email protected] Carme Casadevall Fusté (Researcher) Antoni Ferrer Monreal (Researcher) Juana María Martínez Llorens (Researcher) Sergi Pascual Guardia (Researcher) Diego Agustín Rodríguez Chiaradia (Researcher) Ana Balañá Corberó (PhD Student) Eva Balcells Vilarnau (PhD Student) Roberto Chalela Rengifo (PhD Student) Mireia Admetlló Papiol (Technician) Lucilla Piccari (Technician)

Our ongoing research is focused on the role played by proinflammatory cytokines as a signaling molecules in the repairing-remodeling processes in muscles of patients with different processes with a relevant systemic inflammatory component, which share muscle dysfunction and/or loss of muscle mass. The strategic outcome is to identify potential molecular targets of therapies against muscle dysfunction and muscle cachexia. Our research is mainly addressed to lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) and lung cancer, but also muscle problems in aging, fibromyalgia and scoliosis and includes clinical assessment, in vivo and in vitro physiological studies, and molecular biology procedures.

182 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Myogenesis, Inflammation & Muscle Function

More recently, we have initiated a line for the identification of molecular markers of different circumstances present in COPD patients (e.g. gravity, activity, comorbidities, systemic manifestations), using both conventional and ‘omics’ methodologies (transcriptomics, proteomics and metabolomics).

Main Publications

• Marín-Corral J, Dot I, Boguña M, Cecchini L, Zapatero A, Gracia MP, Pascual-Guardia S, Vilà C, Castellví A, Pérez-Terán P, Gea J, Masclans JR. Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation. Intensive Care Med 2019; 45(4): 488-500. IF 18.967. D1. • Chalela R, Bellosillo B, Curull V, Longarón R, Pascual-Guardia S, Badenes-Bonet D, Arriola E, Sánchez-Font A, Pijuan L, Gea J. EGFR and KRAS Mutations in the Non- Tumoral Lung. Prognosis in Patients with Adenocarcinoma. J Clin Med 2019; 8(4): 529. IF 5.688. D1. • Gea J, Pascual S, Castro-Acosta A, Hernández-Carcereny C, Castelo R, Márquez- Martín E, Montón C, Palou A, Faner R, Furlong LI, Seijo L, Sanz F, Torà M, Vilaplana C, Casadevall C, López-Campos JL, Monsó E, Peces-Barba G, Cosío BG, Agustí A; on behalf of the group BIOMEPOC. The BIOMEPOC Project: Personalized Biomarkers and Clinical Profiles in Chronic Obstructive Pulmonary Disease. Arch Bronconeumol 2019; 55(2): 93-99. IF 4.214. Q1. • Barreiro E, Salazar-Degracia A, Sancho-Muñoz A, Aguiló R, Rodríguez-Fuster A, Gea J. Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease. J Appl Physiol 2019; 126(6): 1572-1586. IF 3.140. Q1. • Barreiro E, Sancho-Muñoz A, Puig-Vilanova E, Salazar-Degracia A, Pascual-Guardia S, Casadevall C, Gea J. Differences in micro-RNA expression profile between vastus lateralis samples and myotubes in COPD cachexia. J Appl Physiol 2019 F; 126(2): 403-412. IF 3.140. Q1. See all Publications

Ongoing Research Projects

• Biomarcadores y perfiles clínicos personalizados en la Enfermedad Pulmonar Obstructiva Crónica - Financing institution: Ministerio de Economía y Competitividad. Instituto de Salud Carlos III (SAF2014-54371-R) - Period: from 2015 to 2019 - Principal investigator: Gea Guiral, Joaquim

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 183 Inflammatory and Cardiovascular Disorders Myogenesis, Inflammation & Muscle Function

• Deficiencia de hierro en pacientes con EPOC: Impacto de la reposición con hierro. FACE study (Ferinject Assessment in patients with COPD and iron deficiency to improve Exercise tolerance) - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00649) - Period: from 2018 to 2020 - Principal investigator: Rodríguez Chiaradia, Diego Agustín See all Projects

Participation in Research Networks

• CIBER in Respiratory Diseases (CIBERES). Stable funding from the Spanish network of excellence in respiratory diseases - Financing institution: Instituto de Salud Carlos III (CB06 / 06/0043) - Period: from 2016 to 2019 • MERMAIDS (Platform foR European Preparedness Against (Re)emerging Epidemics, PREPARE) - Financing institution: European Commission. Oxford University (coordinating center). Ref: 2014-602525. - Period: from 2017 to 2022

Clinical Trials Signed in 2019

• Impacto de un programa de asistencia al paciente (PAP) en la persistencia al tratamiento con pirfenidona en pacientes con fibrosis pulmonar idiopática - Register: ML40261 - Principal investigator: Balcells Vilarnau, Eva

Appointments

• Joaquim Gea Guiral. President of the Comité de Grados Universitarios of the Sociedad Española de Neumología y Cirugía Torácica (SEPAR) • Joaquim Gea Guiral. President of the Barcelona Respiratory Network Foundation • Joaquim Gea Guiral. Member of the Advisory Board GlaxoSmithKline • Joaquim Gea Guiral. Member of the Advisory Board AstraZeneca • Joaquim Gea Guiral. Member of the Advisory Board Boehringer Ingelheim • Joaquim Gea Guiral. Member of the Working Group to prepare the ERS statement on respiratory muscle testing at rest and during exercises of the European Respiratory Society (ERS)

184 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Myogenesis, Inflammation & Muscle Function

• Joaquim Gea Guiral. Member of the Management Council of the European Board for Accreditation on Pneumology (EBAP) • Joaquim Gea Guiral. Member of the Working Group for the improvement of the degree studies in Medicine of the Consell Interuniversitari de Catalunya (CIC), Generalitat de Catalunya • Joaquim Gea Guiral. Member of the Working Group for the New Studies Plan of the Universitat Pompeu Fabra Medicine degree (PSMAR-UPF).

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Visit to the Laboratory of the Research Group of Myogenesis, Inflammation & Muscle Function. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019. • Juana María Martínez Llorens. Atenció Multidisciplinària a l’ELA. IV Jornada sobre ELA per a pacients, familiars i cuidadors. 3 May 2019. • Anna Balañá. Workshop Maneig de secrecions respiratòries. IV Jornada sobre ELA per a pacients, familiars i cuidadors. 3 May 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 185 Neuroimmunology

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Jose Enrique Martínez Rodríguez

[email protected] Members

Elvira Munteis Olivas (Researcher) Mireia Llop Trujillano (Technician) Antia Moreira Villanueva (Technician) Andrea Vera Barrón (Technician)

The Neuroimmunology Group was created in 2018 after initially being developed within the IMIM’s Immunity and Infection group. The group studies alterations of the immune system in neurological diseases using a translational approach centered on the patient’s clinical features. The Neuroimmunology Group is particularly interested in multiple sclerosis (MS) as a paradigmatic illness within the autoimmune pathologies of the central nervous system. The group’s current areas of research focus on the following: • The study of chronic herpes virus infections in MS (Epstein-Barr virus, Cytomegalovirus) and their imprint on the Natural Killer (NK) cell compartment, evaluating the potential development of biomarker predictors of activity and progression.

186 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Neuroimmunology

• The immunophenotypic and functional analysis of adaptive NK cell populations and their role in the immunopathology of MS. • Phenotypic and functional study of subpopulations of T and B lymphocytes in the peripheral blood of MS patients, evaluating their relationship with clinical characteristics and treatments that modify the clinical course of the disease. • The immunology of neuromuscular disorders, with special interest in patients with myasthenia gravis. The group currently receives funding from the Spanish Ministry of Science and Innovation (ISCIII Health Research Fund), and is part of the Spanish Network of Multiple Sclerosis (REEM). In addition, the Neuroimmunology Group has extensive experience in implementing phase II and III clinical trials using diverse immunomodulatory therapies on MS patients. The team comprises a principal investigator, three clinical researchers, and an advanced clinical practice nurse, who coordinates the clinical trials.

Main Publications

• Ois A, Vivas E, Figueras-Aguirre G, Guimaraens L, Cuadrado-Godia E, Avellaneda C, Bertran-Recasens B, Rodríguez-Campello A, Gracia MP, Villalba G, Saldaña J, Capellades J, Fernández-Candil JL, Roquer J. Misdiagnosis Worsens Prognosis in Subarachnoid Hemorrhage with Good Hunt and Hess Score. Stroke 2019; 50(11): 3072-3076. IF: 6.046. D1. • Moreira A, Alari-Pahissa E, Munteis E, Vera A, Zabalza A, Llop M, Villarrubia N, Costa- García M, Álvarez-Lafuente R, Villar LM, López-Botet M, Martínez-Rodríguez JE. Adaptive features of natural killer cells in multiple sclerosis. Front Immunol 2019; 10: 2403. IF 4.716. Q2. See all Publications

Ongoing Research Projects

• Respuesta adaptativa mediada por células Natural Killer en la esclerosis múltiple - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00254) - Period: from 2018 to 2020 - Principal investigator: Martínez Rodríguez, José Enrique See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 187 Inflammatory and Cardiovascular Disorders Neuroimmunology

Participation in Research Networks

• Red Española de Esclerosis Múltiple - Financing institutions: Instituto de Salud Carlos III, European Regional Development Fund (Grant RD16/0015/0011) the Ministerio de Economía y Competitividad - Principal investigator: López-Botet, Miguel

Clinical Trials Signed in 2019

• A phase III, multi-centre, randomised, double-blind, placebo-controlled, parallel-group clinical trial to investigate the efficacy and safety of BX-1 for the symptomatic relief of spasticity in patients with multiple sclerosis - Protocol: DroSpas-1 - Sponsor: BIONORICA - Budget: 36,500 € - Principal investigator: Martínez Rodríguez, José Enrique • Estudio observacional transversal con recogida de datos retrospectivos para valorar el impacto económico de la Esclerosis Múltiple Secundaria Progresiva - Protocol: CBAF312AES01 / NOV-EMS-2019-01 - Sponsor: Novartis Farmacéutica, S.A. - Budget: 2,925 € - Principal investigator: Martínez Rodríguez, José Enrique

Outreach

Conferences, Seminars and Courses

• José Enrique Martínez Rodríguez. VII Jornada d’Actualització del Tractament i Diagnòstic de les Malaties Neurològiques més Prevalents: Esclerosi Múltiple. Societat Catalana de Neurologia. Mataró, November 2019.

188 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurovascular

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Jaume Roquer González Carla Avellaneda Gómez (Researcher) [email protected] Elisa Cuadrado Godia (Researcher) Eva Giralt Steinhauer (Researcher) Jordi Jiménez Conde (Researcher) Ángel Javier Ois Santiago (Researcher) Ana María Rodríguez Campello (Researcher) Carolina Soriano Tárraga (Researcher) Eva Langa Muñoz (Technician) Uxue Lazcano Dobao (Technician) Irene Navalpotro Gómez (Technician) Gemma Romeral Ballester (Technician) Miguel Ángel Rubio Pérez (Technician) Rosa Maria Vivanco Hidalgo (Technician)

This is a clinical group involved in stroke research. Currently our group is included in the Red de Enfermedades Vasculares Cerebrales (INVICTUS PLUS) that is one of the main Spanish research networks. The strengths of our group are: first, our ongoing database named BASICMAR, that contains extensive demographic, epidemiological, clinical, and outcome data about all stroke patients (n=8,300) admitted to our hospital, and second, our large collection of blood sample of stroke patients for genetic and biomarkers studies (n=6,000). The two main research lines are:

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 189 Inflammatory and Cardiovascular Disorders Neurovascular

1. Clinical research and biomarkers in stroke: epidemiology, natural history and vascular risk factors, stroke biomarkers, environmental and stroke, diet and stroke, neurosonology and neuro-imaging. 2. Genetic and stroke research: our unit is part of the International Stroke Genetics Consortium, which includes many international (USA, Europe) and national groups and of the GENESTROKE Consortium working to develop GWAS and EWAS studies and projects.

Main Publications

• Mola-Caminal M, Carrera C, Soriano-Tárraga C, Giralt-Steinhauer E, Díaz-Navarro RM, Tur S, Jiménez C, Medina-Dols A, Cullell N, Torres-Aguila NP, et al. PATJ low frequency variants are associated with worse ischemic stroke functional outcome: a genome- wide meta-analysis. Circulation Res 2019; 124: 114-120. IF 15.862. Q1. • Marini S, Crawford K, Morotti A, Lee MJ, Pezzini A, Moomaw CJ, Flaherty ML, Montaner J, Roquer J, Jiménez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado- Godia E, Soriano-Tarraga C, et al; International Stroke Genetics Consortium. Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/ Ethnicity: A Meta-analysis. JAMA Neurol 2019; 76: 480-491. IF 12.321. D1. • Roquer J, Vivanco-Hidalgo RM, Prats-Sánchez LL, Martínez-Domeño A, Guisado- Alonso D, Cuadrado-Godia E, Giralt Steinhauer E, Jiménez-Conde J, Rodríguez- Campello A, Martí-Fàbregas J, Ois A. Interaction of atrial fibrillation and antithrombotics on outcome in intracerebral hemorrhage. Neurology 2019; 93: e1820-e1829. IF 8.689. D1. • Ois A, Vivas E, Figueras-Aguirre G, Guimaraens L, Cuadrado-Godia E, Avellaneda C, Bertran-Recasens B, Rodríguez-Campello A, Gracia MP, Villalba G, Saldaña J, Capellades J, Fernández-Candil JL, Roquer J. Misdiagnosis worsens prognosis in subarachnoid hemorrhage with good Hunt & Hess score. Stroke 2019; 50: 3072- 3076. IF 6.058. D1. • Vivanco-Hidalgo RM, Avellaneda-Gómez C, Dadvand P, Cirach M, Ois A, Gómez- González A, Rodríguez-Campello A, de Ceballos P, Basagaña X, Zabalza A, Sunyer J, Cuadrado-Godia E, Roquer J, Wellenius GA. Association of residential air pollution, noise, and greenspace with initial ischemic stroke severity. Environ Res 2019; 179 (PtA): 108725. IF 5.026. D1. See all Publications

190 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Neurovascular

Ongoing Research Projects

• Evaluación a nivel poblacional del impacto de la contaminación atmosférica sobre la incidencia y pronóstico del ictus isquémico - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00056) - Period: from 2019 to 2021 - Principal investigator: Roquer González, Jaume; Vivanco Hidalgo, Rosa M. • Contribución de la epigenética en el pronóstico del ictus. Estudio de EWAS y Micro- RNAs circulantes - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI18/00022) - Period: from 2019 to 2021 - Principal investigator: Jiménez Conde, Jordi; Rodríguez Campello, Ana. • The Chemical Optimization of Cerebral Embolectomy (CHOICE) Trial - Financing institution: Fundació La Marató de TV3 (20170732) - Period: from 2018 to 2021 - Principal investigator: Cuadrado Godia, Elisa See all Projects

Participation in Research Networks

• Red de Enfermedades Vasculares Cerebrales. INVICTUS PLUS. - Financing institution: Fondo de Investigación Sanitaria-ISCIII. Subprograma RETICS (RD16/0019/0002) - Period: from 2016 to 2021 - Principal investigator: Roquer González, Jaume

Clinical Trials Signed in 2019

• Estudio internacional de fase 2, aleatorizado, doble ciego, controlado con placebo, de búsqueda de dosis adaptada a la respuesta, de BMS-986177, un inhibidor del factor XIa oral, para la prevención de los nuevos casos de ictus isquémico o de infarto cerebral silente en pacientes tratados con Aspirina y clopidogrel después de un ictus no hemorrágico agudo o un accidente isquémico transitorio (AIT) - Protocol: CV010-031 - Sponsor: Bristol-Myers Squibb International Corporation (BMSIC) - Budget: 144,000 € - Principal investigator: Rodríguez Campello, Ana María

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 191 Inflammatory and Cardiovascular Disorders Neurovascular

• Registro nacional de hemorragias intracerebrales (ARICH) en relación al tratamiento anticoagulante - Protocol: VHI-PRO-2019-01 - Sponsor: Fundació Institut Recerca Hospital Vall d’Hebron - Budget: No economic compensation - Principal investigator: Rodríguez Campello, Ana María

Awards

• Jaume Roquer. TOP 20 award 2019 “Área de Sistema Nervioso”. Best neurological department 2019 in Spain. 20th Edition Hospitales TOP 20. Madrid, 18/12/19. • European Certification by the European Stroke Organization. Hospital del Mar Stroke Center ESO. 11/12/19. First stroke center accredited in Spain.

Appointments

• Ana Rodríguez Campello. Secretary of the Stroke Group of the Societat Catalana de Neurologia. • Ana Rodríguez Campello. National auditor of the European Stroke Organisation for acreditation of stroke units and stroke centers.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Ana Rodríguez Campello. Ictus. Escola de Salut de la Barceloneta. Casal Gent Gran de la Barceloneta. Barcelona, 13 February 2019.

192 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Rehabilitation

> Inflammatory and Cardiovascular Disorders RESEARCH GROUP

Group Leader Members Esther Duarte Oller Roser Belmonte Martínez (Researcher) [email protected] Maria Coll Molinos (Researcher) Ferran Escalada Recto (Researcher) Anna Guillén Solà (Researcher) Ester Marco Navarro (Researcher) Josep Maria Muniesa Portoles (Researcher) Mercè Piqueras Céspedes (Researcher) Marta Tejero Sánchez (Researcher) Monique Messaggi Sartor (Technician)

The main research areas of the group are: • Neurological rehabilitation: brain plasticity and motor recovery by developing new technologies as Virtual Reality and Music Supported Therapy in stroke patients. • Sarcopenia and malnutrition: ultrasound assessment, exercise and nutritional interventions. • Effects of physical training and exercise on cardiovascular disease, chronic respiratory disease, cancer and ageing – Prehabilitation programs. • Dysphagia: assessment and therapeutic strategies. • Development of telerehabilitation systems applied to neurological, pulmonary and cardiorespiratory diseases.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 193 Inflammatory and Cardiovascular Disorders Rehabilitation

The group’s purpose is to enhance the interaction between basic and clinical sciences, and health services, with potential translational application, providing innovative and potentially effective treatment alternatives.

Main Publications

• Marco E, Sánchez-Rodríguez D, Dávalos-Yerovi NV, Duran X, Pascual EM, Muniesa JM, Rodríguez DA, Aguilera-Zubizarreta A, Escalada F, Duarte E. Malnutrition according to ESPEN consensus predicts hospitalizations and long-term mortality in rehabilitation patients with stable chronic obstructive pulmonary disease. Clinical Nutrition 2019; 38(5): 2180-2186. IF 6.402. Q1. • Sánchez-Rodríguez D, Marco E, Schott AM, Rolland Y, Blain H, Vázquez-Ibar O, Escalada F, Duran X, Muniesa JM, Annweiler C. Malnutrition according to ESPEN definition predicts long-term mortality in general older population: findings from the EPIDOS study-Toulouse cohort. Clinical Nutrition 2019; 38(6): 2652-2658. IF 6.402. Q1. • Dávalos-Yerovi V, Marco E, Sánchez-Rodríguez D, Guillen-Solà A, Duran X, Pascual EM, Muniesa JM, Escalada F, Duarte E. Sarcopenia according to the revised European consensus on definition and diagnosis (EWGSOP2) criteria predicts hospitalizations and long-term mortality in rehabilitation patients with stable chronic obstructive pulmonary disease. Journal of the American Medical Directors Association 2019; 20(8): 1047-1049. IF 4.899. Q1. • Sánchez-Rodríguez D, Hope S, Piotrowicz K, Benoit F, Czesak J, Dallmeier D, Decker G, De Spiegeleer A, Højmann AH, Hrnciarikova D, Marco E, Mendes D, Meza D, Nascimento P, Rodrigues A, Surquin M, Toscano-Rico M, Vankova H, Vetrano DL, Gasowski J, Van Den Noortgate N, Landi F. Sarcopenia in Acute Care Patients: Protocol for the European Collaboration of Geriatric Surveys: Sarcopenia 9+ EAMA Project. J Am Med Dir Assoc 2019; 20(11): e1-e3. IF 4.899. Q1. • Pujol-Blaya V, Salinas-Huertas S, Catasús ML, Pascual T, Belmonte R. Effectiveness of a precast adjustable compression system compared to multilayered compression bandages in the treatment of breast cancer-related lymphoedema: a randomized, single-blind clinical trial. Clinical Rehabilitation 2019; 33(4): 631-641. IF 2.738. Q1. See all Publications

Ongoing Research Projects

• The RETORNUS-2 Study: Impact of respiratory muscle training on swallowing in stroke patients with dysphagia - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/01081) - Period: from 2017 to 2019 - Principal investigator: Guillén Solà, Anna

194 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Inflammatory and Cardiovascular Disorders Rehabilitation

• Brain Connects: Brain connectivity during stroke recovery and rehabilitation - Financing institution: Fundació La Marató de TV3 - Period: from 2018 to 2020 - Principal Investigator: Duarte Oller, Esther See all Projects

Participation in Research Networks

• The activity of the Rehabilitation Research Group (RERG) is carried out in collaboration with other IMIM research groups belonging to the Inflammatory and Cardiovascular Disorders Programme. We have also established collaborative projects with other international institutions, highlighting: SPECS-Pompeu Fabra University (Barcelona); Heinrich-Heine-Universität (Düsseldorf, Germany); Guger Technologies OEG (Austria); Tyromotion GMBH (Austria); Private ICT and Health Foundation (Mataró); Hospital Joan XXIII (Tarragona); Cognition and Brain Plasticity Group of the Biomedical Research Institute of Bellvitge (Barcelona), and Research Institute Hospital Vall d’Hebron (Barcelona). The RERG also participates in collaborative projects with Liège University (Liège, Belgium), Vrije Universiteit (Brussels, Belgium), Antwerp University (Antwerp, Belgium), European Centre for Disease Prevention and Control (ECDC), Centro Nacional de Epidemiología de España of the Instituto de Salud Carlos III (Madrid, Spain), and Cardiovascular Foundation of Colombia (Santander, Colombia).

Theses

• Grau Sánchez, Jennifer. Music-supported Therapy in the rehabilitation of motor deficits after stroke. Universitat de Barcelona - Directors: Duarte Oller, Esther; Rodríguez-Fornells, Antoni - Date of defense: 11/01/2019

Awards

• Ester Marco. Best presentation award of the Catalan Society of Physical Medicine and Reahabilitation (SCMFiR) 2019. Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de Balears. March 2019. • Ester Marco Navarro. SORECAR Award for the best communication on cardiorespiratory rehabilitation. Sponsored by SANRO. 57th National Congress. Sociedad Española de Rehabilitación y Medicina Física. May 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 195 Inflammatory and Cardiovascular Disorders Rehabilitation

Appointments

• Esther Duarte. Head of the Department of Physical Medicine and Rehabilitation. Parc de Salut Mar. January 2019. • Anna Guillén-Solà. Secretary of the Director Board, Catalan Society of Rehabiliation and Physical Medicine. June 2019. • Ester Marco. Accreditation of Research by the Agència per la Qualitat del Sistema Universitari de Catalunya (AQU). June 2019.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Esther Duarte. Fundació Ictus. Participation in advising people who have suffered a stroke and in the evaluation of projects to promote research on this disease.

196 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY > SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 197 Programmes

Neurosciences

13 152 53 135 Research Professionals Research Publications groups projects

Programme Director Rafael de la Torre

RESEARCH GROUPS Perioperative Medicine and Pain Lluís Gallart Addiction Marta Torrens ASSOCIATED GROUPS Anxiety, Affective Disorders and Schizophrenia Antoni Bulbena Behavioral Neurobiology Olga Valverde Doping Control Research Group Rosa Ventura Genetics Luis Alberto Pérez Jurado Epilepsy Rodrigo Alberto Rocamora Laboratory of Neuropharmacology Rafael Maldonado Integrative Pharmacology and Systems Neuroscience Neuroimaging of Mental Disorders Rafael de la Torre Òscar Vilarroya

Mental Health Physiology of Cognition and Alzheimer’s Víctor Pérez and Francesc Colom Prevention José Luis Molinuevo Neurofunctionality and Brain Language Jordi Peña Casanova

198 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Programme

The mission of the Neurosciences Research Programme (NRP) is to support clinical research, which ultimately should give us a better understanding of mental and neurodegenerative diseases. The Programme is formed by 13 research groups with a clinical orientation.

Outstanding scientific achievements

During 2019, NRP coordinated an Alzheimer Association (PENSA) project and participated as partner in several H2020 research projects: GO-DS21, MINDUP and other international projects funded by the University of Maastricht, Jérôme Lejeune Foundation, NEURON-ERANET and JPND.

Some scientific publications

• Olesti E, Farré M, Carbó ML, Papaseit E, Perez-Mañá C, Torrens M, Yubero-Lahoz S, Pujadas M, Pozo ÓJ, de la Torre R. Dose-Response Pharmacological Study of Mephedrone and Its Metabolites: Pharmacokinetics, Serotoninergic Effects, and Impact of CYP2D6 Genetic Variation. Clin Pharmacol Ther. 2019 Sep; 106(3): 596- 604. • Rodríguez-Morató J, Goday A, Langohr K, Pujadas M, Civit E, Pérez-Mañá C, Papaseit E, Ramon JM, Benaiges D, Castañer O, Farré M, de la Torre R. Short- and medium- term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity. Sci Rep. 2019 Dec 31; 9(1): 20405. • Ramon-Duaso C, Gener T, Consegal M, Fernández-Avilés C, Gallego JJ, Castarlenas L, Swanson MS, de la Torre R, Maldonado R, Puig MV, Robledo P. Methylphenidate Attenuates the Cognitive and Mood Alterations Observed in Mbnl2 Knockout Mice and Reduces Microglia Overexpression. Cereb Cortex. 2019 Jul 5; 29(7): 2978-2997. • Boronat A, Mateus J, Soldevila-Domenech N, Guerra M, Rodríguez-Morató J, Varon C, Muñoz D, Barbosa F, Morales JC, Gaedigk A, Langohr K, Covas MI, Pérez-Mañá C, Fitó M, Tyndale RF, de la Torre R. Cardiovascular benefits of tyrosol and its endogenous conversion into hydroxytyrosol in humans. A randomized, controlled trial. Free Radic Biol Med. 2019 Nov 1; 143: 471-481. • Olesti E, De Toma I, Ramaekers JG, Brunt TM, Carbó ML, Fernández-Avilés C, Robledo P, Farré M, Dierssen M, Pozo ÓJ, de la Torre R. Metabolomics predicts the pharmacological profile of new psychoactive substances. J Psychopharmacol. 2019 Mar; 33(3): 347-354. • Navarro-Romero A, Vázquez-Oliver A, Gomis-González M, Garzón-Montesinos C, Falcón-Moya R, Pastor A, Martín-García E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodríguez-Moreno A, Maldonado R, Ozaita A. Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome. Neurobiol Dis. 2019; 125: 92-106.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 199 Addiction

> Neurosciences RESEARCH GROUP

Group Leader Members Marta Torrens Mèlich Mònica Astals Vizcaíno (Researcher) [email protected] Claudio Guillermo Castillo Buenaventura (Researcher) Maria Francina Fonseca Casals (Researcher) Ana Martín Sánchez (Researcher) Juan Ignacio Mestre Pintó (Researcher) María Robles Martínez (Researcher) Gabriel Vallecillo Sánchez (Researcher) Gerard Mateu Codina (PhD Student) María Alías Ferri (Technician) Fernando Nicolás Dinamarca Cáceres (Technician) Alonso Pérez Toribio (Technician)

This is a multidisciplinary team of health professionals (psychiatrists, psychologists, internist, nurses…) that share clinical, research and teaching activities. In the research area, the main aim is to study addiction to substances from different perspectives to improve secondary prevention and treatment. The main lines of research are: 1) Clinical and therapeutic aspects of substance use disorders (opiates, cocaine, alcohol, cannabis…). 2) Psychiatric and somatic (i.e. HIV, HCV) comorbidity in substance use disorders (diagnostic tools, neurobiology, factors associated, treatment…).

200 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Addiction

3) New psychoactive substances of abuse (detection of abuse, potential neurotoxicity). 4) Gender perspective of addictions.

Main Publications

• Farrell M, Martín NK, Stockings E, Bórquez A, Cepeda JA, Degenhardt L, Ali R, Tran LT, Rehm J, Torrens M, Shoptaw S, McKetin R. Responding to global stimulant use: challenges and opportunities. Lancet 2019; 394(10209): 1652-1667. IF 59.102. Q1. • Martínez R, Pérez-Mañá C, Papaseit E, Fonseca F, de la Torre R, Pizarro N, Torrens M, Farré M. Soy Isoflavone Extract Does Not Increase the Intoxicating Effects of Acute Alcohol Ingestion in Human Volunteers. Front Pharmacol 2019; 10: 131. IF 3.845. Q1. • García-Marchena N, Barrera M, Mestre J, Araos P, Serrano A, Pérez-Mañá C, Papaseit E, Fonseca F, Ruiz JJ, Rodríguez de Fonseca F, Farré M, Pavón FJ, Torrens M. Inflammatory mediators and dual depression: Potential biomarkers in plasma of primary and substance-induced major depression in cocaine and alcohol use disorders. PLoS ONE 2019; 14(3): e0213791. IF 2.776. Q2. • Robles-Martínez M, García-Carretero MÁ, Gibert Rahola, Rodríguez-Cintas L, Palma- Álvarez RF, Abad AC, Sorribes M, Torrens M, Roncero C. Relación entre craving e impulsividad en pacientes con dependencia alcohólica con o sin patología dual en tratamiento ambulatorio: un estudio descriptivo. Actas Esp Psiquiatr 2019; 47(3): 88- 96.IF 1.479. Q4. See all Publications

Ongoing Research Projects

• Analysis, Knowledge dissemination Justice implementation and Special Testing of Novel Synthetic Opioids - Financing institution: European Commission (806996-JUSTSO-JUST-2017-AG- DRUG) - Period: from 2018 to 2020 - Principal investigator: Torrens Mèlich, Marta • Evaluación de una herramienta e-health para la reducción del consumo de cannabis - Financing institution: Ministerio de Sanidad, Consumo y Bienestar Social / Plan Nacional Sobre Drogas (2019I010) - Period: from 2019 to 2022 - Principal investigator: Torrens Mèlich, Marta

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 201 Neurosciences Addiction

• Biomarcadores de la Depresión Inducida: BIODEP - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00603) - Period: from 2016 to 2022 - Principal investigator: Torrens Mèlich, Marta See all Projects

Participation in Research Networks

• Red de Trastornos Adictivos - Financing institution: Fondo de Investigación Sanitaria. Subprograma RETICS RD16/0017/0010 - Period: from 2016 to 2021 - Principal investigator: Torrens Mèlich, Marta • International Network on Hepatitis in Substance Users (INSHU) - Financing institution: INSHU - Period: from 2018 to 2020 - Principal investigator: Torrens Mèlich, Marta • Informal Scientific Network of the UNO Drugs and Crime and WHO - Financing institution: UNODC - Period: from 2015 to 2020 - Principal investigator: Torrens Mèlich, Marta

Theses

• Mateu G. Factores genéticos en patología dual. Universitat Autònoma de Barcelona - Directors: Torrens Mèlich, Marta; Fonseca Casals, Maria Francina - Date of defense: 08/05/2019 • Martínez Riera R. Uso terapéutico de las isoflavonas de la soja en el trastorno por consumo de cocaína. Universitat Autònoma de Barcelona - Directors: Torrens Mèlich, Marta; Fonseca Casals, Maria Francina; Farré, M. - Date of defense: 30/10/2019 • Mateus J. Biomarcadores de alcohol y su relación con la dosis. Universitat Autònoma de Barcelona - Directors: Fonseca Casals, Maria Francina; Farré, M; Pérez-Mañá, C. - Date of defense: 10/12/2019

202 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Addiction

Appointments

• Marta Torrens. Member of the Consell Assessor de Salut Mental i Addiccions. Departament de Salut, Generalitat de Catalunya. 05/06/2019. • Marta Torrens. Member of the Scientific Committee of the European Monitoring Center for Drugs and Drug Addiction (EMCDDA). 13/12/2019.

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Marta Torrens. Perspectiva de gènere en neurociència: si no ho fem les dones, qui ho farà? Dones en Neurociència-11 de febrer: Dia Internacional de la Dona i la Xiqueta en la Ciència. Comité de Mujer y Neurociencia de la Sociedad Española de Neurociencia (SENC). Universitat de València, 11 February 2019. • Marta Torrens. Addicció a drogues: nous temps, vells problemes? Diàleg Humanístic UPF, Barcelona, 12 February 2019. • Marta Torrens. Consumo de sustancias y patología dual. Jornada sobre nuevas claves para la prevención del consumo de sustancias entre los y las jóvenes desde la perspectiva comunitaria. Conferencias de la Facultad de Arquitectura de Donostia. Jornadas Deportivas. Mondragón, 7 June 2019. • Marta Torrens. Addiccions. La Salut Mental i les sèries de TV: tractament i estigma. Unitat de Dinamització, Facultat de Psicologia and Comunitat de Recerca Estratègica en Salut Mental. Universitat Autònoma de Barcelona. Bellaterra, 15 July 2019. • Marta Torrens. Ús terapèutic dels psicodislèptics: Pros i contres. Nous reptes en Salut Mental i Addiccions, 7th edition. Barcelona 13 November 2019. • Francina Fonseca. Noves drogues: velles substàncies perilloses. Science Festival 2019 Barcelona, 27 October 2019. • Francina Fonseca. Round table: L’alcohol, problema de tothom. Escola de la Salut de la Barceloneta. Barcelona, 22 May 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 203 Anxiety, Affective Disorders and Schizophrenia

> Neurosciences RESEARCH GROUP

Group Leader Members Antonio Bulbena Vilarrassa Anna Mané Santacana (Researcher) [email protected] Luis Miguel Martín López (Researcher) Guillem Pailhez Vidual (Researcher) Purificación Salgado Serrano (Researcher) María José Tribó Boixareu (Researcher) Esperanza González Fernández (Research Assistant)

The group is made up of different researchers involved in clinical work either in hospital or primary care. Although the backbone of the group is the original description (and derivative) of the association between anxiety and Joint Hypermobility Syndrome (JHS), current lines of research include bipolar illness, schizophrenia, first-episode psychosis, cognitive psychotherapy for anxiety, obsessive compulsive disorder, psychiatric emergency services, Hikikomori syndrome and also the expert patient. A very active group in ethological research also joined the group and has done pioneering research on the Noah Syndrome (animal hoarding), but is also remaining active on areas such as pet grief, human-animal interaction, etc. The research group was recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a consolidated research group 2017-2020 (SGR 52; Principal investigator: Antonio Bulbena Vilarrasa).

204 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Anxiety, Affective Disorders and Schizophrenia

Main Publications

• Ahmed AO, Kirkpatrick B, Galderisi S, Mucci A, Rossi A, Bertolino A, Rocca P, Maj M, Kaiser S, Bischof M, Hartmann-Riemer MN, Kirschner M, Schneider K, García-Portilla MP, Mané A, Bernardo M, Fernández-Egea E, Jiefeng C, Jing Y, Shuping T, Gold JM, Allen DN, Strauss GP. Cross-cultural Validation of the 5-Factor Structure of Negative Symptoms in Schizophrenia. Schizophrenia Bull 2019; 45(2): 305-314. IF 7.289. Q1. • Bowen J, Fatjó J, Serpell JA, Bulbena-Cabré A, Leighton E, Bulbena A. First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog. Sci Rep 2019; 9(1): 8629. IF. 4.011 Q1. • Tribó MJ, Turroja M, Castaño-Vinyals G, Bulbena A, Ros E, García-Martínez P, Tausk F, Sagristà M, Pujol RM, Ferran M, Gallardo F. Patients with Moderate to Severe Psoriasis Associate with Higher Risk of Depression and Anxiety Symptoms: Results of a Multivariate Study of 300 Spanish Individuals with Psoriasis. Acta Derm-Venereol 2019; 99(4): 417-422. IF 3.531. Q1. • Alba L, León-Caballero J, Córcoles D, González-Fresnedo AM, Bellsolà M, Martín LM, Pérez V. Unidad de Hospitalización Domiciliaria del Hospital del Mar. Equipo de atención psiquiátrica domiciliaria en el área de Barcelona. Rev Psiquiatr Salud Ment 2019; 12(4): 207-212. IF 2.927. Q3. • Bulbena-Cabré A, Duñó L, Almeda S, Batlle-Vila S, Camprodon-Rosanas E, Martín LM, Bulbena A. La hiperlaxitud articular como marcador de ansiedad en niños. Rev Psiquiatr Salud Ment 2019; 12(2): 68-76. IF 2.927. Q3. See all Publications

Ongoing Research Projects

• Rehabilitación cognitiva combinada con ejercicio físico en el tratamiento de la esquizofrenia: estudio controlado aleatorizado. - Financing institution: Instituto de Salud Carlos III (PI15/00453) - Period: from 2015 to 2020 - Principal investigator: Mané Santacana, Anna See all Projects

Clinical Trials Signed in 2019

• Phenomics and Genomics of Clozapine Pharmacotherapy - Sponsor: UMC Utrecht - Protocol: ABR 52728.041.15 - Budget: No economic compensation - Principal investigator: Mané Santacana, Anna

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 205 Doping Control Research Group

> Neurosciences RESEARCH GROUP

Group Leader R o s a Ve n t u r a A l e m a n y

[email protected]

Members María Lázaro Miguélez (Technician) Sonia Leal Xalma (Technician) Rosa Leonor Bergés Casas (Researcher) Núria Monfort Mercader (Technician) Élida Alechaga Silva (Technician) Montserrat Núñez Maroto (Technician) María del Rosario Álvarez García (Technician) Sílvia Petit Guiral (Technician) Indira Anselmo Castellano (Technician) Laura Pont Villanueva (Technician) Laura Benítez Gracia (Technician) Jordi Puigdemasa Pérez (Technician) Claudia Bressan (Technician) Rosalía Ramírez Llanelis (Technician) Belén Cano Ávalos (Technician) Lídia Requena Tutusaus (Technician) Sergi Coll Camenforte (Technician) María Pilar Sáez Hernández (Technician) Ignacio Coll García (Technician) Elia Sanjuán Estaún (Tchnician) Albert Contreras Llin (Technician) Alejandro Terrero González (Technician) Susana Cuadras Navarro (Technician) Marta Vicén Morales (Technician) Immaculada Figuera Figuera (Technician) Daria Navarra Alcrudo (Research Assistant) Lorena Garrostas Carreño (Technician) Marta Gómez Gijón (Technician)

206 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Doping Control Research Group

The Doping Control Research Group performs scientific research to contribute to the progress of doping control in sports, with the objective of ensuring doping-free sport and protecting the health of athletes. It is formed of personnel belonging to the Catalan Antidoping Laboratory. The research group was recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a consolidated research group (2017 SGR 81; Principal investigator: Rosa Ventura Alemany). The research focuses on the development and improvement of analytical methods to detect the misuse of doping agents and on the study of new markers to improve the detection of substances and methods prohibited in sport. In addition, the group works on new mass spectrometry techniques for detecting and quantifying drugs and their metabolites, and endogenous metabolites in biological fluids to study pharmacokinetics, metabolism and pharmacodynamics. The team also collaborates with other research groups in determining environmental pollutants in biological samples. The group’s main areas of interest in research are the following: • Metabolism of anabolic androgenic steroids (long-term metabolites). • Detection of the administration of endogenous steroids. • Study of the factors influencing the endogenous steroid profile. • Discrimination of prohibited and permitted uses of glucocorticoids. • Discrimination of prohibited and permitted uses of β2-agonists. • Detection of the use of blood transfusions. • Detection of growth hormone releasing peptides. • Use of dried blood spots in doping control. Moreover, members of the Doping Control Research Group are actively involved in training programs in chemistry and toxicology for graduate and undergraduate students (Pompeu Fabra University, University of Barcelona, Basque Country University). Finally, the Group includes the Catalan Anti-doping Laboratory, one of the 30 accredited laboratories in the world to perform anti-doping tests. The Laboratory obtained the renewal of the following accreditations in 2019: • World Anti-Doping Agency, to perform anti-doping analyses in athletes. • ISO17025, to perform anti-doping and toxicology assays. • Association of Official Racing Chemists, to perform anti-doping analyses in animals.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 207 Neurosciences Doping Control Research Group

Main Publications

• Coll S, Matabosch X, Llorente-Onaindia J, Carbó M, Pérez-Mañá C, Monfort N, Monfort J, Ventura R. Elimination profile of triamcinolone hexacetonide and its metabolites in human urine and plasma after a single intra-articular administration. Drug Test Anal 2019; 11(11-12): 1589-1600. IF 2.799. Q1. • Esquivel A, Alechaga E, Monfort N, Ventura R. Sulfate metabolites improve retrospectivity after oral testosterone administration. Drug Test Anal 2019; 11(3): 392-402. IF 2.799. Q1. • Esquivel A, Alechaga E, Monfort N, Yang S, Xing Y, Moutian W, Ventura R. Evaluation of sulfate metabolites as markers of intramuscular testosterone administration in Caucasian and Asian populations. Drug Test Anal 2019; 11(8): 1218-1230. IF 2.799. Q1. • Coll S, Monfort N, Alechaga E, Matabosch X, Pérez-Mañá C, Ventura R. Additional studies on triamcinolone acetonide use and misuse in sports: Elimination profile after intranasal and high-dose intramuscular administrations. Steroids 2019; 151: 108464. IF 2.136. Q1. See all Publications

Ongoing Research Projects

• Evaluation of alternative glucocorticosteroid metabolites for the discrimination between legal and forbidden administration routes - Financing institution: World Anti-Doping Agency (13D22RV) - Period: from 2014 to 2019 - Principal investigator: Ventura Alemany, Rosa • Improving detection of anabolic steroids: new screening based on the direct analysis of phase II metabolites using LC-Q-HRMS - Financing institution: World Anti-Doping Agency (15A15RV) - Period: from 2016 to 2020 - Principal investigator: Ventura Alemany, Rosa • Studies on intra-articular and peri-articular administrations of glucocorticoids - Financing institution: World Anti-Doping Agency (16C11RV) - Period: from 2017 to 2020 - Principal investigator: Ventura Alemany, Rosa

208 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Doping Control Research Group

• Improving Detection of Endogenous Anabolic Steroids misuse by measuring endogenous Sulfate metabolites (IDEASS) - Financing institution: World Anti-Doping Agency (17D09RV) - Period: From 2018 to 2019 - Principal investigator: Ventura Alemany, Rosa See all Projects

Theses

• Coll S. Studies on glucocorticoids in sports drug testing. Universitat Pompeu Fabra - Director: Ventura Alemany, Rosa - Date of defense: 10/12/2019

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Sergi Coll, Élida Alechaga. Guided tour of the Catalonian Antidoping Laboratory to students of Narcís Monturiol Institute. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 5 April 2019. • Sergi Coll, Élida Alechaga. BioJunior 2019. An Open Day only for students. Guided tours of the Catalonian Antidoping Laboratory to High School students. 3 May 2019. • Élida Alechaga, Laura Pont, Lídia Requena. Guided tours of the Catalonian Antidoping Laboratory. Open Day of the Parc de Recerca Biomèdica de Barcelona (PRBB), 5 October 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 209 Epilepsy

> Neurosciences RESEARCH GROUP

Group Leader Members Rodrigo Alberto Rocamora Gerard Conesa Bertran (Researcher) Zúñiga Alessandro Principe (Researcher) [email protected] Rodrigo Quian Quiroga (Researcher)

The Epilepsy Group is part of the Neurosciences Programme at the IMIM. The research carried out is based on the clinical activity of the Epilepsy Multidisciplinary Unit (UME) at the Hospital del Mar. The main lines of research are: 1. Human cognition and single neuron registers (SNR). 2. Location of focus and crisis prediction. 3. Clinical epileptology and comorbidities. 4. Pharmacotherapy of epilepsy. The Epilepsy Unit is a national reference centre (CSUR) for refractory epilepsies designated by the Ministry of Health and is part of the European Reference Network for epilepsy, EPICare. The EMU has four VEEG monitoring beds equipped with 128/256 channel stereoelectroencephalography (SEEG) acquisition systems. More than 150 VEEGs are performed per year, including 15-18 invasive studies. More than 50 patients with epilepsy are operated each year.

210 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Epilepsy

The EMU has been a pioneer in epilepsy surgery in Spain and has marked its development: 1) It introduced robotic surgery in epilepsy. 2) It implemented SEEG in the country. 3) It began laser surgery in epilepsy. 4) It is the only centre that uses single neuron recording. In teaching, the UME has been training national and international specialists in epilepsy for six years through an annual fellowship. The Head of the Unit is also an associate professor of bioengineering at UPF and a course coordinator. The UME directs UPF Theses for Engineering Degrees and PhDs in Biomedicine.

Main Publications

• Pacheco Estefan D, Sánchez-Fibla M, Duff A, Principe A, Rocamora R, Zhang H, Axmacher N, Verschure PFMJ. Coordinated representational reinstatement in the human hippocampus and lateral temporal cortex during episodic memory retrieval. Nat Commun. 2019 May 21; 10(1): 2255. IF 11.878. Q1. • Principe A, Ley M, Conesa G, Rocamora R. Prediction error connectivity: A new method for EEG state analysis. Neuroimage. 2019 Mar; 188: 261-273. IF 5.812. Q1. • García-Lorenzo B, del Pino-Sedeño T, Rocamora R, López JE, Serrano-Aguilar P, Trujillo-Martín MM. Stereoelectroencephalography for Refractory Epileptic Patients Considered for Surgery: Systematic Review, Meta-Analysis, and Economic Evaluation. Neurosurgery. 2019 Feb 1; 84(2): 326-338. IF 4.605. Q1. See all Publications

Ongoing Research Projects

• Causal connectomics subtending oscillatory spread and information flow in the human brain - Financing institution: Agencia Estatal de Investigación (PCI2018-092860) - Period: from 2019 to 2021 - Principal investigator: Principe, Alessandro • Implantación de la plataforma SYLVIUS en centros especializados para cirugía de la epilepsia - Financing institution: Instituto de Salud Carlos III (DTS19/00001) - Period: from 2019 to 2021 - Principal investigator: Conesa Bertran, Gerardo See all Projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 211 Neurosciences Epilepsy

Participation in Research Networks

• Stable collaborations have been established with groups of high scientific value such as the Epilepsiezentrum of the University of Freiburg, the Epilepsieklinik of the University of Bonn, the Unité d’Epilepsie et Malaises Nuerologiques de Grenoble, the Center for Systems Neuroscience (CSN) at the University of Leicester, the Center for Brain and Cognition (CBC) at UPF (CBC), the Synthetic, Preceptive, Emotive and Cognitive Systems Group (SPECS) of IBEC and the Center for Brain Genomics (CRG). Especially relevant is the hiring of Prof. Rodrigo Quian-Quiroga from the University of Leicester as a visiting professor to lead the area of single neuron records (SNR).

Clinical Trials Signed in 2019

• Estudio de extensión abierto y multicéntrico para evaluar la seguridad y eficacia de padsevonil como tratamiento adyuvante de crisis focales en sujetos adultos con epilepsia farmacorresistente - Protocol: EP0093 - Sponsor: UCB BioSciences GmbH - Budget: 181,050 € - Period: from 2019 to 2021 - Principal investigator: Rocamora Zúñiga, Rodrigo Alberto • Estudio aleatorizado, doble ciego, controlado con placebo, multicéntrico, para evaluar la seguridad, la tolerabilidad y la eficacia del XEN1101 como tratamiento adyuvante en la epilepsia de inicio focal - Protocol: XPF-008-201 - Sponsor: Xenon Pharmaceuticals Inc. - Budget: 65,900 € - Period: from 2019 to 2022 - Principal investigator: Rocamora Zúñiga, Rodrigo Alberto

Appointments

• Since 2019, Dr. Rocamora has been appointed by CatSalut as coordinator of the Functional Unit for Epilepsy Surgery (UFCE) in Catalonia and coordinates from the Hospital del Mar all the activities carried out in our Autonomous Community in this area.

212 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Epilepsy

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Health education for people with epilepsy and families. One session every 2 months.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 213 Integrative Pharmacology and Systems Neuroscience

> Neurosciences RESEARCH GROUP

Group Leader Rafael de la Torre Fornell

[email protected]

Members Anna Boronat Rigol (PhD Student) Thais Lorenzo Díez (PhD Student) Ana María Aldea Perona (Researcher) Diego Cascales Lahoz (Technician) Arnau Busquets Garcia (Researcher) Jordi García Quintana (Technician) Aida Maria Cuenca Royo (Researcher) Noemí Haro Villaverde (Technician) Cristina Delgado Sallent (Researcher) Iris Lioba Matilla Vaz (Technician) Maria del Mar Dierssen Sotos (Researcher) Esther Menoyo Colomer (Technician) Laura Forcano Gamazo (Researcher) Juan Luis Musoles Lleó (Technician) Thomas Gener (Researcher) Pau Nebot Forcada (Technician) Àlex Gómez Gómez (Researcher) Anna Núria Palazón Zabala (Technician) Maria Gomis González (Researcher) Antoni Pastor Bosch (Technician) Olha Khymenets (Researcher) Raúl Pérez Ortuño (Technician) Elk Kossatz de Mello (Researcher) Marta Pérez Otero (Technician) Julián Andrés Mateus Rodríguez (Researcher) Iris Piera Molina (Technician) José Antonio Pascual Esteban (Researcher) Nieves Pizarro Lozano (Technician) Óscar Pozo Mendoza (Researcher) Mitona Pujadas Bastardes (Technician) María Victoria Puig Velasco (Researcher) Josep Rodríguez Morató (Technician) Patricia Robledo Montoya (Researcher) Eva Maria Vitas Gutiérrez (Research Assistant) Aleix Sala Vila (Researcher) Marta Barrera Conde (PhD Student)

214 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Integrative Pharmacology and Systems Neuroscience

The Integrative Pharmacology and Systems Neuroscience Group’s main line of research is the development of pharmacological and non-pharmacological (cognitive/electrical stimulation) approaches for the treatment of diseases that cause intellectual disability or cognitive impairment and psychiatric disorders (including Down syndrome, drug addiction, depression, schizophrenia, or dementia). Our emphasis is on understanding the underlying mechanisms of action and on developing treatments, biomarkers of exposure, efficacy and toxicity. Moreover, the group is responsible for providing instruction in pharmacology, chemistry and toxicology to graduate and undergraduate students of both human biology and medicine tracks (Pompeu Fabra University, Autonomous University of Barcelona), and to train pre-doctoral and postdoctoral researchers. The Integrative Pharmacology and Systems Neuroscience Group and the Proteomics Research Group from the Pompeu Fabra University constitute the BAPP (Bioanalysis, Proteomics and Pharmacology), a member of TECNIO, the label created by ACCIÓ which identifies the main experts in applied research and technology transfer in Catalonia. The BAPP is a reference in the field of chemistry linked to pharmacology, toxicology and the development of new drugs. The Generalitat de Catalunya has officially recognized one consolidated research group and one Emergent research group 2017-2020 included in the Integrated Pharmacology and Systems Neurosciences Research Group: Grup de Recerca Clínica en Farmacologia i Desenvolupament de Biomarcadors i Nous Fàrmacs (SGR 138) led by Rafael de la Torre, as well as an Emergent Research Group 2017-2020: Grup de Recerca en Neuroquímica i neurofisiologia de la cognició en malalties psiquiàtriques i del desenvolupament (SGR 210) led by Vicky Puig.

Main Publications

• Olesti E, Farré M, Carbó ML, Papaseit E, Perez-Mañá C, Torrens M, Yubero-Lahoz S, Pujadas M, Pozo Ó, de la Torre R. Dose-Response Pharmacological Study of Mephedrone and Its Metabolites: Pharmacokinetics, Serotoninergic Effects, and Impact of CYP2D6 Genetic Variation. Clin Pharmacol Ther 2019; 106(3): 596-604. IF 6.336. Q1. • Boronat A, Mateus J, Soldevila-Domènech N, Guerra M, Rodríguez-Morató J, Varon C, Muñoz D, Barbosa F, Morales JC, Gaedigk A, Langohr K, Covas MI, Pérez-Mañá C, Fitó M, Tyndale RF, de la Torre R. Cardiovascular benefits of tyrosol and its endogenous conversion into hydroxytyrosol in humans. A randomized, controlled trial. Free Radic Biol Med 2019; 143:471-481. IF 5.657. Q1. • Ramon-Duaso C, Gener T, Consegal M, Fernández-Avilés C, Gallego JJ, Castarlenas L, Swanson MS, de la Torre R, Maldonado R, Puig MV, Robledo P. Methylphenidate Attenuates the Cognitive and Mood Alterations Observed in Mbnl2 Knockout Mice and Reduces Microglia Overexpression. Cereb Cortex 2019; 29 (7): 2978-2997. IF 5.43. Q1.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 215 Neurosciences Integrative Pharmacology and Systems Neuroscience

• Olesti E, Rodríguez-Morató J, Gómez-Gómez A, Ramaekers JG, de la Torre R, Pozo O. Quantification of endogenous neurotransmitters and related compounds by liquid chromatography coupled to tandem mass spectrometry. Talanta 2019; 192:93-102. IF 4.9. Q1. See all Publications

Ongoing Research Projects

• Gene overdosage and comorbidities during the early lifetime in Down Syndrome - Financing institution: H2020 (2019/-999/I) - Period: from 2019 to 2024 - Principal investigator: De la Torre Fornell, Rafael • New markers of steroid profile in blood: Differentiating testosterone administration from (simultaneous) ethanol consumption (acronym: SPOLBlood) - Financing institution: World Antidoping Agency (ISF19D02JP) - Period: from 2019 to 2021 - Principal investigator: Pascual Esteban, José Antonio • Modulation of gut microbiota as a therapeutic approach to improve cognitive phenotypes of Ts65Dn mice and decelerate the onset of neurodegenerative processes - Financing institution: Fondation Jérôme Lejeune - Period: from 2019 to 2021 - Principal investigator: Pizarro Lozano, Nieves • Biomarkers of ANTidepressant RESponse: early indicators and novel targets - Financing institution: Instituto de Salud Carlos III (AC19/00020) - Period: from 2019 to 2022 - Principal investigator: Robledo Montoya, Patricia • Cognitive decline in early stages of AD after EGCG and a multimodal therapy (PENSA) (18PTC-R-592192) - Financing institution: Alzheimer’s Association - Period: from 2018 to 2020 - Principal investigator: De la Torre Fornell, Rafael See all Projects

216 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Integrative Pharmacology and Systems Neuroscience

Participation in Research Networks

• Committee for Clinical Research/Child & Developmental Committee - Financing institution: Trisomy 21 Research Society - Period: from 2017 - Principal investigator: De la Torre Fornell, Rafael • Down Syndrome and Other Genetic Developmental Disorders Network - Financing institution: European College of Neuropsychopharmacology (ECNP) - Period: from 2014 - Principal investigator: De la Torre Fornell, Rafael • European Advanced Translational Research Infrastructure for Medicine (EATRIS) - Financing institution: European Union - Period: from 2019 - Principal investigator: Pozo Mendoza, Óscar • CIBER Physiopathology of Obesity and Nutrition - Financing institution: Fondo de Investigación Sanitaria. ISCIII (CB16/12/00244) - Period: from 2019 to 2021 - Principal investigator: Fitó Colomer, Montserrat • Red de Trastornos Adictivos - Financing institution: Instituto de Salud Carlos III. Subprograma RETICS (RD16/0017/0010) - Period: from 2017 to 2021 - Principal investigator: Torrens Mèlich, Marta

Theses

• Alemany González, M. Neural correlates of memory impairment and rescue in a mouse model of Down syndrome. Universitat Pompeu Fabra - Director: Puig Velasco, María Victoria - Date of defense: 09/07/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 217 Neurosciences Integrative Pharmacology and Systems Neuroscience

Outreach

Dissemination to Society and Initiatives of Citizen Participation

• Anna Boronat, Josep Rodríguez-Morató. Students of the Arnau Cadell Institute visit the Laboratory of Integrative Pharmacology and Systems Neuroscience. ACCÉS Project (Bringing Science Closer to Secondary Schools) included in the Escolab Project. Barcelona Science Programme of the Institute of Culture. 26 April 2019. • Anna Boronat, Josep Rodríguez-Morató. BioJunior. Bring science to secondary school students through different activities, visits to labs and scientific talks. Parc Recerca Biomèdica de Barcelona (PRBB), 3 May 2019. • Vicky Puig, Programme Committee. 3rd International Conference Trisomy21 Research Society. CosmoCaixa, Barcelona, 8 June 2019. • Rafael de la Torre. Viure pensant en un cervell actiu. Centre Cívic Barceloneta, Barcelona, 9 December 2019. • Anna Boronat. Visit to the Laboratory of Integrative Pharmacology and Systems Neuroscience for students of Pharmacy (3rd year) from Universitat Blanquerna. 25 October 2019. • Rafael de la Torre. Envelliment actiu, cervell jove. Students from Fundació Universitària del Bages. 14 March 2019. • Maria Victòria Puig. Ritmes cerebrals per curar la discapacitat intel·lectual. Olimpíada de Biologia 2019. 15 February 2019. • Natàlia Soldevila, Laura Forcano, Rafael de la Torre. Citizen participation in the design of the PENSA Study on prevention of cognitive impairment in people with subjective cognitive decline: a co-creation project. Barcelona, 25 October 2019.

218 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Mental Health

> Neurosciences RESEARCH GROUP

Group Leader Group Leader Víctor Pérez Sola Francesc Colom Victoriano

[email protected] [email protected]

Members Alicia Valiente Gómez (Researcher) Sílvia Oller Canet (PhD Student) Pilar Álvarez López (Researcher) Aitana García Estela (Technician) María Teresa Campillo Sanz (Researcher) Bridget Hogg (Technician) Matilde Elices (Researcher) Alba Toll Privat (Technician) Marc Grifell Guàrdia (Researcher) Núria Viñeta Garí (Technician) Antonio Luis Palomo Nicolau (Researcher) Eva Luque Asín (Research Assistant) Núria Pujol Giménez (Researcher) Alfonso Rodríguez Martínez (Researcher)

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 219 Neurosciences Mental Health

The Mental Health Research Group is a multidisciplinary team formed by researchers from several fields of mental health. Currently, the group has three main areas of research: • E-mental Health: our group pioneers the design, research and implementation of online tools devised to provide a user-friendly, accessible, efficient, scalable and cheaper treatment of mood and anxiety disorders. Several outstanding projects are ongoing in this area: - Ifightdepression: this is an online CBT-inspired treatment aimed at dealing with mild and moderate depression. Our group is running the largest efficiency trial with this tool, advocating for its implementation and training ad-hoc therapists. - SIMPLe: an Android and IOS app designed by our researchers that aims to provide online psychoeducation, symptom monitoring, adherence enhancement and crisis prevention in bipolar disorder. An RCT is currently under way. - We currently have several brand-new tools on our work benches, including e-EMDR, a subthreshold anxiety management online kit and others. • Personalized interventions for treatment-refractory patients: our group uses novel and groundbreaking pharmacological and psychotherapeutic approaches to deal with treatment-refractory patients. Similarly, the group works with several large consortiums aiming to identify new biomarkers of treatment response. The following are some examples: - Impact of trauma and the efficacy of EMDR with: PTSD, bipolar disorders, schizophrenia, alcohol dependence, immigration related trauma, etc. - Psychosurgery in refractory anorexia. - Psilocybin and ketamine in refractory depression. - Neuroimaging and pharmacogenetics in the prediction of response to lithium. • Neuroimaging. Our group studies the brain and behavior correlations using anatomical and functional MRI. Significant contributions have been made in the field of obsessive-compulsive disorder, anxiety, chronic pain, psychopathy and rare genetic disorders.

Main Publications

• Argyelan M, Oltedal L, Deng ZD, Wade B, Bikson M, Joanlanne A, Sanghani S, Bartsch H, Cano M, Dale AM, Dannlowski U, Dols A, Enneking V, Espinoza R, Kessler U, Narr KL, Oedegaard KJ, Oudega ML, Redlich R, Stek ML, Takamiya A, Emsell L, Bouckaert F, Sienaert P, Pujol J, Tendolkar I, van Eijndhoven P, Petrides G, Malhotra AK, Abbott C. Electric field causes volumetric changes in the human brain. eLife 2019; 8: e49115. IF 7.551. D1.

220 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Mental Health

• Camprodon-Rosanas E, Pujol J, Martínez-Vilavella G, Blanco-Hinojo L, Medrano- Martorell S, Batlle-Vila S, Forns J, Ribas-Fitó N, Dolz M, Sunyer J. Brain Structure and Function in School-Aged Children With Sluggish Cognitive Tempo Symptoms. J Am Acad Child Psy 2019; 58(2): 256-266. IF 6.391. D1. • Pujol J, Harrison BJ, Contreras-Rodríguez O, Cardoner N. The contribution of brain imaging to the understanding of psychopathy. Psychol Med 2019; 49(1): 20-31. IF: 5.641. D1. • Pujol J, Blanco-Hinojo L, Macià D, Alonso P, Harrison BJ, Martínez-Vilavella G, Deus J, Menchón JM, Cardoner N, Soriano-Mas C. Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder. Cereb Cortex 2019; 29(11): 4753-4762. IF: 5.437. Q1. • Kalman JL, Papiol S, Forstner AJ, Heilbronner U, Degenhardt F, Strohmaier J, Adli M, Adorjan K, Akula N, Alda M, et al. (Colom F). Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study. Bipolar Disord 2019; 21(1): 68-75. IF: 4.936. Q1. See all Publications

Ongoing Research Projects

• Estudio del estado de activación del factor Nrf2 en cultivo primario de pro-neuronas a partir de epitelio olfatorio en el Trastorno Depresivo Mayor - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00398) - Period: from 2016 to 2020 - Principal investigator: Álvarez López, Pilar • Single-blind, Randomized Controlled Comparison of EMDR Versus Supportive Therapy in Affective Relapse Prevention in Bipolar Patients With a History of Trauma - Financing institution: Brain & Behavior Research Foundation (24397) - Period: from 2017 to 2020 - Principal investigator: Amann, Benedikt Lorenz • Estimulación cerebral profunda en el cíngulo subgeniculado y el núcleo accumbens como tratamiento a pacientes con anorexia nerviosa crónica, severa y refractaria - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00382) - Period: from 2017 to 2019 - Principal investigator: Pérez Sola, Víctor • Optimizing response to Li treatment through personalized evaluation of individuals with bipolar I disorder: the R-LiNK initiative - Financing institution: European Commission (754907) - Period: from 2018 to 2022 - Principal investigator: Colom Victoriano, Francesc

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 221 Neurosciences Mental Health

• Estudi simple cec, aleatoritzat i controlat per comparar l’eficàcia de l’EMDR vs. TAU en pacients amb trastorn per ús de substàncies i història de trauma psicològic - Financing institution: Departament de Salut de la Generalitat de Catalunya (SLT006/17/00038) - Period: from 2018 to 2020 - Principal investigator: Amann, Benedikt Lorenz See all Projects

Participation in Research Networks

• CIBERSAM – Centro de Investigación Biomédica en Red de Salud Mental - Financing institution: Fondo de Investigación Sanitaria. Subprograma CIBER. (CB07/09/0010) - Period: from 2014 to 2019 - Principal investigator: Pérez Sola, Víctor

222 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurofunctionality and Brain Language

> Neurosciences RESEARCH GROUP

Group Leader Members Jordi Peña Casanova Rosa M. Manero Borràs (Researcher) [email protected] Víctor Manuel Puente Périz (Researcher) Albert Puig Pijoan (Researcher) Gloria Villalba Martínez (Researcher) Aida Fernández Lebrero (Technician) Greta García Escobar (Technician) Núria Massuet Pujadas (Technician) Gonzalo Sánchez Benavides (Technician)

The Neurofunctionality and Brain Language Research Group focuses on the study of the relationships between cognition, behavior, emotional states and the brain, with a special interest in language. These relationships are studied in the context of focal and diffuse brain damage, specifically, in neurodegenerative diseases. The research group’s traditional areas of work are aimed at the development, standardization and validation of instruments for diagnosing and measuring cognitive abilities. The group places particular emphasis on the following neurological pathologies: Alzheimer’s disease, mild cognitive impairment, vascular dementia, Lew Body dementia. The master’s students in Neuropsychology and Behavioural Neurology from the Psychiatry and Legal Medicine department of the Autonomous University of Barcelona are actively involved in the research group.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 223 Neurosciences Neurofunctionality and Brain Language

The research group collaborates with the Neurosurgery Department (Dr. Gerard Conesa) in functional brain mapping studies, in which electrical stimulation of the cerebral cortex in vigil patients is carried out. These studies make high-level neurosurgery possible, which brings unquestionable benefits for the patients, given that during the surgical procedure, the cognitive brain regions can be distinguished and protected from physical damage.

Main Publications

• Emerson RL, García-Molina A, López-Carballo J, García-Fernández J, Aparicio-López C, Novo J, Sánchez-Carrión R, Enseñat-Cantallops A, Peña-Casanova J. Visual search in unilateral spatial neglect: The effects of distractors on a dynamic visual search task. Appl Neuropsychol Adult 2019; 26(5): 401-410. IF 1.548. Q3. See all Publications

Clinical Trials Signed in 2019

• Monitorización de la movilidad de enfermos de Parkinson con fines terapéuticos - ensayo clínico - Protocol: INV_PROC_A118 - Sponsor: Consorci Sanitari del Garraf - Budget: No economic compensation - Principal investigator: Puente Périz, Víctor Manuel • Estudio en fase III, de 4 semanas de duración, multicéntrico, aleatorizado, doble ciego, controlado con placebo y de grupo paralelo de TD 9855 en el tratamiento de la hipotensión ortostática neurogénica sintomática en sujetos con fallo autonómico primario - Protocol: 0169 - Sponsor: Therevance Biopharma - Budget: 23,510 € - Principal investigator: Puente Périz, Víctor Manuel • A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of TD 9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure - Protocol: 0170 - Sponsor: Therevance Biopharma - Budget: 16,172 € - Principal investigator: Puente Périz, Víctor Manuel

224 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Neurofunctionality and Brain Language

• Registro clínico post-autorización para evaluar las prestaciones clínicas de un dispositivo polimérico (Cranial COVER™) para cubrir el agujero del trépano - Protocol: NEO-COV-2018-01 - Sponsor: Neos Surgery - Budget: 1,920 € - Principal investigator: Villalba Martínez, Gloria

Theses

• Martín de la Huerga N. Extensión del estudio multicéntrico de normalización y validación de instrumentos neurocognitivos y funcionales en sujetos jóvenes (neuronorma jóvenes - extensión 2) y perfiles cognitivos de pacientes con esclerosis múltiple mediante la batería neuropsicológica neuronorma. Universitat Autònoma de Barcelona - Directors: Peña Casanova, Jordi; Sánchez-Benavides, Gonzalo - Date of defense: 29/11/2019

Outreach

Conferences, Seminars and Courses

• Peña Casanova J. Exploración neuropsicológica: avances conceptuales y tecnológicos. Presentación del Test Barcelona-2 y de la Estación de Trabajo Neuropsicológico online. • Taller y jornada de Neuropsicología y Neurología de la Conducta. Unitat Docent Mar, Universitat Autònoma de Barcelona, 16-17 May 2019. • Villalba G, Salgado P, Gines JM, Manero RM, Medrano S, Delgado I, Conesa C, Guardiola R, Cedrón C, Faus G, Pérez V. Deep brain stimulation in patients with Anorexia Nervosa. Preliminary results of the clinical trial NCT03168893. Congreso de la Sociedad Internacional de Neuromodulación (INS). Sidney. 26-29 May 2019. • Villalba G. Resultados preliminares del ensayo clínico: NCT03168893: estimulación cerebral profunda en el cíngulo subgeniculado y en el núcleo accumbens en pacientes con anorexia nerviosa crónica, severa y refractaria. Congreso de la Sociedad Española de Neurocirugía Funcional (SENFE). Bilbao, 4 October 2019. • Villalba G. DBS en pacientes con trastornos de la conducta alimentaria. Congreso del Capítulo Español de Sociedad Internacional de Neuromodulación (INS España). Madrid. 27 September 2019.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 225 Perioperative Medicine and Pain

> Neurosciences RESEARCH GROUP

Group Leader Members Lluís Gallart Gallego Juan Carlos Álvarez García (Researcher) [email protected] Elvira Bisbe Vives (Researcher) Christian Dürsteler Tatxe (Researcher) Fernando Escolano Villén (Reseracher) Jordi Vallés Esteve (Researcher) Anna Mases Fernàndez (Researcher) Lluís Moltó Garcia (Researcher) Antonio Montes Pérez (Reseracher) Francesc Xavier Santiveri Papiol (Researcher) Maria Teresa Silva Costa Gómes (Researcher) Lluís Aguilera Cuchillo (PhD Student) Sílvia Bermejo Martínez (PhD Student) Eulàlia Obrador González (Technician)

We are clinical anesthesiologists who also perform clinical research. Our main topics are: (1) Respiratory aspects of anesthesia, namely treatment of perioperative hypoxemia, effects of anesthestics on respiratory function and postoperative pulmonary complications; (2) Blood saving strategies, focused to avoid blood transfusion; (3) Neuroanaesthesia, mainly monitoring depth of anaesthesia and effects of anaesthetics during neuroanaesthesia; (4) Clinical trials related to anaesthetic procedures; (5) Pathophysiological mechanisms of neuropathic pain; (6) Epidemiology and treatment of postoperative pain.

226 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Perioperative Medicine and Pain

Main Publications

• Ois A, Vivas E, Figueras-Aguirre G, Guimaraens L, Cuadrado E, Avellaneda C, Bertran-Recasens B, Rodríguez-Campello A, Gracia-Arnillas MP, Villalba G, Saldaña J, Capellades J, Fernández-Candil JL, Roquer J. Misdiagnosis Worsens Prognosis in Subarachnoid Hemorrhage With Good Hunt and Hess Score. Stroke 2019; 50(11): 3072-3076. IF 6.046. Q1. • Benítez-Cano A, de Antonio-Cuscó M, Luque S, Sorli L, Carazo J, Ramos-Delgado I, Bermejo S, Campillo N, Horcajada JP, Samsó E, Grau S. Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia. J Antimicrob Chemother 2019; 74(11): 3268-3273. IF 5.113. Q1. • Russotto V, Sabaté S, Canet J, Rojo A, of the European Society of Anaesthesiology (ESA) Clinical Trial Network (...Arroyo R, Cabrera JC, Carazo J, Gallart L, Santiveri X...). Development of a prediction model for postoperative pneumonia: A multicentre prospective observational study. Eur J Anaesthesiol 2019; 36(2): 93-104. IF 4.14. Q1. • Gómez-Ramírez S, Bisbe E, Shander A, Spahn DR, Muñoz M. Management of Perioperative Iron Deficiency Anemia. Acta Haematol-Basel 2019; 142(1): 21-29. IF 1.313. Q4. • Castells A, Bisbe E, Petit M, Soler M, Padrós J, Grupo de trabajo del Consell de Col·legis de Metges de Catalunya para la elaboración del documento de posición Principios y deberes en el ejercicio de la dirección médica de los hospitales y centros sanitarios. Med Clin (Barc) 2019; 153(12): 467-469. IF 1.277. Q3. See all Publications

Ongoing Research Projects

• Validación externa prospectiva de una escala predictiva de la cronificación de dolor crónico post-quirúrgico - Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI16/00279) - Period: from 2017 to 2019 - Principal investigator: Montes Pérez, Antonio See all Projects

Theses

• Aguilera L. Pressió generada per la tos. Tècniques alternatives de mesura i efectes de l’analgèsia epidural i la laparotomia mediana. Universitat Autònoma de Barcelona - Director: Gallart Gallego, Lluís - Date of defense: 29/11/2019

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 227 Behavioural Neurobiology

> Neurosciences ASSOCIATED GROUP

Group Leader Members Olga Valverde Granados Ana Martín Sánchez (Researcher) [email protected]

The Behavioural Neurobiology Research Group was constituted in 2007 and is a recognized team in the study of the neurobiological substrate of neuropsychiatric disorders and neurotoxicity, including drug addiction, affective disorders, the consequences of early alcohol exposure and psychiatric co-morbidity. To address our objectives, we use behavioural models in rodents and biochemical and molecular techniques in particular brain areas. Our group belongs to the Experimental and Health Sciences Department of Pompeu Fabra University and is located in the Barcelona Biomedical Research Park. Our team is member of the Addictive Disorders Network (Red de Trastornos Adictivos RTA-ISCIII) and was integrated in the Neurosciences Programme of IMIM for the translational research activity undertaken.

228 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Behavioral Neurobiology

Main Publications with IMIM

• Ferrer-Pérez C, Castro-Zavala A, Luján MÁ, Filarowska J, Ballestín R, Miñarro J, Valverde O, Rodríguez-Arias M. Oxytocin prevents the increase of cocaine-related responses produced by social defeat. Neuropharmacology 2019; 146: 50-64. IF 4.367. Q1. • Bilbao A, Leixner S, Wei S, Cantacorps L, Valverde O, Spanagel R. Reduced sensitivity to ethanol and excessive drinking in a mouse model of neuropathic pain. Addict Biol 2019; 24(5): 1008-1018. IF 4.223. Q1. • Luján MÁ, Cantacorps L, Valverde O. The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake. Addict Biol 2019: e12778. IF 4.223. Q1. • Cantacorps L, Alfonso-Loeches S, Guerri C, Valverde O. Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation. J Psychopharmacol 2019; 33(12): 1562-1572. IF 4.221. Q1. • Montagud-Romero S, Cantacorps L, Valverde O. Histone deacetylases inhibitor trichostatin A reverses anxiety-like symptoms and memory impairments induced by maternal binge alcohol drinking in mice. J Psychopharmacol 2019; 33(12): 1573- 1587. IF 4.221. Q1.

Theses

• Cantacorps Centellas L. Effects of maternal binge alcohol consumption on emotional, cognitive and addictive behavior in mice. Universitat Pompeu Fabra - Director: Valverde Granados, Olga - Date of defense: 15/11/2019

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> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 229 Genetics

> Neurosciences ASSOCIATED GROUP

Group Leader Members Luis Alberto Pérez Jurado Gemma Aznar Laín (Researcher) [email protected] Andrés Medrano Muñoz (Researcher) Montserrat Pujadas Lorente (Researcher)

The UPF Genetics Unit is a research group associated with IMIM. The group also belongs to the Network Center for Biomedical Research in Rare Diseases (CIBERER). Our research focuses on genomic structural variation and several neurodevelopmental genetic disorders affecting behavior, language and personality, including mutational mechanisms, evolutionary studies, and the use of animal and cellular models of disease. We also coordinate a collaborative program aimed at providing support to the health care system in diagnosing unsolved rare diseases through the use of genomic and personalized medicine. We aim to translate our research findings directly into clinical practice, by improving clinical protocols and diagnostic tools, and developing novel therapies.

230 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Genetics

Main Publications with IMIM

• Codina-Solà M, Costa M, Pérez-García D, Flores R, Palacios M, Cusco I, Pérez-Jurado L. Genetic factors contributing to autism spectrum disorder in Williams-Beuren syndrome. J Med Genet 2019; 56(12): 801-808. IF 5.899. Q1. • Ruiz-Arenas C, Cáceres A, López-Sánchez M, Tolosana I, Pérez-Jurado L, González JR. scoreInvHap: Inversion genotyping for genome-wide association studies. PLoS Genet 2019; 15(7): e1008203. IF 5.224. Q1. • MacLennan AH, Lewis S, Moreno-De-Luca A, Fahey M, Leventer RJ, McIntyre S, Ben- Pazi H, Corbett M, Wang X, Baynam G, Fehlings D, Kurian MA, Zhu C, Himmelmann K, Smithers-Sheedy H, Wilson Y, Ocaña CS, van Eyk CL, Badawi N, Wintle RF, Jacobsson B, Amor DJ, Mallard C, Pérez-Jurado L, Hallman M, Rosenbaum PJ, Kruer MC, Gecz J. Genetic or Other Causation Should Not Change the Clinical Diagnosis of Cerebral Palsy. J Child Neurol 2019; 34(8): 472-476. IF 2.092. Q2.

Ongoing Research Projects with IMIM

• Implementació de la medicina personalitzada basada en la genòmica en malalties minoritàries neurològiques no diagnosticades - Financing institution: Departament de Salut, Generalitat de Catalunya (SLT002/16/00174) - Period: from 2017 to 2019 - Principal investigator: Pérez Jurado, Luis Alberto

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> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 231 Laboratory of Neuropharmacology

> Neurosciences ASSOCIATED GROUP

Group Leader Rafael Maldonado López

[email protected]

The Laboratory of Neuropharmacology (NeuroPhar) is a UPF research group associated with the IMIM. NeuroPhar studies the neurobiological substrate of drug addiction, pain, cognitive deficits, affective and eating disorders. The main interest of this research group is the development of research lines aimed at the identification of new therapeutic targets in the central nervous system. The Laboratory of Neuropharmacology is particularly interested in the involvement of the endogenous opioid and cannabinoid systems in these pathological processes.

Main Publications with IMIM

• Ramon-Duaso C, Gener T, Consegal M, Fernández-Avilés C, Gallego JJ, Castarlenas L, Swanson MS, de la Torre R, Maldonado R, Puig MV, Robledo P. Methylphenidate Attenuates the Cognitive and Mood Alterations observed in Mbnl2 Knockout mice and Reduces Microglia Overexpression. Cereb Cortex 2019; 29(7): 2978-2997. IF 5.437. Q1.

232 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Laboratory of Neuropharmacology

• Martínez-Navarro M, Lara-Mayorga IM, Negrete R, Bilecki W, Wawrzczak-Bargieła A, Gonçalves L, Dickenson AH, Przewłocki R, Baños JE, Maldonado R. Influence of behavioural traits in the inter-individual variability of nociceptive, emotional and cognitive manifestations of neuropathic pain. Neuropharmacology 2019; 148: 291- 304. IF 4.367. Q1.

Theses

• Carcolé Estrada, M. Role of the sigma-1 receptor in the pathophysiology of osteoarthritis pain. Universitat Pompeu Fabra - Directors: Maldonado López, Rafael; Cabañero, D - Date of defense: 5/12/2019

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> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 233 Neuroimaging of Mental Disorders

> Neurosciences ASSOCIATED GROUP

Group Leader Members Òscar Vilarroya Oliver Daniel Bergé Baquero (Researcher) [email protected] Romina Cortizo Vidal (Researcher)

This group is a multidisciplinary research group with the objective of studying the neuroanatomical and neurofunctional bases of specific mental and neurological disorders, as well as specific cognitive, emotional and motivational functions among the general population, using structural and functional magnetic resonance techniques. At present, the group has the following research lines active in neuroimaging: Attention Deficit Hyperactivity Disorder and other impulsivity disorders, schizophrenia and other psychotic disorders, anxiety disorders, and other studies in the general population, such as brain and metabolomic changes induced by pregnancy.

234 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Neuroimaging of Mental Disorders

Main publications with IMIM

• Hoogman M, Muetzel R, Guimaraes JP, Shumskaya E, ENIGMA Group… (Vilarroya O). Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples. Am J Psychiatry 2019; 176(7): 531-542. IF 13.655. Q1. • Treen D, Savulich G, Mezquida G, García-Portilla MP, Toll A, García-Rizo C, García- Álvarez L, Bergé D, Bobes J, Bernardo M, Fernández-Egea E, Mané A. Influence of secondary sources in the Brief Negative Symptom Scale. Schizophr Res 2019; 204: 452-454. IF 4.569. Q1. • Pretus C, Marcos-Vidal L, Martínez-García M, Picado M, Ramos-Quiroga JA, Richarte V, Castellanos FX, Sepulcre J, Desco M, Vilarroya O, Carmona S. Stepwise functional connectivity reveals altered sensory-multimodal integration in medication-naïve adults with attention deficit hyperactivity disorder. Hum Brain Mapp 2019; 40(16): 4645- 4656. IF 4.554. Q1. • Pretus C, Hamid N, Sheikh H, Gómez Á, Ginges J, Tobeña A, Davis R, Vilarroya O, Atran S. Ventromedial and dorsolateral prefrontal interactions underlie will to fight and die for a cause. Soc Cogn Affect Neurosci 2019; 14(6): 569-577. IF 3.662. Q1. • Hamid N, Pretus C, Atran S, Crockett MJ, Ginges J, Sheikh H, Tobeña A, Carmona S, Gómez A, Davis R, Vilarroya O. Neuroimaging ‘will to fight’ for sacred values: an empirical case study with supporters of an Al Qaeda associate. R Soc Open Sci 2019; 6(6): 181585. IF 2.515. Q2.

Ongoing Research Projects with IMIM

• Molecular and neuronal markers as prognostic tools for the evolution of first episode psychosis and the modulating effects of cannabis - Financing institution: Proyectos de Investigación en Salud. ISCIII (PI18/00053) - Period: from 2018 to 2021 - Principal investigator: Bergé Baquero, Daniel (Co-PI)

Awards

• Daniel Bergé Baquero. Clinical award for the best clinical challenge. Societat Catalana de Psiquiatria i Salut Mental 2019.

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> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 235 Physiology of Cognition and Alzheimer’s Prevention

> Neurosciences RESEARCH GROUP

Group Leader Members José Luis Molinuevo Guix Raffaele Cacciaglia (Researcher) [email protected] Noemí Carranza Herrezuelo (Researcher) Marta Crous Bou (Researcher) Carles Falcon Falcon (Researcher) Juan Domingo Gispert López (Researcher) José María González de Echávarri (Researcher) Oriol Grau Rivera (Researcher) Eider Martínez de Arenaza Urquijo (Researcher) Carolina Minguillón Gil (Researcher) Grégory Operto (Researcher) Aleix Sala Vila (Researcher) Gonzalo Sánchez Benavides (Researcher) Marc Suárez Calvet (Researcher) Anna Brugulat Serrat (PhD Student) Marta Milà Alomà (PhD Student) Gemma Salvadó Blasco (PhD Student) Mahnaz Shekari (PhD Student)

Our group’s main aim is to understand the biological processes that precede the onset of Alzheimer’s disease and its clinical manifestations. This will lead to establishing prevention programmes to halt, or at least delay, the onset of cognitive impairment and,

236 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Neurosciences Physiology of Cognition and Alzheimer’s Prevention

ultimately, dementia, in asymptomatic people at risk of developing the disease. We are a group affiliated with the Barcelonaβeta Brain Research Centre (BBRC), the research centre of the Pasqual Maragall Foundation. Recent studies have demonstrated that Alzheimer’s disease pathology develops over decades before the clinical symptoms appear; this silent, asymptomatic period is known as the pre-clinical phase of Alzheimer’s disease. Detecting and understanding this preclinical stage generates opportunities for developing new therapeutic strategies. For this reason, it has been hypothesised that, in order to increase the chances of success, drugs that have failed in trials involving symptomatic patients should be tested in cognitively unimpaired individuals who have a high risk of developing the disease. The Alfa Study is the basis for establishing protocols and research studies, both observational and interventional, for participants at risk of cognitive impairment due to Alzheimer’s disease. Alfa participants are invited, according to their characteristics, willingness, and availability, to take part in Alzheimer’s prevention studies. In addition to the Alfa study and related sub-studies, we also investigate people with mild symptoms (subjective memory complaints and mild cognitive impairment).

Main publications with IMIM

• Ewers M, Franzmeier N, Suárez M, Morenas-Rodríguez E, Caballero MAA, Kleinberger G, Piccio L, Cruchaga C, Deming Y, Dichgans M, Trojanowski JQ, Shaw LM, Weiner MW, Haass C, Alzheimer’s Disease Neuroimaging Initiative. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease. Sci Transl Med 2019; 11(507): eaav6221. IF 17.161. Q1. • Ashton NJ, Suárez-Calvet M, Heslegrave A, Hye A, Razquin C, Pastor P, Sánchez- Valle R, Molinuevo JL, Visser PJ, Blennow K, Hodges AK, Zetterberg H. Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers. Alzheimers Res Ther 2019; 11: 94. IF 6.142. Q1.

Theses

• Brugulat-Serrat, A. Impact of Alzheimer’s disease risk factors on white matter hyperintensities and cognition in cognitively unimpaired individuals. Universitat Pompeu Fabra - Directors: Molinuevo Guix, José Luis; Gispert, JD; Gramunt, N - Date of defense: 21/06/2019

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> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 237

Facts and Figures

> Core Facilities > Internal Services > Common Areas and Laboratories > Internal and External Services > Other Services

> Research Activity > Scientific Publications > Research Grants and Transfer of Results > Clinical Guidelines > Committees > Scientific Advisory Board

> Management > Management Structure > Income > Human Resources > Quality > Communication > Governing Bodies

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 239 Facts and Figures

CORE FACILITIES

> Internal Services > Common Areas and Laboratories > Internal and External Services > Other Services

Montserrat Torà Barnadas (head of service)

Magdalena Arnal Segura Lara Nonell Mazelón Marta Bódalo Torruella Eulàlia Puigdecanet Riubugent Laia Bojar Chicharro Eulàlia Puigmartí Pich Miquel Clarós Jorge Alicia Redón Peyró Xavier Duran Jordà Rebeca Rueda Miret Montserrat Hidalgo Salgado Lidia Ruiz Moya Piedad Navarro Moya Núria Somoza Abelló

240 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

The Scientific and Technical Services (SCT) are a variety of services created with the objective of providing researchers with both scientific and technical support and the infrastructure necessary to carry out experimental research. Each service has a specific highly qualified staff responsible of daily functioning and scientific advisement under a SCT unique general manager that is in charge of coordination and organization.

The services offered are based on: • Scientific consulting and advisement • Common laboratories and experimental areas with specific legal and technical requirements • Highly technological equipment for biomedical research

Services are organized under three main areas: • Internal Services • Common Areas and Laboratories • Internal and External Services

Scientific and Technical Services have the Quality Management System Certification under ISO 9001:2015. Besides using its Scientific and Technical Services (SCT), IMIM researchers can also have access to those belonging to the CRG and the UPF, located in the same building of the PRBB. These SCT add to and complement the services already available, covering fields such as Genomics, Proteomics, Cytometry and Microscopy. .

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 241 Facts and Figures · Core Facilities

Internal Services

Consulting Service on Methodology for Biomedical Research

The objective of the Consulting Service on Methodology for Biomedical Research (AMIB) is to offer support on methodology and statistics applied to biomedical research to investigators of Parc de Salut Mar (PSMAR) health care centers and IMIM. The services offered are: • Consultation regarding protocol design • Sample size estimation • Creation of randomization lists • Design, management and quality control of data bases • Statistical analysis • Report writing • Consulting on presentations and publications

Activity 2019

Centre n % IMIM (PSMAR) 354 60% PSMAR (no IMIM) 236 40% Total 590 100%

Consultation by IMIM research programme 2019

Research programme n % Cancer 112 31% Epidemiology and Public Health 28 8% Neurosciences 31 9% Inflammatory and Cardiovascular Disorders 181 51% SCT 2 1% Total 464 100%

242 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

Consultations by PSMAR centers 2019

Programme n % Laboratori de Referència de Catalunya 6 3% CAP Barceloneta 8 3% Institut de Neuropsiquiatria i Addiccions 2 1% Hospital del Mar 220 93% Total 236 100%

Publications

AMIB members have appeared in the author lists of articles in a total of 20 publications and those with the highest impact factor are highlighted: • Marco E, Sánchez-Rodríguez D, Dávalos-Yerovi VN, Duran X, Pascual EM, Muniesa JM, Rodríguez DA, Aguilera-Zubizarreta A, Escalada F, Duarte E. Malnutrition according to ESPEN consensus predicts hospitalizations and long-term mortality in rehabilitation patients with stable chronic obstructive pulmonary disease. Clin Nutr 2019; 38(5): 2180-2186. IF 6.402. Q1. • Sánchez-Rodríguez D, Marco E, Ronquillo-Moreno N, Maciel-Bravo L, Gonzales- Carhuancho A, Duran X, Guillén-Solà A, Vázquez-Ibar O, Escalada F, Muniesa JM. ASPEN-AND-ESPEN: A postacute-care comparison of the basic definition of malnutrition from the American Society of Parenteral and Enteral Nutrition and Academy of Nutrition and Dietetics with the European Society for Clinical Nutrition and Metabolism definition. Clin Nutr 2019; 38(1): 297-302. IF 6.402. Q1. • Sánchez-Rodríguez D, Marco E, Schott AM, Rolland Y, Blain H, Vázquez-Ibar O, Escalada F, Duran X, Muniesa JM, Annweiler C. Malnutrition according to ESPEN definition predicts long-term mortality in general older population: Findings from the EPIDOS study-Toulouse cohort. Clin Nutr 2019; 38(6): 2652-2658. IF 6.402. Q1. • Hardy-Werbin M, Rocha P, Arpí O, Taus Á, Nonell L, Durán X, Villanueva X, Joseph- Pietras D, Nolan L, Danson S, Griffiths R, López-Botet M, Rovira A, Albanell J, Ottensmeier C, Arriola E. Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer. Oncoimmunology 2019; 8(6): e1593810. IF 5.333. Q1. • Dávalos-Yerovi V, Marco E, Sánchez-Rodríguez D, Guillen-Solà A, Duran X, Pascual EM, Muniesa JM, Escalada F, Duarte E. Sarcopenia According to the Revised European Consensus on Definition and Diagnosis (EWGSOP2) Criteria Predicts Hospitalizations and Long-Term Mortality in Rehabilitation Patients With Stable Chronic Obstructive Pulmonary Disease. J Am Med Dir Assoc 2019; 20(8): 1047-1049. IF 4.899. Q1.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 243 Facts and Figures · Core Facilities

• Gómez-Martín I, Moreno S, Duran X, Pujol RM, Segura S. Diagnostic Accuracy of Non-melanocytic Pink Flat Skin Lesions on the Legs: Dermoscopic and Reflectance Confocal Microscopy Evaluation. Acta Derm Venereol 2019; 99(1): 33-40. IF 3.531. Q1. • Hernández-Ruiz E, Hernández-Muñoz I, Masferrer E, Ferrándiz-Pulido C, Andrades E, Gimeno J, Duran X, García-Patos V, Pujol RM, Toll A. A Myxoid Fibrotic Reaction Pattern is Associated with Metastatic Risk in Cutaneous Squamous Cell Carcinoma. Acta Derm Venereol 2019; 99(1): 89-94. IF 3.531. Q1. • Roviralta-Vilella M, Moreno-Poyato AR, Rodríguez-Nogueira Ó, Duran-Jordà X, Roldán-Merino JF; MiRTCIME.CAT Working Group. Relationship between the nursing practice environment and the therapeutic relationship in acute mental Health units: A cross-sectional study. Int J Ment Health Nurs 2019; 28(6): 1338-1346. IF 2.433. Q1.

Freezers and Cryopreservation

This service is dedicated to the maintenance and supervision of the centralized -20°C and -80°C large freezers area as well as the liquid nitrogen area.

Services

• Monitoring of the process of supplying liquid nitrogen to the tanks • Monitoring of the process of refilling the nitrogen tanks • Process of supplying liquid nitrogen to portable containers • Monitoring of proper freezer operation with a system of alarms connected to the IMIM Maintenance Service • Assignment of space in the -80ºC freezers and LN2 containers • Temperature control of all refrigeration units and issuing of reports • Storage and distribution of dry ice • Technical support and scientific consultancy and advisement

Equipment

• 68 freezers of -80ºC ultra-low temperature • 4 temperature-controlled rooms (Temp and O2 control in one room) • 3 chambers of -20ºC • 4 chambers of 4ºC • 3 combined refrigerator/freezers (double sensor) • 5 refrigerators • 8 freezers of -20ºC

244 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

All the equipment has sensors to monitor the different parameters of the units. Every week, the temperature records are sent to the different research groups that use the equipment. A total of 12 new requests for cryopreservation space were processed in 2019.

Cell Culture Service

Services

• Preparation of cell culture media on demand. A total of 1,074 culture media were prepared under request. • Mycoplasma test. A total of 309 applications for the mycoplasma test were received.

Cell line maintenance service

The bank has more than 140 tumor and normal cell lines, kept frozen in liquid nitrogen. The service includes maintenance of cell lines, replacement of stocks and distribution of frozen vials to internal users under request. Number of requests in 2019: 99

Sterilization and Cleaning

The Sterilization and Cleaning Service provides support for the research laboratories in keeping the facilities clean (lab tables, fume-cupboard glass, cabinets), as well as taking care of fungible material. The service carries out daily sterilization controls and all records and reports are filed for examination.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 245 Facts and Figures · Core Facilities

Common Areas and Laboratories

Histology

The Histology Area consists of a laboratory with the necessary infrastructure for processing tissues.

Equipment

• Leica Cryostat Microtome • Paraffin microtome • Dual view optical microscope • ZEISS optical microscope • Selecta oven up to 200ºC • Leika paraffin dispenser • Myr paraffin-block dispenser • Cooling and heating plates • Heating baths • Refrigerator

Microscopy

The Microscopy Area consists of two different areas:

Microscopy Room

• 2 Fluorescence Microscopes (Microscopy BX61 Olympus and Motorized Microscopy Nikon Eclipse Ni-E), equipped with a system for recording digital images • 1 Dual-view optical microscope

Transmission Electron Microscopy

The service is offered only under collaboration or self-service for staff instructed in their use and functioning: • Advisement in preparation of samples for their study with the electron microscope • Observation and study of samples with the electron microscope • Electronic micrographs (analog and digital photography reprints) taken from the samples

246 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

• Interpretation of the electron micrographs and results obtained from the study samples The types of samples suitable for study (always from human or animal tissue samples) are the following: culture of cells processed using the mono-layer or roll procedure; samples from any human or animal organ or tissue, including blood, multiple fluids with cells and cilia samples; and microbiological samples in tissues or microbiological samples coming from cultures.

Radioactive Facilities

The Scientific and Technical Services of IMIM have a radioactive facility of category 2, IRA - 1936 (IR-B/360/92). The authorization was granted on September 21, 1993 by the Department of Industry and Energy of the Government of Catalonia. It consists of a controlled access laboratory equipped with the necessary tools and equipment to carry on radioactive experimental procedures and supplied with the protective gear needed for the safe handling and storage of radioactive isotopes.

Cell Culture Facilities

The cell culture area of the IMIM provides all the infrastructure and equipment necessary to carry out cultures of mammalian cells, viruses and GMOs. In addition, its Scientific and Technical Services offer certain support services to users, such as media preparation, mycoplasma tests and cell line cryopreservation. The use of the cell culture rooms is restricted by electronic card access to registered users, who receive training in prevention, biosafety, and cell culture manipulation. An annual induction course on cell culture is also given as part of the IMIM educational programme.

Facilities and equipment

• 4 conventional culture rooms, with a total of 14 biological safety cabinets and 18 CO2 incubators. • One inverted microscope in each room, including 4 microscope imaging systems and 2 inverted fluorescence microscopes. • A biosafety level II laboratory approved by the Department of Agriculture, Food and

Rural Action (Generalitat de Catalunya), with 2 biological safety cabinets and 2 CO2 incubators.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 247 Facts and Figures · Core Facilities

Internal and External Services

MARGenomics

MARGenomics is an integrated translational platform that includes microarrays, qPCR and Next-Generation Sequencing technologies. This new platform was launched on 1 January 2019 and includes the Microarray Analysis Service (SAM) as well as offering wider services for biomedical research. The AffymetrixGeneChip® research and diagnostics platform offers an integrated service for cytogenetic, genomic, and transcriptomic studies. Arrays for human, mouse and other species are available.

Services

MARGenomics offers a wide range of services covering all phases of the genomic analysis process, from the initial phase of project advice, to final analysis of the data, validation of the results and expert support with their interpretation. The request for these services is coordinated by a Central Management Unit that supports application management procedures, the preparation of ethical/legal documents, sample or data transfer agreements (MTAs), and prepares budgets and billing. The request may include all phases of genomic analysis or just some of them. This means that it is also possible to initiate a request in the intermediate points of the service offered. • Advice on experiment design • Extraction of DNA and/or RNA from different types of samples (whole blood, frozen or FFPE tissue, etc.) • DNA/RNA quality analysis (quantification and integrity): - Quantification of DNA or RNA by fluorimetry and/or spectrophotometry - Analysis of DNA integrity by agarose gels and/or Bioanalyzer - Analysis of RNA integrity by Bioanalyzer • Real-time quantitative 4-PCR (qPCR) • Microarrays: - Expression (human, mouse, and other species) - Genomics

248 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

• Next Generation Sequencing (library preparation): - Whole Genome Sequencing - Exome Sequencing - RNA Sequencing - Small RNA sequencing - Panel Sequencing - ChIP Sequencing - Bisulphite Sequencing • Data analysis: - Sequence alignment - Variant calling and copy number analysis from genomic data - Identification of differentially expressed genes, alternative splicing and fusion genes in transcriptomic data - Study of small RNAs through microtranscriptome analysis - Identification of regions with peak protein-DNA interaction in chromatin immunoprecipitation sequencing experiments (ChIP-seq) - Identification of methylated DNA positions or regions in methylome data - Integration of data obtained from different “omic” platforms using specific methodology - Microarray analysis - qPCR analysis

Applications

• Discovery of biomarkers involved in biological processes • Gene expression profile studies • Detection of genes and pathways involved in diseases and pharmacological treatments • Pharmacogenomics and toxicogenomics studies • Alternative splicing detection • Dose-effect studies • Classification of samples based on gene signatures • Predictive models associated with genes • miRNA analysis • Microarray analysis of degraded samples (ex: FFPE) or/and low quantity samples (from 500pg of total RNA) • Genomic analysis • Integrative analysis

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 249 Facts and Figures · Core Facilities

Equipment

• Affymetrix Research Platform: GCS3000 with autoloader • Agilent Bioanalyzer 2100 • NanoDrop 2000 Spectrophotometer • GeneAmp PCR System 9700 (gold block) Thermocycler • Qubit Fluorometer • Proflex Thermocycler • 2720 GeneAmp PCR System • Qubit Fluorometer 2.0 and 4.0 • SimpliAmp Thermocycler • 2720 GeneAmp PCR System

Activity

Technical procedures Number Genomic arrays 98 Expression arrays 236 qPCR 95 Quality 120 Data analysis 19 RNA extraction 28 DNA extraction 639 Total 1,235

The 54 projects attended correspond to the following centers:

Centers Projects Percentage IMIM 20 35% PRBB (no IMIM) 4 7% External centers 33 58% Total 57 100%

The Microarray Analysis Service is subscribed to the European Microarray Quality Control Programme, organized by the CEQA (Cytogenic European Quality Assessment).

250 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

Publications

• García-Díez I, Hernández-Muñoz I, Hernández-Ruiz E, Nonell L, Puigdecanet E, Bódalo-Torruella M, Andrades E, Pujol RM, Toll A. Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients Genes Chromosome Canc 2019; 58(3): 164-174. FI: 2.94. Q2 • Hardy-Werbin M, Simoes da Rocha P, Arpí O, Taus A, Nonell L, Durán X, Villanueva X, Joseph-Pietras D, Nolan L, Danson S, Griffiths R, López-Botet M, Rovira A, Albanell J, Ottensmeier C, Arriola E. Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer OncoImmunology 2019; 8(6): e1593810. FI: 5.333. Q1.

Funded projects

• Regulación epigenética de la función inflamatoria del componente epitelial en la progresión metastática del carcinoma escamoso cutáneo (CEC) - Financing Institution: Fondo de Investigación Sanitaria (PI15/00236) - Period: from 2016 to 2019 - Principal investigators: Toll, Agustí; Hernández, Inmaculada - Research collaborator: Bódalo Torruella, Marta • Validación clínica y mecanismos de acción de las alteraciones moleculares con valor predictivo de progresión en el cáncer de próstata: algoritmo molecular de la carcinogénesis prostática - Financing Institution: Fondo de Investigación Sanitaria (PI15/00452) - Period: from 2016 to 2019 - Principal investigator: Lloreta, Josep - Research collaborator: Nonell Mazelón, Lara • Desarrollo y validación de un panel de secuenciación para translocaciones y mutaciones con relevancia clínica en neoplasias de células B maduras - Financing Institution: Fondo de Investigación Sanitaria (PI15/00437) - Period: from 2016 to 2020 - Principal investigator: Espinet, Blanca - Research collaborator: Nonell Mazelón, Lara; Puigdecanet Riubujent, Eulàlia • Micro-RNA as a novel biomarker of cardiovascular fibrosis in patients with degenerative aortic stenosis - Financing Institution: Marató (201519 10) - Period: from 2016 to 2019 - Principal investigator: Gómez Pérez, Miguel - Research collaborator: Nonell Mazelón, Lara

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 251 Facts and Figures · Core Facilities

• Ajuts per donar suport a les activitats dels grups de recerca (SGR) (12202) - Financing Institution: Grup de Recerca Traslacional en Neoplàsies Hematològiques (GRETNHE) SGR - Period: from 2017 to 2020 - Principal investigator: Espinet, Blanca - Research collaborator: Nonell Mazelón, Lara; Puigdecanet Riubujent, Eulàlia • Influencia de las concentraciones de compuestos tóxicos persistentes sobre la mortalidad, la incidencia de trastornos crónicos y la expresión de miARN en población general - Financing Institution: Fondo de Investigación Sanitaria (PI17/00088) - Period: from 2018 to 2020 - Principal investigator: Porta, Miquel - Research collaborator: Bódalo Torruella, Marta • Alteraciones epigenéticas generadas por exposición prenatal al alcohol en pacientes con SAF (síndrome alcohol fetal). Antioxidante epigalocatequina (EGCG) como herramienta terapéutica - Financing Institution: Fondo de Investigación Sanitaria (PI16/00566) - Period from 2017 to 2019 - Principal investigator: García, Óscar - Research collaborator: Bódalo Torruella, Marta • Red de salud maternoinfantil y del desarrollo - Financing Institution: RETIC (RD16/0022/0002) - Period: from 2017 to 2021 - Principal investigator: García, Óscar - Research collaborator: Bódalo Torruella, Marta

Fundings

• Grants for Thechnical Support Personnel Contracts. MINECO (PTA2014-09119-I). 2015-2019.

BIOBANK MARBiobanc

The biobank of the Parc de Salut Mar (MARBiobanc) is a public, non-for-profit facility which stores various collections of biological samples available to the whole scientific community. It is organized as a technical unit with regards to quality, order and destination. It has restricted access facilities which are equipped with the security control mechanisms necessary to ensure the correct storage of the biological samples, their

252 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

confidentiality and their traceability in accordance with all the Spanish ethical and legal regulations. The Biobank Service is certified by AENOR to ISO 9001:2015.

Available human biospecimen collections

• DNA bank for cardiovascular diseases • Cerebral infarction (ictus) sample bank • FORTIAM, acute myocardial infarction sample collection • DNA bank for oncological diseases • Bank of samples from influenza A (H1N1) patients • Bank of lung disease samples (Lung Biobank Platform) • Hematological malignancies bank • Left over diagnose sample bank • Cryopreserved tumour bank • Collection Alzheimer and families (Alfa Study) • ERyME: Sample collection from patients with rheumatic or muscle-skeletal disease • GLOSEN: Glomerular diseases sample collection • Colorectal cancer Two new collections were incorporated: • Plasma and serum samples (liquid biopsy) collection from patients with solid and haematological neoplasms • Tumoroids collection from human colorectal cancer

Research line collections

• Nine new research line collections have been added to the Biobank facility to be managed under biobank standards.

Activity

Parameter 2019 Number of requests* 135 Samples approved 7,723

* 38 clinical assays and 97 research projects

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 253 Facts and Figures · Core Facilities

There were 47 other services including general assessment in legal and ethical aspects, new collections, National Register of Biobancs (ISCIII), informed consent (IC), revision of documents, etc. It is important to highlight that in 2019 the biobank obtained 6,514 new donors from patients of the hospital. These donations allow the biobank to transfer their diagnostic/ treatment left-over samples to research projects after the approval of biobank external scientific and ethics committees. The biobank is subscribed to the Biobanks European Quality Control Program, organized by the IBBL (Integrated Biobank of Luxembourg).

Fundings

• Concession of the Biobanks Platform. Instituto de Salud Carlos III/FEDER (PT17/0015/0011). Period: 2018-2020.

Dissemination to society

• 14 MARBiobanc dissemination sessions, including Open Day and student visits. • MARBiobanc Website. This website has been operational since June 2016. The website received a total of 1,732 visits from January to December 2019, with 734 new users. The pages most visited are in the Spanish language, followed by English. • MARBiobanc has also available an Instagram channel, and Twitter and LinkedIn profiles.

New Informed Consent (IC) adapted to personal data protection regulation

The new IC models have been developed and distributed, which include Regulation (EU) 2016/679 of the European Parliament and of the Council, and Organic Law 3/2018, on the protection of personal data and the guarantee of digital rights in 2019.

Publications 2019 with MARBiobanc samples

A total of 15 scientific publications have been done with samples obtained from MARBiobanc.

Microdissector Laser (microscopy area)

The ArcturusXT™ microdissection system offers a combination of infrared (IR) laser capture using standard slides, or a combination of both infrared and ultraviolet (IR and UV) laser, using polyethylene naphthalate (PEN) membrane slides laser enabled. The instrument has a proprietary combination of a gentle IR laser and a powerful UV laser that work in conjunction to efficiently isolate cells without changing morphology or integrity of the biological content. The IR laser helps to capture the cells of interest, and the UV laser microdissects the captured cells. This is done without affecting the

254 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

morphology of the cells, and allows for visual inspection of the remaining specimen to help ensure the quality of the sample collected. A wide-slide stage format is available for neurobiology researchers working with very large sections of brain tissue. The petri dish stage insert has opened the door for live-cell microdissection applications such as stem cell research and other rare-cell isolations. The LCM technique can be used on formalin-fixed, paraffin-embedded (FFPE) sections, allowing the use of archival pathological material. In addition, frozen sections of tissue and cytological specimens are also suitable for laser microdissection. The technique causes no apparent alteration to the morphology of the chosen cells, which can be directly visualized after microdissection.

Key features

• Dual laser system-enables a wide range of applications ranging from single-cell isolation to large biopsy extractions. • IR laser capture microdissection preserves morphology of isolated samples and integrity of biological material for downstream applications. • Software enables rapid isolation of specific cells in five simple steps, provides quality control feature that allows users to visualize collected sample. • Flexible sample prep-wide range of slide types and sample preparation formats supported.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 255 Facts and Figures · Core Facilities

Other Services

Animal Facility (PRBB)

The PRBB animal facility is one of the most complex and robotized installations of its kind in Europe and is fully accredited by AAALAC, the International Association for Assessment and Accreditation of Laboratory Animal Care. This is the maximum international certification and implies an acknowledgement of the quality of the operation of the facility which translates into better practices and research results. The main animal models are zebrafish and mice, but it is also possible to use rats, hamsters, rabbits, frogs and axolots. The animal facility covers 4,500 m2 with six independent units, which are connected and run under a single management: • The aquatic animal area (zebrafish and xenopus) • The specific pathogen germ free (SPF) barrier zone for rodents, with modern auto- ventilated microisolators and three support laboratories • A transgenesis area with large laboratories (250 m2) for the production of genetically modified mice • The experimental area with laboratories, surgery rooms and an irradiator • The quarantine area with its own access changing rooms and embryonic transfer re- derivation laboratory • A conventional animal facility, located at an adjacent building, which is connected via a tunnel with the PRBB, and has a surface area of 1,300 m2, mainly for studies with animal models in neuropharmacology and immunology The number of Animal Facility users in 2019 was 418. The Ethical Committee for Animal Research (in USA, IACUC-Institutional Animal Care and Use Committee) conducted 9 meetings where 44 projects were evaluated (6 from IMIM). These projects include 92 experimental procedures (16 from IMIM).

Clinical Research Unit (IMIM)

The Clinical Research Unit (CRU) has 12 beds and capacity to run different studies at the same time. The equipment is especially well suited for Phase I clinical trials in drug development, for bioequivalence studies, for nutritional interventions or

256 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Core Facilities

for the evaluation of nutraceuticals. Studies are performed in accordance with the Good Clinical Practice (GCP) standards. The CRU is accredited by the Government of Catalonia for the performance of Phase I studies. The Drug Research Ethical Committee (CEIm-Parc de Salut Mar) evaluates the study protocols in accordance with Spanish and European regulations. The CEIm has two regular meetings every month. It is accredited by the Government of Catalonia and the Spanish Agency of Medicines and Medical Products.

Available services

• Phase I and Phase II clinical trials • Evaluation of the abuse potential of new drugs • Psychopharmacology and behavioral pharmacology clinical studies • Methodological advice for clinical trial protocols • Nutritional interventions and evaluation of nutraceuticals • Pharmacokinetic studies - Bioavailability, including bioequivalence studies of generic drugs - Metabolism and identification of metabolites

Health-Related Quality of Life Questionnaires

BiblioPRO is a virtual library of Quality of Life Questionnaires and other Patient Reported Outcomes (PROs) in Spanish with free and open access. The mission of our project is to promote the adequate use of HRQL instruments in Spanish among researchers, clinicians and health management, by providing exhaustive online information, evidence-based evaluations, and specialized training in this area. The library currently holds information on 2,027 questionnaires and is updated periodically. BiblioPRO is a CIBER in Epidemiology and Public Health research and knowledge transfer support action, initiated, directed and coordinated by the Health Services Research Unit of the IMIM, with the IMIM Foundation support.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 257

Facts and Figures

RESEARCH ACTIVITY

> Scientific Publications > Research Grants and Transfer of Results > Clinical Guidelines > Committees > Scientific Advisory Board

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 259 Facts and Figures · Research Activity

Scientific Publications

Number of articles and Normalised Impact

Normalised impact

780 3.5

760 2.5

2 740 1.5

1 720

0.5

700 0 2014 2015 2016 2017 2018 2019

Number of articles: Sum of original and revised articles. Normalised Impact (NI): Index of citations received in relation to the worldwide average within its category or scientific sphere. Thus, considering 1 as the worldwide average an NI of 0.8 means that it has received 20% fewer citations than the world average, whereas an NI of 1.3 means it has received some 30% more citations than the world average.

Source: Web of Science consulted in March 2020.

260 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

Key indicators

80%

60%

1st Q

40% 1st D

Excellence

20%

0% 2014 2015 2016 2017 2018 2019

1st Q: Percentage of articles published in journals in the first quartile of their category. 1st D: Percentage of articles published in journals in the first decile of their category. Excellence: Percentage of articles among the 10% most cited in their category. International collaboration: Percentage of articles published in collaboration with institutions from other countries. We do not have data available for the years 2014 and 2015.

Source: Web of Science consulted in March 2020 and IMIM data.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 261 Facts and Figures · Research Activity

Leadership indicators

80%

60%

Leadership

40% Excellence with leadership

20%

0% 2014 2015 2016 2017 2018 2019

Leadership: Percentage of articles with corresponding author belonging to the institution. Excellence with Leadership: Percentage of articles with corresponding author belonging to the institution that are among the 10% most cited in their category.

Source: Web of Science consulted in March 2020 and IMIM data.

Open Access

50%

40%

30%

20% Open Access: Percentage of articles published in open-access journals and/or incorporated into the institutional repository. 10% For the year 2014 we do not have data available and 2019 data are provisional.

Source: IMIM data. 0% 2014 2015 2016 2017 2018 2019

262 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

Distribution by areas of knowledge

Note: An article can be counted in more than one category.

Source: Web of Science consulted in March 2020.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 263 Facts and Figures · Research Activity

Research Grants and Transfer of Results

During 2019, the IMIM Foundation presented a total of 412 grant applications for research. In relation to contracts with private enterprises, it should be highlighted that 99 contracts were signed for the provision of services, 43 contracts of patronage, and 142 contracts for the conducting of clinical trials for a global total amount of over nine million euros. Another 60 contracts were signed as coordinators of trails with other centres.

Grants for Projects

With respect to the competitive calls from the State Agency for Research, within the framework of the modalities of Challenges in Research and Generation of Knowledge, 5 proposals were presented. Twenty-four projects were obtained from the 50 presented for the call for Health Research Projects made by the Carlos III Health Institute (Instituto de Salud Carlos III-ISCIII), which means a success rate of 48%, a percentage higher than the Spanish average (35%). In 2019, the Government of Catalonia, from its Ministry of Health, resolved the third call for research grants in Health within the Strategic Plan in Health Research and Innovation (PERIS) and two proposals were obtained for Intensifications of nursing staff and a proposal for Intensifications for medical staff. A sub-project at the centre was approved in the La Caixa Health Research call. As for international projects, three H2020 projects were approved, despite it being necessary to highlight that the number of requests continues rising, reaching 12 proposals.

Staff Grants

Two pre-doctoral candidates were incorporated through AGAUR subsidies for the hiring of novice research personnel (FI). With respect to the human resources calls of the ISCIII, the results were exceptional. The personnel funded were: 3 intensifications, 4 post-residency Río Hortega grants, 3 Sara Borrell post-doctoral grants, 5 Pre-doctoral Training Grants in health research (PFIS), 2 Miguel Servet researcher contracts and 2 Juan Rodés Grants. In relation to grants self-funded by the Institution, three Jordi Gras grants were awarded for training in research of doctors completing their residency in 2019. The grant for

264 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

training at research centres abroad for specialist medical staff of the Parc de Salut Mar was called and awarded. Below are the breakdowns of the grants achieved by areas, programmes, and funders.

Grants awarded in the year 2019 by fields

Other grants

Human Resources 33 71 Projects

Grants awarded in the year 2019 by research programme

Hospital

Cancer 5 Neurosciences 15 20

10 Epidemiology and Public Health 4 17

Projects for funders of the national sphere in force in 2019

AEI - Spanish State Research Agency (15) La Marató (6)

Spanish Ministry of Health (2)

La Caixa (3) Catalan Ministry of Health (16) Catalan Government (3)

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 265 Facts and Figures · Research Activity

Projects for funders in the international sphere in force in 2019

EU 11 15

Transfer of Results

Activity in transferring research results continues to increase, with 5 European patents presented, of which 3 were in co-ownership with other centres. The Innovation Clubs initiative was maintained. This is an interdisciplinary meeting space that, once a month, brings together institution staff interested in innovation with the aim of learning about new experiences and seeking synergies. The subjects proposed were: • 3D innovation at the Hospital del Mar. • Photonic technologies in the healthcare sector. • Transforming the digital experience: Chatbots in health. • Extraction of information through text mining: application to medical histories and social media networks. • Artificial intelligence: Everything a doctor should know. Since the summer, an Innovation Bulletin has been published bimonthly, as a tool for technological surveillance and to raise the visibility of initiatives carried out within the centre. The Board of Trustees approved the creation of a spin-off company, based on the DISGENET platform, on which work has been done over the course of the year. The researchers participating in the company are Ferran Sanz, Laura Furlong and Janet Piñero, from the Research Programme in Biomedical Informatics. The company will be working on added-value data mining technologies. A transfer agreement was signed in relation to some software and 2 more were signed for the use of the dual diagnosis screening interview (ECDD) digital questionnaire. Furthermore, 4 students from the Open University of Catalonia (UOC) spent time at the centre as part of their Final Projects for their IT, Multimedia and Telecommunications

266 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

Studies (EIMT), thanks to the collaboration agreement established with the Open University of Catalonia (UOC) so that IMIM researchers can co-direct proposals for Final Projects in IT, Multimedia and Telecommunications Studies (EIMT) with application to the field of research and health. Our innovation funnel now contains: 17 new ideas, 3 innovations at analysis phase, 19 in development and 2 at transfer phase. The Parc de Salut Mar (PSMAR) has incorporated a Director of Innovation and Digital Transformation who has determined that the priority lines in this sphere are as follows:

PROCESSES DIGITALISATION 1 DIGITAL PATIENT EXPERIENCE 2 PRIORITY DATA-DRIVEN ORGANISATION 3 LINES TALENT DEVELOPMENT 4 HOSPITAL 2030 5

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 267 Facts and Figures · Research Activity

Clinical Guidelines

• Ascaso JF, Civeira F, Guijarro C, López-Miranda J, Masana L, Mostaza JM, Pedro-Botet J, Pintó X, Valdivielso P. Indicaciones de los inhibidores de PCSK9 en la práctica clínica. Recomendaciones de la Sociedad Española de Arteriosclerosis (SEA), 2019. Clin Invest Arterioscl 2019; 31(3): 128-139. • Balato A, Raimondo A, Arenberger P, Bruze M, Czarnecka- Operacz M, Johanssen JD, Gonçalo M, Ranki A, Uter W, Wilkinson M, Ayala F, John SM, Giménez-Arnau AM, Gollnick H. The role of the dermatologist in the immune-mediated/ allergic diseases - position statement of the EADV task force on contact dermatitis, EADV task force on occupational skin diseases, UEMS-EBDV subcommission allergology and European Dermatology Forum. J Eur Acad Dermatol Venereol 2019; 33(8): 1459-1464. • Bataller R, Cabezas J, Aller R, Ventura-Cots M, Abad J, Albillos A, Altamirano J, Arias- Loste MT, Bañares R, Caballería J, Caballería L, Carrión JA, et al. Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. Gastroenterol Hepatol 2019; 42(10): 657-676. • Bollerslev J, Schalin-Jantti C, Rejnmark L, Siggelkow H, Morreau H, Thakker RV, Sitges- Serra A, Cetani F, Marcocci C, on behalf of the PARAT Workshop Group. Management of endocrine disease: Unmet therapeutic, educational and scientific needs in parathyroid disorders. Eur J Endocrinol 2019; 181(3): P1-P19. • Bousquet J, Bedbrook A, Czarlewski W, Onorato GL, Arnavielhe S, Laune D, Mathieu- Dupas E, Fonseca J, Costa E, Lourenço O, et al (Antó JM), The MASK study group. Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma. Clin Transl Allergy 2019; 9: 16. • Caballeria L, Augustin S, Broquetas T, Morillas RM, Vergara M, Virolés S, Hernández MR, Serra I, Goday A, Vila L, Siso-Almirall A, Solans R, Fernández-Real JM, Carrión JA, Graupera I, Ginès P. Recomendaciones para la detección, diagnóstico y seguimiento de los pacientes con enfermedad por hígado graso no alcohólico en atención primaria y hospitalaria. Med Clin (Barc) 2019; 153(4): 169-177. • Chahla J, Murray IR, Robinson J, Lagae K, Margheritini F, Fritsch B, Leyes M, Barenius B, Pujol N, Engebretsen L, Lind M, Cohen M, Maestu R, Getgood A, Ferrer G, Villascusa S, Uchida S, Levy BA, Von Bormann R, Brown C, Menetrey J, Hantes M, Lording T, Samuelsson K, Frosch KH, Monllau JC, Parker D, LaPrade RF, Gelber PE. Posterolateral corner of the knee: an expert consensus statement on diagnosis, classification, treatment, and rehabilitation. Knee Surg Sports Traumatol Arthrosc 2019; 27(8): 2520-2529. • Cossarizza A, Chang HD, Radbruch A, Acs A, Adam D, Adam-Klages S, Agace WW, Aghaeepour N, Akdis M, Allez M, et al (López-Botet M). Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur J Immunol 2019; 49(10): 1457-1973.

268 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

• Font A, Luque R, Villa JC, Domènech M, Vázquez S, Gallardo E, Virizuela JA, Beato C, Morales-Barrera R, Gelabert-Mas A, Macià S, Puente J, Rubio G, Maldonado X, Pérez- Valderrama B, Pinto A, Fernández Calvo, Grande E, Garde-Noguera J, Fernández-Parra E, Arranz JÁ. The Challenge of Managing Bladder Cancer and Upper Tract Urothelial Carcinoma: A Review with Treatment Recommendations from the Spanish Oncology Genitourinary Group (SOGUG). Target Oncol 2019; 14(1): 15-32. • Grávalos C, Sanmartín O, Gúrpide A, España A, Majem M, Suh Oh, Aragón I, Segura S, Beato C, Botella R. Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology. Clin Transl Oncol 2019; 21(5): 556-571. • Gutiérrez-Gutiérrez G, Díaz-Manera J, Almendrote M, Azriel S, Bárcena JE, Cabezudo P, Camacho A, Casanova C, Cobo AM, Díaz-Guardiola P, et al (Rubio MA). Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert. Med Clin (Barc) 2019; 153(2): 82.e1-82.e17. • Hiligsmann M, Cornelissen D, Vrijens B, Abrahamsen B, Al-Daghri N, Biver E, Brandi ML, Bruyère O, Burlet N, Cooper C, Cortet B, Dennison E, Díez-Pérez A, et al. Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF). Osteoporosis Int 2019; 30(11): 2155-2165. • Horwich A, Babjuk M, Bellmunt J, Bruins HM, Reijke TM, Santis M, Gillessen S, James N, Maclennan S, Palou J, et al. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi- stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees. Ann Oncol 2019; 30(11): 1697-1727. • Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dres M, Dubé BP, Fauroux B, Gea J, Guenette JA, et al. ERS Statement on Respiratory Muscle Testing at Rest and during Exercise. Eur Respir J 2019; 53(6): 1801214. • Mostaza JM, Pintó X, Armario P, Masana L, Ascaso JF, Valdivielso P, members of the Sociedad Española de Arteriosclerosis (Pedro-Botet J). Standards for global cardiovascular risk management arteriosclerosis. Clin Invest Arterioscl 2019; 31 (Suppl 1): 1-43. • Sanmartín O, Beato C, Suh-Oh HJ, Aragón I, España A, Majem M, Segura S, Gúrpide A, Botella R, Grávalos C. Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica. Actas Dermosifiliograf 2019; 110(6): 448-459. • Weisshaar E, Szepietowski JC, Dalgard FJ, Garcovich S, Gieler U, Giménez-Arnau AM, Lambert J, Leslie T, Mettang T, Misery L, Savk E, Streit M, Tschachler E, Wallengren J, Ständer S. European S2k Guideline on Chronic Pruritus. Acta Derm-Venereol 2019; 99(5): 469-506.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 269 Facts and Figures · Research Activity

Committees

Drug Research Ethical Committee

The Drug Research Ethical Committee (CEIm) of Parc de Salut Mar was created and accredited on November 11, 1993 by the General Management of Health Resources of the Autonomous Government of Catalonia, in accordance with the “Ordinance dated October 26, 1992”. Subsequently we were reaccredited on 19 December 2008 via the Order dated 24 October, 2006; and again on 27 October 2014. Accredited as a CEIm on February 7, 2018. The principal duties of CEIm-Parc de Salut Mar, which are regulated by current legislation and approved by the Administrative Council of Parc de Salut Mar, are as follows: • To evaluate the suitability of study protocols with regard to the objectives of studies, their scientific efficiency and the justification of the foreseeable risks weighed against the expected benefits for research subjects and society (riskbenefit ratio). • To evaluate the suitability of the research team with regards to its experience and capacity to carry out the study. • Clinical care requirements and commitments previously made to other research protocols are taken into consideration. • To evaluate written study information to be given to participating research subjects (or to their legal representatives). • To evaluate the procedure by which such information will be given and the type of consent to be obtained. • To check the compensation and treatment being offered to research subjects in case of injury or death resulting from the study and to verify liability insurance to cover the funding agency, researchers, collaborators and the individual responsible at the center where the research is to be carried out. • To be aware of and to evaluate the compensation to the study researchers and compensation to the subjects for their participation in the study. • To monitor studies from the time of their inception and to follow them up until completion of the final report.

270 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

List of studies evaluated in 2019, classified by type

Clinical trials with drugs 29 Food and supplement clinical trials 0 Clinical testing of cosmetics and personal care products 0 Clinical trials for medical devices 7 Post-authorisation studies 48 Observational studies 49 Research projects 333 Genetics 1 Other (academics…) 13 Total 480

Committee for Research Integrity and Good Scientific Practice

The Committee for Research Integrity (CRI) of the IMIM was constituted by the Scientific Management of the institution to act at the complete service of researchers and the scientific community, with the interest of giving support to the quality of research and contributing to its integrity. Its specific functions are: • To provide information and raise awareness with regard to events, necessities and orientations related to research integrity and good scientific practices in biomedical research. • To promote and ensure that IMIM researchers and research support personnel receive appropriate training in best scientific practices to guarantee good scientific practices and integrity in the research developed at the IMIM. • To implement procedures and investigate potential cases of research integrity misconduct. In relation to the functions mentioned above, the Committee will guarantee, by all means, its own managerial diligence, independence of action, anonymity, and confidentiality in the processing of personal data, solvency of the information generated, impartiality in the deliberation process and equity of resolutions as well as possible allegations.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 271 Facts and Figures · Research Activity

This Committee will form part and will work in alignment with the CRI of the Barcelona Biomedical Research Park (PRBB). The functions of the CRI of the PRBB are: • To supervise the general, constant, and complete fulfilment of the guidelines of the Code of Good Scientific Practice at the PRBB’s centers. • To act as an arbitration body for doubts or disputes that may arise in relation to research integrity matters. Its decisions are binding for those researchers submitting their disputes to the CIR. • To provide information and continuously raise awareness with regard to events, necessities and orientations related to the ethical and deontological aspects of biomedical research. The Committee has the commitment to request from the Governing Bodies of the Centers those resources and measures that will contribute to the development of this function. • To be receptive to new problems related to research integrity, to propose their discussion to our institutions and, consequently, to update the Code of Good Scientific Practice as needed.

Ethical Committee for Animal Research

The PRBB has an Ethical Committee for Animal Research (CEEA-PRBB) which evaluates project procedures using experimental animals. It takes into account the appropriateness of the procedure in relation to the objectives of the study, the possibility of reaching valid conclusions with the fewest animals, the effect on the animals not being disproportionate to the potential benefits of the research, and, in short, the avoidance of unnecessary suffering, as well as considering the possibility of alternative methods to the use of animals. That is the internationally accepted 3R rule (Reduction, Refinement and Replacement). The Ethical Committee for Animal Research (in USA, IACUC- Institutional Animal Care and Use Committee) conducted 9 meetings where 51 projects were evaluated. These projects include 80 experimental procedures.

Procedures

Center n % PRBB 3 3.75% UPF 26 32.50% CRG 10 12.50% IMIM 35 43.75% External centers 6 7.50% Total 80 100%

272 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

Projects

Center n % PRBB 2 3.92% UPF 16 31.37% CRG 9 17.65% IMIM 18 35.30% External centers 6 11.76% Total 51 100%

During the meetings scientific articles and new ways of controlling and improving animal welfare to adapt to the new legislation on animal experimentation have been discussed. Also comments, recommendations or amendments done by the Government of Catalonia’s Animal Experimentation Ethics Committee (CEEA) were included in each meeting. The CEEA also carried out their traditional inspection of the animal facility, which is a quality requirement recommended both by the AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care International) and current legislation.

PRBB Animal Facility Users’ Committee

The Animal Facility Users’ Committee at the Barcelona Biomedical Research Park (CUA- PRBB) is an advisory committee external to the animal facility that reports directly to the PRBB management. The committee’s main objective is as a forum to provide information and debate the most important issues affecting the animal facility. Its functions are: • To remain informed and be aware of the content of animal facility’s annual report. • To raise any problems identified in the overall functioning of the animal facility as well as to discuss and propose new solutions. • To discuss processes and operating procedures at the animal facility and make suggestions as to how to improve them. • To propose functional or procedural solutions for extraordinary action within the animal facility that may involve modifications from the normal routine, such as building work, repairs, supply cuts, reviews, extraordinary maintenance, etc. • To make suggestions for improving the facilities, including the purchase or replacement of equipment, and to prioritize these purchases.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 273 Facts and Figures · Research Activity

• To take part, when appropriate, in the preparation of applications for equipment grants or funds for provisioning the animal facility. • To participate in the development of satisfaction surveys. • To collaborate in the evaluation and assessment of these surveys. The Animal Facility Users’ Committee (CUA-PRBB) conducted two meetings during 2019 in order to address the various issues affecting the functioning of the animal facility, to solve problems and consider proposals from researchers in the field of animal experimentation.

Barcelona Biomedical Research Park Biosafety Committee

The Barcelona Biomedical Research Park Biosafety Committee (CBS-PRBB) was set up with the aim of regulating and supervising the activities using GMOs (Genetically Modified Organisms) that take place around the PRBB, as set out in Law 9/2003 of 25 April, establishing the legal regime for the confined use, voluntary release and commercialization of genetically modified organisms, and considering the general norms for their development and implementation (Royal Decree 178 / 5004, 30 January). The main objective of the CBS-PRBB is the biosafety evaluation of scientific projects using GMO, biological and chemical agents with a complex or important biological effect according to current biosafety legislation. The Biosafety Committee (CBS-PRBB) held two meetings, evaluated 18 projects and received 3 queries during 2019. Among other activities, it collaborated with the Inter- institutional Commission on Prevention of Occupational Risks (CIPRL) in reviewing a document on the transport of biological samples in order to implement this throughout the PRBB.

Inter-institutional Commission on Prevention of Occupational Risks at the Barcelona Biomedical Research Park (CIPRL-PRBB)

The Inter-institutional Commission on Prevention of Occupational Risks at the Barcelona Biomedical Research Park (CIPRL-PRBB) was created in application of Article 24 of Law 31/1995 of 8 November, on the Prevention of Occupational Risks, in matters of the coordination of business activities to channel the exchange of preventive information between the companies involved and the joint establishment of preventive measures, procedures and action protocols at the Barcelona Biomedical Research Park. Its purpose is to give support to the management by the health and safety of the personnel existing at the building. This Commission is the legacy of the Inter-institutional Prevention Group for the Coordination of Preventive Activity at the Barcelona Biomedical Research Park (GPIPRBB) which was created on 8 January 2008 by specialists in prevention.

274 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Research Activity

The tasks performed are diverse, and include: • Information campaigns featuring the “Previ” mascot as a joint image for the Prevention of Occupational Risks in the building. • Joint publications in different journals, participations with oral presentations and posters at congresses in the prevention sphere, publication of manuals on preventive information in the sphere of biomedical research, participation in the PRBB Open Day with a range of workshops, etc. • Awards: Ignasi Fina Occupational Health Award 2010 (April 2010), Occupational Health Advisory Council of Barcelona City Council; runner-up at the 6th Atlante awards, in the modality of large company and the category of initiatives for awareness-raising, information and/or training (November 2012), Foment del Treball Nacional, and Pompeu Fabra University Award 2019 (April 2019), for the integration of safety and health in university activity, in the form of Contribution to the implementation of occupational risk prevention in the management system with the 2018-2019 campaign “La prevenció és cosa de tots”. During 2019, the CIPRL-PRBB held five coordination meetings, with the aim of promoting coordination between all the institutions resident in the building, that participate in biomedical research activity. The most prominent activities were: • ORP Congress 2019, held in June 2019, where we presented two papers: “Prevention is a matter for everyone, beginning with you” and “Procedure for transferring biological samples”. • Monitoring of the Awareness-raising and Advocacy Campaign 2018-2019 with the activities “Epidemiology of Centres” and “Photography Contest”. • Revision of the document “Basic Rules for the Transfer of Biological Samples”. Each Meeting also includes comments and recommendations to be taken into account and exchanges regarding everyday issues: emergencies, accidents, incidents, etc. The Commission also liaises with the PRBB Biosecurity Committee (CBS) to develop a joint focus on the different issues and with the Communications departments of the PRBB and the different companies, to provide each other with support in the information campaign implemented.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 275 Facts and Figures · Research Activity

Scientific Advisory Board

President

Joaquín Arribas, PhD Vall d’Hebron Institute of Oncology (VHIO) (Barcelona, Spain)

Members

Celso Arango MD, PhD Lucca Gianni, MD Hospital General Universitario Gregorio Ospedale San Raffaele (Milan, Italy) Marañón Director CIBERSAM (Madrid, Spain) Francisco Fernández Avilés, MD, PhD Hospital General Universitario Gregorio Søren Brunak, PhD Marañón (Madrid, Spain) Center for Biological Sequence Analysis, Technical María Luisa Toribio, MD, PhD University of Denmark (Lyngby, Denmark) Centro de Biología Molecular Severo Ochoa Fernando Rodríguez de Fonseca, PhD Universidad Autónoma de Madrid Hospital Regional de Málaga. IBIMA. (Madrid, Spain) Director RTA (Spain) Marina Pollán, MD Joaquín Dopazo, PhD National Center for Epidemiology Fundación Pública Andaluza Progreso y Instituto de Salud Carlos III (Madrid, Salud. Junta de Andalucía (Sevilla, Spain) Spain)

276 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY

278 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures

MANAGEMENT

> Management Structure > Income > Human Resources > Quality > Communication > Governing Bodies

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 279 Facts and Figures · Management

Management Structure

The mission of the Management Division is to provide administrative and logistic support to the researchers at IMIM.

Director of Management Joaquim Bellmunt Molins (until 28/08/2019), Jordi Martínez Roldán (since 04/10/2019; temporary designation)

Manager Andreu Fort Robert

Management Secretary Pilar Sánchez Macías

Accounts Marta Mestres Mestres (head of service), Ana Godall Peralta, Rosa Gras López, Noemí Morín Rodríguez, David Palomeque Reina (since 23/07/2019)

Communication/Reception Rosa Manaut Dueñas (head of service), Marta Calsina Freixas (communication), M. Inmaculada Colom Mesquida (reception), M. Carmen de la Bella Toledano (reception)

280 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

General Services Rosabel Marrugat Lacosta (since 29/11/2019) (head of service), Patxi Fernández Navarro (until Sept 2019; partial retirement)

Health and Safety Sandra Vial Mora (head of service)

Human Resources Maria Merino Tapia (since 15/07/2019) (head of service), Balbina Ugena Villalobos (until 28/08/2019), Anna Maria Adell Vallhonesta, Verónica Alonso Corbatón (since 24/04/2019), Georgiana Anghelache, José Maria Contreras Agudo (since 02/09/2019), Miriam Martínez Romero (until 30/04/2019), Laia Rabal de Andrés, Diana Sebastián Guillart

IT Resources Joan Marc Carbó (head of service), Xavier Durán Sans, Pau Espinàs Romero, Max Fusté Valls, Iván Martínez Campos, Jonathan Moral Cortés (since 02/09/2019)

Legal Consultancy and Contracting Aida Pérez González, Vanessa Puig Suárez (until 30/06/2019), Marta Rabal de Andrés

Purchasing Concepción León Pérez (head of service), M. Aranzazu Bernal Ybarra, Laura Erruz Peregrina, Laia Orpinell Ros

Quality Xavier Palazón Vilarrasa (until 28/08/2019), Montserrat Salguero Pulido

Research Support Marta López Otero (head of service), Carol Barnwell, Mercedes Bayo Romero, Marta del Olmo Zurriaga, Teresa Macià Úbeda, Sergio Sanz Ruiz, Anaí Villanueva Delgado

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 281 Facts and Figures · Management

Income

Income in the year 2019 increased generally; emphasis should be placed on the increase in international grants for the neurosciences programme and the inflammation programme (among others, the Alzheimer Association, WADA and the Cancer Research Institute) and from the European Union for the bioinformatics and inflammations programme, as well as grants from the Carlos III Institute for the neurosciences and inflammation programme. In contrast the grants awarded under the PERIS (Health Research and Innovation Strategic Plan) have suffered a decline. With respect to other income, it is important to highlight the increase in invoiced revenue from clinical trials (mainly in the cancer programme) and services contracts (mainly in the neurosciences and inflammation programmes).

External funding

Total external funding 2019 2018 Competitive Grants 8,495.23 46.73% 6,852.93 43.48% European Commission 727.13 4.00% 250.14 1.59% International 1,013.45 5.57% 362.38 2.30% National 6,754.65 37.15% 6,240.41 39.59% Other External Funding 9,685.79 53.27% 8,909.31 56.52% Research services 6,980.85 38.40% 6,332.75 40.18% Other services 1,893.38 10.41% 1,866.03 11.84% Charity 811.56 4.46% 710.53 4.51% Total 18,181.02 100% 15,762.24 100%

282 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Sources of funding

Competitive 8,495,226.16 European Union 727,126.16 Other international grants 1,013,446.11 National grants 5,472,129.84 Public bodies of the Generalitat 1,282,524.05 Non-competitive 9,685,799.18 Clinical trials 4,167,120.70 Research contracts 2,813,734.07 Donations 811,562.73 Technology transfer 269,142.25 Analytics and Quality Control 1,386,312.32 Courses and congresses 39,840.25 Others 198,086.86 Trustees contribution (Generalitat de Catalunya) 3,100,000.00 TOTAL 21,281,025.34

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 283 Facts and Figures · Management

Profit and loss account

2019 2018 1. Revenue by activities 18,998,359.71 18,793,826.47 a) Provision of services 8,447,293.12 7,977,728.72 b) Official activities for grants 9,981,383.88 9,678,807.77 c) Donations and other revenue for activities 728,365.00 1,246,000.05 d) Grant reimbursements -158,682.29 -108,710.07 2. Procurements -2,623,896.17 -2,734,525.01 a) Consumption of raw materials and other -1,893,817.95 -2,047,554.81 consumables b) Works carried out by other organisations -730,078.22 -686,970.20 5. Personnel expenses -10,033,934.16 -9,320,143.75 a) Wages, salaries and similar -7,719,355.52 -7,228,298.54 b) Social charges -2,314,578.64 -2,091,845.21 6. Other operating expenses -6,346,870.32 -6,814,343.32 a) External services -6,388,751.81 -6,716,534.12 a.1) Research and development -1,615,823.12 -1,964,753.14 a.1) Rentals and fees -2,327,977.89 -2,210,814.82 a.2) Repairs and conservation -312,134.55 -340,447.88 a.3) Independent professional services -888,795.24 -898,340.47 a.5) Insurance premiums -56,817.96 -40,842.76 a.6) Banking services -3,451.84 -3,249.56 a.7) Advertising, publicity and public relations -54,316.17 -75,506.10 a.8) Supplies -273,730.91 -262,671.51 a.9) Other services -855,704.13 -919,907.88 b) Taxes -7,143.70 -4,437.76 c) Losses, deterioration and variation of 49,025.19 -93,371.44 provisions 7. Depreciation of fixed assets -564,734.48 548,155.51

284 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

2019 2018 8. Grants, donations and legacies transferred to 564,734.48 -548,155.51 the result 10. Impairment and result of disposal of fixed -217.68 0.00 assets a) Impairment and losses -217.68 0.00 13. Other results 7,813.06 0.00 I) OPERATING RESULT 1,254.44 -75,185.61 14. Financial income 66,379.03 8,739.48 b) From negotiable securities and other financial 60,329.97 765.00 instruments b.1) Other financial instruments 16,271.64 0,00 b.2) In third parties 44,058.33 765.00 c) Allocation of subsidies of a financial nature 6,049.06 7,974.48 15. Financial expenses -12,673.09 -24,147.75 a) For debts with third parties -12,673.09 -24,147.75 17. Exchange rate differences -5,935.18 -2,777.56 II) FINANCIAL RESULT 47,770.76 -18,185.83 III) PRE-TAX EARNINGS 49,025.20 -93,371.44 16. Taxes on profits. 0 0 IV) RESULT FOR THE FINANCIAL YEAR 49,025.20 -93,371.44

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 285 Facts and Figures · Management

Assets

2019 2018 A) NON-CURRENT ASSETS 3,466,880.75 3,254,949.18 I. Tangible fixed assets 9,409.29 43,846.81 1. Computer applications 9,409.29 43,846.81 II. Property, plant and equipment 2,894,352.20 2,632,553.72 3. Technical installations 0.00 0.00 4. Machinery 2,351,722.91 2,214,113.67 6. Furniture 46,102.98 53,143.10 7. Equipment for information processing 490,276.99 359,047.63 9. Other fixed assets 6,249.32 6,249.32 V. Long-term financial investments 563,119.26 578,548.65 1. Equity instruments 521,373.35 531,373.35 5. Other financial assets 41,745.91 47,175.30 B) CURRENT ASSETS 21,421,361.14 18,378,662.65 I. Stocks 0.00 18,961.72 2. Raw materials and other procurements 0.00 18,961.72 II. Users, sponsors and debtors of activities and 5,513,843.51 6,564,360.69 other receivables 4. Debtors various 4,931,002.35 4,988,577.12 5. Personnel 2,724.78 2,724.78 7. Other credits with Public Administrations 580,116.38 1,573,058.79 III. Short-term financial investments 50,822.90 59,927.90 5. Other financial assets 50,822.90 59,927.90 V. Cash and other equivalent liquid assets 15,856,694.73 11,735,412.34 1. Cash and banks 15,856,694.73 11,735,412.34 TOTAL ASSETS (A+B) 24,888,241.89 21,633,611.83

286 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Human Resources

As at 31 December 2019, the IMIM Foundation is managing 719 people, of whom 305 have a direct employment contract with the Foundation. The rest correspond to personnel from other institutions that form part of the Hospital del Mar Medical Research Institute (IMIM) and that, through the agreement signed between all the institutions of the Institute on 17 June 2009 and subsequently ratified on 15 July 2014, are managed by the IMIM Foundation. The following table presents the composition of the IMIM, accredited as a Healthcare Research Institute by the Carlos III Health Institute (ISCIII) in the year 2014.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 287 Facts and Figures · Management

Distribution of Instituto IMIM personnel according to the programme to which they belong and the function they perform (31/12/2019)

Support/ Resear- PhD Tech- Programme Research Total chers Students nicians assistants Cancer 82 15 58 3 158 Epidemiology and Health 63 12 25 15 115 Services Biomedical Informatics 13 2 9 3 27 Neurosciences 84 11 53 4 152 Inflammatory and 112 19 50 4 185 Cardiovascular Disorders Miscellaneous 18 0 4 1 23 Management 0 0 1 42 43 Scientific and Technical 0 0 9 7 16 Services Total 372 59 209 79 719 % 51.74 8.21 29.07 10.99 100.00

288 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Distribution of Instituto IMIM personnel according to the programme to which they belong and gender (31/12/2019)

200 190 182

152 150

Women (450) 100

Men (269) 57 64 44 50

15 15

0 Researchers PhD Students Technicians Support / (372) (59) (209) Research assistants (79)

The 719 people correspond, in addition to the 305 employed by the IMIM Foundation, to the professionals employed by the PSMAR and to the contribution from the UPF to the Institute with 4 groups (Dr R. Maldonado, Dr M. Pastor, Dr L. A. Pérez-Jurado and Dr O. Valverde), as well as the contribution of two groups from the UAB (I. Anguelovski and O. Vilarroya) and from the Barcelona Beta Research Center (J. L. Molinuevo).

Retirements

Over the course of the year 2019, several people have left the management area due to retirement. In preparation for these retirements, a call was made for applications for a merit-based recruitment process to fill the following positions: Human Resources Director, Head of General Services, and Head of Quality Service (the latter has been temporarily filled by internal promotion). In parallel, in the month of July 2019, Dr Joaquim Bellmunt formally communicated his resignation from his post as IMIM Director. Temporarily, and following approval by the IMIM Foundation Board of Trustees on 4 October 2019, Jordi Martínez, the PSMAR’s Director of Innovation and Digital Transformation, temporarily took over the Director’s management functions.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 289 Facts and Figures · Management

2nd Plan for Equal Opportunities for Women and Men 2018-2021

In the month of June 2019, the Management Committee and Board of Trustees of the IMIM Foundation approved its 2nd Plan for Equal Opportunities for Women and Men 2018-2021. This Plan, drawn up and agreed by an Equality Committee made up of equal numbers of workers’ and Institution representatives, was born with a twofold objective: firstly, to continue providing a response to the institutional commitment of advancing towards an Institution free of any form of discrimination between men and women as expressed in the year 2013, with the drafting of what became the 1st Plan for Institutional Equality and, secondly, to continue complying with the Catalan, Spanish and international legislative framework which involves the commitment of ensuring that the right to equality and to non-discrimination of men and women is made effective in all spheres of personal and professional life.

The IMIM signs the charter committing to gender equality in Catalan medical research

This year, the IMIM has signed the charter committing to equality in Catalan medical research, within the framework of the first Health Sciences Gender Summit, organised by the Agency for Health Quality and Assessment of Catalonia (AQuAS) and the Health Department of the Catalan Government in collaboration with the “la Caixa” Foundation. The Commitment Charter, signed by the directors and representatives of the Catalan health research centres and institutes, includes twelve commitments to put an end to gender inequality in the research system in Catalonia, with measures relating to equal salaries for the same responsibility and professional level, eliminating obstacles that prevent women from advancing in their scientific career, and promoting changes in the organisational culture to eliminate systemic barriers or stereotypes. A work plan has also been defined that will be developed over a year in order to accelerate women’s progress and leadership in this area.

290 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Compulsory working hours register (Royal Decree-Law 8/2019, of 8 March)

March 2019 saw the publication of Royal Decree-Law 8/2019, of 8 March, on urgent measures for social protection and against precarity in working hours, which, among others, establishes measures on the obligation of having a register of working hours for all men and women workers. This measure, of obligatory compliance, has represented the development and improvement of the system of the pre-existing attendance check that already exists, in order to adapt it to the requirements established in the aforementioned Royal Decree-Law. The new system entered into force at the Institution on 13 May 2019 and its implementation was carried out in various trial phases in order to guarantee that the definitive system responds to the regulations in force.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 291 Facts and Figures · Management

Quality

Accreditations and certifications

Current status of IMIM Foundation accreditations and certifications

Accredited Require- Date Date of last Next or Certified Organisation ments obtained renewal renewal Services ISCIII Ac- Carlos III IIS-IMIM creditation Health Insti- 17/02/2014 17/02/2019 2024 Guide tute (ISCIII) CERCA CERCA Hospital del Centres (Research Mar Medical evaluation Centre of 05/03/2013 23/11/2016 2021 Research Ins- question- Catalonia) titute naire Institution European Charter for Resear- EURAXESS Centre for chers and Excellence the Code European in Human 25/06/2015 20/03/2018 2021 of Conduct Commission Resources in for the Re- Research cruitment of Resear- chers

292 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Accredited Require- Date Date of last Next or Certified Organisation ments obtained renewal renewal Services BAPP Group ISO 9001 Acció (Gen- TECNIO + own re- 07/03/2016 - 2020 Cat) Centre quirements WADA Anti-doping Code and Laboratory of internatio- WADA 15/11/1985 01/01/2017 2020 Catalonia nal standards Anti-doping ISO 17025 Laboratory of ENAC 24/11/2000 29/10/2019 2021 standard Catalonia Scientific and Technical ISO 9001 AENOR 23/07/2017 23/07/2017 2020 services and standard Biobank Criteria of the Scienti- fic Founda- FCAECC tion of the accredited AECC 22/05/2018 Spanish centre Association Against Cancer Catalan Ministry of Clinical Re- Best Clini- Health Inspection search Unit cal Practice 06/09/2017 February 2021 (Phase I) standards 2019 Government of Catalonia Innovation UNE Management 166002 AENOR 15/09/2017 - 2020 System Standard

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 293 Facts and Figures · Management

Accumulated IMIM accreditations and certifications

Renewal of accreditation as an IIS (Healthcare Research Institute)

The first renewal of accreditation as a Healthcare Research Institute was obtained on 17 February 2019, after 5 years of initial accreditation as an Institute in February 2014. Also, this year the new guide was published for the accreditation of institutes with the date of 12 April 2019, and work has commenced internally to start up actions to respond to this in the next accreditation.

294 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

IMIM Strategic Plan

The current IMIM Strategic Plan is defined in the period of development of 2016-2020. Annually there is a review of the accomplishment of the actions defined, with the last follow-up conducted in December 2019.

Lines of the IMIM Strategic Plan 2016-2020

1. Research strategies 1.1. Focus research on areas of excellence 1.2. Ensure generational takeover consistent with the research strategy 1.3. Strengthen innovation and transfer 1.4. Define and roll out a Strategic Partnerships Plan 2. Sustainability strategies 2.1. Ensure research sustainability 3. Organisation strategies 3.1. Ensure efficiency in research management 3.2. Reformulate the research management model 3.3. Reformulate the management model of professionals

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 295 Facts and Figures · Management

Communication

During the year 2019, a total of 2,310 news items referring to the IMIM were registered in the media. The number of impacts was higher by 20% with respect to the same period of the year 2018, thanks to the increase in the number of press releases made and the good results obtained with the issues that have been worked with as press releases. Highlights include the extraordinary results obtained with the press release “80% of the adult population in Spain will present obesity or overweight by the year 2030” with 411 appearances, as well as good results obtained by the press release “Effectiveness of new treatment for bladder cancer is demonstrated” with 173 appearances, and “Age when starting smoking is related with the increase in smoker mortality” with 101 appearances. Of the overall press appearances detected, 92.5% were the result of the press releases produced by the Communication service and only 7.5% were due to demands not directly linked to any information issued by the Institution, a percentage that denotes its proactivity with regard to the media. In this period there were 45 press releases made, thirteen more than during the same period of 2018.

Advertising value of news appearances 2019

1% 79% 4% 15%

Web TV Press Radio

296 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Impacts per programmes

54 Neurosciences 362 357

464 Cancer

1,012 Epidemiology and Public Health

Web notes

Web notes are those issues chosen that have scientific and/or institutional transcendence but that would not have repercussion as a press note sent to the media, thus offering a new communication resource. This year there have been 30 web notes produced, 7 notes more than during the same period in the year 2018.

Website

During the year 2019 there were a total of 112,191 visits (up by 9%) to the website with visitors viewing 428,467 pages (up by 7%) and some 29% of them being new users. If we study the origin of the visits by countries, we find that some 64% of the visits come from Spain, followed by the United States (7.8%), Chile (6%), Argentina (3%) and Mexico (2%). It has also been confirmed that the most visited pages are the main page and the job offers page, followed by the news on the effects of Ecstasy (news article 2017) and the research programmes space. The website is consulted some 65.8% of the time via PC, 31.5% of the time via mobile telephone and 2.7% via tablet.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 297 Facts and Figures · Management

Distribution by time, by countries and by devices of visits to the website in 2019

Where are your users? Sessions by country

Spain: 39,842 United States: 4,860 Chile: 3,715 Argentina: 1,828 Mexico: 1,351

What are your main devices? Sessions by device computers

Tablets 2.7%

Mobiles 31.5%

65.8% Computers

298 IMIM 2019 Hospital del Mar Medical Research Institute > SUMMARY Facts and Figures · Management

Intranet

A total of 781 news items were published, of which 474 are scientific sessions for the agenda space, a space that was created in February 2017 and which incorporates the agenda of all the sessions carried out at the PRBB. The rest of the most numerous news item types are Institutional Information (110), the weekly publication on research grants, Inforecerca (84) and Press Releases (45).

Social Media Networks

Twitter

The IMIM Twitter account (@imimat) current has 4,685 tweets published and 7,456 followers, some 1,700 more than at the end of 2018. We were pioneers, in the year 2008, in using, on a scientific level, what is today a consolidated tool that attracts new followers day after day. The most outstanding tweets of the period were “Dr Fitó and her team have explained to visitors from @LaMarato their research into the functions of good cholesterol” (with 4,336 reactions) and “A team led by @OncoBellmunt demonstrates the effectiveness of a new treatment for bladder cancer” (with 4,131 impressions), “This morning we are presenting the project #PENSAciència” (3731 views) and “We are now at the Science Fair” (3487 views)

Flickr

The Flickr has been established as a repository of images and currently hosts 1,898 images, organised into 57 albums. During the year 2019 the photographic gallery has been increased by some 550 images.

> SUMMARY IMIM 2019 Hospital del Mar Medical Research Institute 299 Facts and Figures · Management

Scientific communication acts and events for the general public

For the general public

Open Day

This is the Open Day that is organised annually at the PRBB with the participation of professionals from all the centres forming part of it. This tenth edition, which was held on 5 October, enjoyed the collaboration of some 260 volunteers and around 2,000 people were able to enjoy the activities and workshops, the guided tours of the laboratories, the scientific talks, and the activities for children. Participating from the IMIM were 86 volunteers, 7 laboratories and/or installations, plus the activity “Measure your cardiovascular health” in which 350 people participated and the talk “The evil superpowers of metastatic cells” which was given by laboratory researchers led by Toni Celià-Terrassa.

“Live research with the Marató”

A project by the Marató de TV3 Foundation to raise awareness of some of the projects sponsored by the Marató at research centres. Two guided tours are organised led by the researchers of a project funded by the Marató, on this occasion on a research project about the functions of good cholesterol, led by Dr Fitó.

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Exhibition at Ciutadella/Vila Olímpica Metro

The exhibition “Leonardo da Vinci at the PRBB”, organised by all the PRBB centres, was housed in the walkway of the Ciutadella/Vila Olímpica station on L4 of the Barcelona Metro, from the end of July to mid-November. The aim was to offer a view of human biology at the same time as commemorating the 500th anniversary of the death of Leonardo da Vinci (1452-1519). The guiding thread of the exhibition “from macro to micro”, follows the profile of the research that is conducted at the PRBB, where over 800 scientists study diverse aspects of biomedicine from all spheres and levels; from the smallest (molecules and DNA) to the largest (peoples and interaction with the planet), passing through cells and tissues.

Science Festival 2019

On 26 and 27 October, the 13th edition of the Science Festival was organised with the aim of promoting scientific knowledge among citizens. The Science Festival is an activity coordinated by the Barcelona Science programme, an initiative from Barcelona City Council, which this year has received 15,000 visitors and in which 150 organisations have participated (research centres, universities, companies, associations and science communication professionals) with the aim of bring scientific and technological knowledge closer to society. The IMIM participated with 3 micro-talks and a space for Debate.

For university students

A group of 33 third-degree Pharmacology students from Blanquerna have visited various facilities at our centre related with their studies: the Pharmacy Service at Hospital del Mar, the IMIM’s Clinical Research Unit, the Integrated Pharmacology and Systems Neuroscience Laboratory and the Biobank. A group of 40 students from Medical Laboratory Technology at the University of Ghent, Belgium, came to visit our centre and were able to visit the cancer molecular therapy laboratory and the Biobank.

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For secondary and A-level students

Bringing Science Closer to Secondary Schools Project (ACCÉS)

Following with the ACCÉS project, up until the month of October we were visited by 8 centres from around the Catalan territory, which meant participation in the programme of over 180 students. The ACCÉS project is included in the Escolab Project, an initiative from the Barcelona Science Programme of the Institute of Culture and from the Scientific Culture Programme of the Institute of Education of Barcelona City Council, which groups together the activities of the research centres, which provides us with greater visibility.

Biojunior

This is an activity addressing young people in the last year of compulsory education and the first year of A’ Levels, organised by the PRBB and open to some 300 students. In this fourth edition the IMIM has participated with two stations: the laboratory of the research group in Integrated Pharmacology and Systems Neuroscience and the research group in Doping in Sport. Furthermore, an IMIM researcher took part as a speaker in the round table on scientific careers.

Science talks for students (4th year senior-school students)

Scientific lectures offered by the PRBB at secondary centres in collaboration with Scientific Culture of the Municipal Education Institute of Barcelona. On this occasion, Dr Francesc Colom gave a talk on “Mental Illnesses: Bipolar Disorder”.

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For children’s audiences

Interview a scientist

This is an activity organised by the PRBB aimed at children in the second cycle of primary school (9-12 years), which commenced in the year 2014. It is programmed within the educational activities that are offered at primary centres and there are some 4/5 per school year. The IMIM takes part with 1 researcher every season.

Internal events

IMIM Retreat

This year saw the organisation of the 3rd IMIM Retreat on 29 May, a day of science with the participation of all the IMIM researchers and where each research programme presents 5 relevant projects from its area. The Retreat’s aim is to raise the visibility of the most relevant projects being worked on in each Research Programme, with a space for questions and discussion, with the aim of generating new synergies and scientific exchange between the different groups and improving our institution’s scientific competitiveness.

IMIM Management Area Retreat

July 2019 saw the First IMIM Management Area Retreat. This was a day where the usual working environment and the responsibilities of the Management Area were changed, for a day of activities where employees could relate to each other in a different way, find synergies and complicities and where concepts have been worked on such as teamwork, cohesion, communication and the importance of individual attitude in the achievement of common objectives. The continuity of this initiative is already envisaged, with the organisation of a new retreat day for 2020 with new challenges and goals.

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Other events

Events for professionals

During this period we have received a visit from Friends of the Hospital del Mar with the aim of finding out about the research lines being developed at the IMIM, as well as the visit of senior management from the Carreras Foundation and a visit from Dr Toshiyasu Ichioka, representative of Riken Europe who was invited by CERCA. Furthermore, we have collaborated with the organisation of III Optimizing Immunology, a scientific meeting that brings together oncologists, pathologists and basic researchers to find out about the latest developments in treatments with immunotherapy and we have collaborated in the organisation of two “Clinical Observation Programs”.

International Day of Women and Girls in Science

To commemorate this International Day this year the IMIM joined the campaign on the social media networks, #SheInspiredMe, which was being followed by some of the PRBB’s centres. The campaign highlighted the role of a woman of science (famous or not) that has inspired us. To carry it out, some men and women researchers were asked to propose a researcher that has inspired them and to explain to us why.

Furthermore, a talk was organised at the Institut La Salle Barceloneta secondary school and given by Dr Judith Marín, an intensive care physician at the Hospital del Mar and member of the Research Group in Critical Pathology, in which she explained to 60 A’ Level students her experience in a scientific career.

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Governing Bodies

The Board of Trustees is the top governing body of the Foundation and is comprised of representatives from the Catalan Ministry of Health, Parc de Salut Mar, the Catalan Ministry of Economy and Knowledge and the Pompeu Fabra University (UPF) and Autonomous University of Barcelona (UAB).

Board of Trustees

Chair Minister of Health. Government of Catalonia Alba Vergés i Bosch

First Vice-president Minister of Economy and Knowledge. Government of Catalonia Maria Àngels Chacón i Feixas

Second Vice-president Vice-president of the Governing Council. Consorci Parc de Salut Mar de Barcelona Davide Malmusi

Third Vice-president Rector of the Autonomous University of Barcelona Margarita Arboix Arzo

Fourth Vice-president Rector of the Pompeu Fabra University Jaume Casals Pons

Ex-officio member General Director for Research Ministry of Economy and Knowledge. Government of Catalonia Joan Gómez Pallarès

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Members

Appointed by the Ministry of Health. Government of Catalonia: Robert Fabregat Fuentes, Montserrrat Llavayol Giralt, Anna Meseguer Navarro

Appointed by the Ministry of Economy and Knowledge. Government of Catalonia: Iolanda Font de Rubinat García, Lluís Rovira Pato, Francesc Xavier Grau

Appointed by Barcelona Mar Health Park Consortium: Olga Pané Mena, Julio Pascual Santos, Josep Aumatell Canellas, Narcís Pérez de Puig (Secretary)

Appointed by the Autonomous University of Barcelona: Armand Sánchez Bonastre

Appointed by the Pompeu Fabra University: José García Montalvo

Appointed by the Centre for Genomic Regulation Foundation: Appointment pending

Appointed by the Barcelona Institute for Global Health (ISGlobal) Foundation: Appointment pending

Appointed by the Barcelona Biomedical Research Park Consortium: Jordi Camí Morell

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Executive Committee

Chair Catalan Health Institute (ICS). Ministry of Health. Government of Catalonia: Robert Fabregat Fuentes

Members

General Research Director Ministry of Economy and Knowledge: Joan Gómez Pallarès

Appointed by the Ministry of Economy and Knowledge: Lluís Rovira Pato

Appointed by the Autonomous University of Barcelona: Armand Sánchez Bonastre

Appointed by the Pompeu Fabra University: José García Montalvo

Appointed by the Barcelona Mar Health Park Consortium: Olga Pané Mena Narcís Pérez de Puig (Secretary)

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