e-Repositori UPF :: Articles (Hospital del Mar Research Institute)

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Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC)
(Wiley, 2024) Chicharro, Pablo; Giménez Arnau, Anna Maria; Sánchez-Pérez, Javier
Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. Objectives: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. Methods: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. Results: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. Conclusions: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.
Serum vitamin B12 concentration is associated with improved memory in older individuals with higher adherence to the Mediterranean diet
(Elsevier, 2023) Domínguez-López, Inés; Casas, Rosa; Chiva-Blanch, Gemma; Martínez-González, Miguel Ángel, 1957-; Fitó Colomer, Montserrat; Ros, Emilio; Lamuela Raventós, Rosa Ma.; Estruch, Ramón
Background & aims: Vitamin B12 plays a crucial role in cognition, but its effect might be regulated by the presence of other micronutrients, such as folate. The aim was to evaluate the effects of vitamin B12 on cognitive performance according to adherence to the Mediterranean diet, and whether the Mediterranean diet also results in increased folate or vitamin B12 levels. Methods: This is a cohort study nested in a randomized controlled clinical trial performed in Hospital Clinic in Barcelona, Spain. A total of 170 participants of the PREDIMED trial (Barcelona - Hospital Clinic site) aged 55-80 years at high cardiovascular risk were included. Adherence to the Mediterranean diet was assessed using a validated 14-item questionnaire, memory function was evaluated with a battery of neuropsychological tests and serum vitamin B12 and folate were determined using an automated electrochemiluminiscence immunoassay system. Results: In the multivariable adjusted linear regression model, serum vitamin B12 concentration presented a significant correlation with memory function (r2 = 0.57; P = 0.028) in participants with high adherence to the Mediterranean diet whereas the correlation was weak and inverse for those who presented a low adherence to the Mediterranean diet (r2 = 0.37, P = 0.731). Mediterranean diet adherence showed a positive association with serum folate, but not with serum vitamin B12. Conclusions: In an older Mediterranean population at high cardiovascular risk, changes in serum vitamin B12 correlate with better memory function only in the context of a high adherence to the Mediterranean pattern, suggesting that the effects of vitamin B12 goes further than a mere nutritional requirement. Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the 11 participating centres. The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639 (https://www.isrctn.com/ISRCTN35739639).
Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: the FRAILMar study
(Oxford University Press, 2025) Madrid-Gambin, Francisco; Pérez-Sáez, María José; Gómez-Gómez, Àlex; Haro, Noemí; Redondo Pachón, María Dolores; Dávalos Yerovi, Vanesa; Marco Navarro, Ester; Crespo Barrio, Marta; Pozo Mendoza, Óscar J., 1975-; Pascual Santos, Julio; FRAILMar Study Group
Background. Sarcopenia and frailty are often overlooked in assessing kidney transplant (KT) candidates with chronic kidney disease (CKD), potentially leading to poor post-transplant outcomes. This study aimed to identify metabolites associated with frailty and sarcopenia in KT candidates from the FRAILMar study. Methods. Between June 2016 and June 2020, we evaluated frailty and sarcopenia in 173 KT candidates using the Physical Frailty Phenotype and EGWSOP-2 criteria, respectively. Seventy-five metabolic markers from targeted pathways, previously linked to CKD, sarcopenia or frailty, were measured in serum samples. These markers were analyzed using adjusted and weighted generalized linear models. Metabolomic data were integrated with multi-modal data, such as comorbidities, using a factor-based integration algorithm to identify metabolic phenotypes. Results. Increased metabolites related to energy metabolism and essential amino acids were associated with frailty, mainly Krebs cycle intermediates. Sarcopenic KT candidates showed lower levels of aromatic amino acids, and lower protein/muscle metabolism, energy metabolism and neurotransmission compared with non-sarcopenic patients. Unsupervised multi-modal integration revealed a high-risk metabolic phenotype characterized by the presence of sarcopenia, diabetes mellitus and low body mass index, with alterations in branched-chain amino acids and high activity of lactate dehydrogenase enzyme. Conclusions. Frailty and sarcopenia are common among KT candidates, and their metabolic status reveals notable disruptions in energy and amino acid metabolism. These findings highlight the value of a detailed metabolic assessment to more accurately evaluate patient health status prior to transplantation.
Asymptomatic inflammatory bowel disease diagnosed during colorectal cancer population screening in Catalonia: characteristics and natural history
(Wolters Kluwer (LWW), 2025) Brunet-Mas, Eduard; Márquez Mosquera, Lucía; Calvet, Xavier
Introduction: Inflammatory bowel disease (IBD) is usually diagnosed when symptomatic. Prognosis and evolution of preclinical IBD is largely unknown. However, colorectal cancer screening programs (CRCSP) detect a subset of patients with IBD with no symptoms. The aim of this study was to describe the natural history of asymptomatic IBD diagnosed through CRCSP. Methods: An observational, longitudinal, and retrospective study was performed at 22 centers in Catalonia between January 2010 and December 2019 including patients with asymptomatic IBD detected in the CRCSP. Demographic data and IBD characteristics, evolution, and treatment were recorded. Descriptive statistics and Kaplan-Meier analysis were used for the analysis. Data were given separately for IBD, Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBDU). Results: One hundred eighty-eight patients were included: 103 UC (54.8%), 60 CD (31.9%), and 25 IBDU (13.3%). Sixty-six (35.1%) were women, and the average age was 59.9 ± 5.9 years. Sixty-four patients (34.0%) developed symptoms after a median follow-up of 35.6 months. Diarrhea was the most frequent symptom for CD and IBDU (25.4% and 11.5%, respectively) and blood in stools for UC (21.4%). The median time to first symptom was 11.6 months. Treatment was prescribed in 135 patients (72.2%); mesalazine was the most prescribed drug (123 patients; 65.4%). Thirteen patients (6.9%) required biological treatment. None underwent surgery. Discussion: Around one-third of asymptomatic patients with IBD developed symptoms after a medium follow-up of 3 years. Only 6.9% required biological treatment, and none required surgery. Overall, prognosis of asymptomatic IBD seems better.
Development of SOCS1 mimetics as novel approach to harmonize inflammation, oxidative stress, and fibrogenesis in metabolic dysfunction-associated steatotic liver disease
(Elsevier, 2025) Bernal, Susana; Prieto, Ignacio; Kavanagh, María; Herrero del Real, Isabel; Manna, Sara La; Lázaro, Iolanda; Quiceno, Hernán; López-Sanz, Laura; Picatoste, Belén; Valdecantos, Pilar; Mas Fontao, Sebastián; Sala Vila, Aleix; Valverde, Ángela María; Marasco, Daniela; Egido, Jesús (Egido de los Ríos); Gómez Guerrero, Carmen
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease, encompassing a spectrum from simple steatosis to steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. As part of metabolic syndrome, MASLD/MASH is characterized by inflammation, oxidative stress, and fibrosis, highlighting the need for targeted therapies. The dysregulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and its negative regulators the suppressors of cytokine signaling (SOCS), plays a critical role in liver function and contributes to MASLD progression. Aim: Based on a SOCS1 functional domain, we developed mimetic peptides (linear and cyclic) targeting JAK activity and assessed their hepatoprotective potential in experimental MASLD/MASH. Results: In dietary mouse models of MASLD/MASH, the administration of peptides ameliorated liver damage at both early and advanced stages, as evidenced by significant decreases in serum transaminases and hepatic content of lipids, inflammatory cells, and collagen. Treatment attenuated hepatic STAT1/3 activation and downregulated genes involved in inflammation, fibrosis, and lipid metabolism. Livers from treated mice exhibited lower levels of oxidative damage markers, reduced expression of NADPH oxidase 1 (NOX1), and upregulation of the antioxidant genes catalase and superoxide dismutase. In vitro, the peptides were safe for hepatocytes at different doses and effectively counteracted palmitate-induced cytotoxicity, superoxide anion production, and cytokine and NOX1 expression, while increasing anti-inflammatory and antioxidant genes. Conclusions: SOCS1 mimetic peptides exhibit hepatoprotective effects in experimental MASLD/MASH by modulating lipotoxicity, inflammation, redox balance and fibrogenesis. This proof-of-concept supports their potential as candidates for preclinical MASLD therapy development.
Does plate fixation improve the Latarjet procedure for anterior glenohumeral instability?
(Elsevier, 2025) Portes, Alba; Santana Pérez, Fernando; Torrens, Carlos
The Latarjet technique is a procedure used to treat anterior glenohumeral instability with glenoid bone loss. Various fixation systems for the coracoid have been described in the literature. This study aims to compare the results in quality of life and complications between patients treated with plate and screws (GP) for coracoid fixation and those treated with screws (GSP) only. Material and methods A retrospective study including patients with anterior glenohumeral instability and glenoid bone loss treated with Latarjet at the same centre between October 2009 and February 2021. A total of 85 shoulders were analysed, of which 64 completed at least one year of follow-up. Patients with previous surgical history in the same shoulder, bone loss <10%, ligamentous hyperlaxity (Beighton score >6), and previous infections were excluded. Complications were recorded, and the WOSI and Rowe tests were used to assess quality of life and return to sports activity. Results Of the 64 patients, 35 were treated with a plate (GP) and 29 with screws (GSP). The mean age was 30 ± 8.78 years. Both groups were statistically comparable. No significant differences were found in the WOSI test (P = .140), the Rowe test (P = .380) or in complications (P = .692). A higher percentage of the GP group returned to sports activity (77.1% GP vs. 51.7% GSP, P = .039). Conclusions No statistically differences were observed in quality of life, complications, or re-dislocations. However, the use of a plate showed a greater predisposition to return to sports activity (P = .039) in patients with anterior glenohumeral instability.
Índice ECoTES de desempeño del sistema de seguridad y salud en el trabajo, resultados de un estudio piloto en seis países iberoamericanos
(World Health Organization, 2025) Benavides, Fernando G. (Fernando García); Cornelio, Cecilia Inés, 1979-; Carmenate, Lino; Barraza, Douglas; Gimeno Ruiz de Porras, David; Vives Vergara, Alejandra, 1971-; Rojas, Marianela; Palomo Cobos, Luis; López-Ruiz, María; Amable, Marcelo; Merino-Salazar, Pamela; Silva-Peñaherrera, Michael, 1984-
Objective: To describe and evaluate the methodology of the ECoTES index, after its implementation in a pilot study in six Ibero-American countries. The ECoTES index (Spanish acronym for surveys of working conditions, employment and health) is designed to measure the performance of national occupational safety and health (OSH) systems. Methods: The ECoTES index was calculated for each country based on two components: i) a 15-question survey answered by 47 experts from Argentina, Chile, Costa Rica, Spain, Honduras, and Peru; and ii) eight statistical indicators (total labor participation rate, female labor participation rate, rate of informal employment, percentage of gross domestic product allocated to social protection excluding health, percentage of the population covered by occupational risk insurance, percentage of the population covered by at least one social benefit, rate of fatalities due to occupational injuries, and rate of deaths attributable to occupational risks). Simulations were conducted with different weights given to each component, and the correlation between statistical indicators and the scores provided by experts was assessed. Results: The survey was answered without difficulty. In addition to enabling construction of the index, the responses also served to improve its wording. There was a significant correlation between the scores for the different components of the index (r = 0.66) and the country rankings in the different simulations (Spearman's rank correlation coefficient: between 0.95 and 1). Conclusions: The ECoTES index proved to be methodologically robust. It is the first indicator in the world to assess the performance of national OSH systems. Its periodic application will allow comparisons over time and between countries, and will help to foster improvements in national systems.
Loss-of-function Gαs rare disease variants exert mutation-specific effects on GPCR signaling
(American Association for the Advancement of Science (AAAS), 2025) Redfern-Nichols, Theo; O'Brien, Shannon L.; Huang, Xianglin; Medel Lacruz, Brian; Calebiro, Davide; Selent, Jana; Graham, Ladds; Martí Solano, Maria
G protein-coupled receptors (GPCRs) are transmembrane detectors of extracellular signals that activate heterotrimeric G proteins to regulate intracellular responses. Because there are only 16 Gα proteins that can couple to GPCRs, variation in a single Gα can affect the function of numerous receptors. Here, we investigated two mutant forms of Gαs (L388R and E392K) that are associated with pseudohypoparathyroidism type Ic (PHPIc), a maternally inherited rare disease. Gαs is encoded by an imprinted gene, resulting in the mutant form of Gαs being the only version of the protein present in certain tissues, which leads to tissue-specific disease manifestations. By integrating data from three-dimensional structures, GPCR-G protein coupling specificity, transcriptomics, biophysics, and molecular dynamics with systems pharmacology modeling, we identified GPCRs whose signaling could be altered by Gαs mutations in the kidney, a tissue involved in the pathophysiology of PHPIc. Analysis of G protein activation by the parathyroid hormone receptor 1 (PTH1R) revealed that L388R impaired Gαs interaction with the receptor, whereas E392K reduced the receptor-induced activation of heterotrimeric Gs. This indicates that different signal transduction steps can be altered by specific Gαs mutants associated with the same disease. These findings highlight the importance of investigating mutation-specific perturbations in GPCR signaling to suggest patient-specific treatment strategies. Furthermore, our methods provide a blueprint for interrogating GPCR signaling diversity in different physiological and pathophysiological contexts.
Monitoring of the oncological process for lung cancer in Spain: an expert consensus report
(Springer, 2025) Castro, Javier de; Alonso-Fernández, Patricia; Castrodeza, José Javier; Gayete, Ángel; Hernando, Florentino; Martínez-Olmos, José; Massutí, Bartomeu; Paz-Ares, Luis; Sisó-Almirall, Antoni; Vicente Baz, David; Molins, Laureano
Introduction: Continuous monitoring of the oncological process is essential for identifying inefficiencies and areas of improvement, enabling better resource allocation in the care of lung cancer patients. Objective: The objective is to define key indicators and identify critical variables for monitoring lung cancer care, aiming to improve early detection, reduce delays in diagnosis and treatment, and enhance biomarker research, ensuring timely and effective treatments for all patients. Methods: A multidisciplinary expert group conducted a consensus process based on a review of national guidelines and initiatives related to lung cancer care. The experts defined relevant indicators and identified variables for monitoring overall care, addressing delays, and improving biomarker research. The feasibility of incorporating these indicators into existing information systems was also assessed. Results: The proposed indicators provide a structured approach for assessing lung cancer care and outcomes. Their inclusion in healthcare information systems would improve the monitoring and evaluation of care quality and patient outcomes. Additionally, these indicators would also promote interoperability and continuous patient care across different centers and regions, allowing informed decision-making in the improvement of healthcare processes by those responsible for healthcare management. Conclusions: The adoption of standardized indicators for lung cancer care monitoring can drive continuous improvement in healthcare processes. Implementing these indicators in information systems will enable better resource allocation, timely and effective treatment, and enhanced coordination among healthcare providers, ultimately improving patient outcomes.
Icosapento de etilo: del ensayo REDUCE-IT a la práctica clínica
(Elsevier, 2025) Pedro-Botet, Juan
In addition to low-density lipoproteins (LDL), those containing apolipoprotein (Apo) B and with a diameter less than 70 nm, including the smaller triglyceride-rich lipoproteins, remnant particles, and lipoprotein(a), may independently contribute to atherosclerosis because they also cross the endothelium and penetrate the arterial intima. Although mild/moderate hypertriglyceridemia is a recognized vascular risk factor, only two studies, the Japan EPA Lipid Intervention (JELIS) and the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), using pure eicosapentaenoic acid (EPA) or icosapent ethyl (IPE), the stable ethyl ester of EPA, respectively, rather than a combination of docosahexaenoic acid (DHA) and EPA, have demonstrated a reduction in the rate of cardiovascular events. For this reason, it was deemed appropriate to examine the implications and applicability of the REDUCE-IT study in real-life settings. This analysis suggests a transversal therapeutic approach, based on both LDL cholesterol and triglycerides, for patients at very high cardiovascular risk to achieve an effective prevention. Furthermore, among patients in secondary prevention, treatment with IPE should focus on those with the highest vascular risk (recent acute coronary syndrome, post-infarction, angioplasty, and coronary bypass grafting).
Systematic review of the needs and health-related quality of life domains relevant to people surviving cancer in Europe
(Springer, 2025) Amat-Fernández, Clara; Garin Boronat, Olatz, 1979-; Luer-Aguila, Ricardo; Pardo, Yolanda; Briseño-Diaz, Renata; Lizano-Barrantes, Catalina; Ferrer, Montserrat
Purpose: To systematically review qualitative studies on outcomes, needs, experiences, preferences, concerns and health-related quality of life (HRQoL) of people surviving cancer in Europe in the last decade. Methods: Protocol registered (https://www.crd.york.ac.uk/PROSPERO , ID575065). Inclusion criteria: studies with qualitative methods, constructs related to HRQoL, and adults surviving cancer in Europe. The search was conducted in PubMed and Scopus since 2013. Abstracts and full text were revised, data extracted and study risk of bias assessed independently by two researchers. The primary outcomes were the themes arising from each study. A thematic analysis stratified according to the study objective was undertaken by grouping themes into categories. Results: Of 18,256 articles identified, 43 fulfilled the inclusion criteria: 16 studies with a generic objective and 27 with specific objectives. Seven categories (57 themes) emerged from the studies with a generic focus: Clinical Management (n = 16), Symptoms and Physical Function (n = 5), Psychological Function (n = 21), Social Function (n = 18), HRQoL (n = 3), Life Disruption (n = 6), and Individual Factors (n = 1). The 12 studies focused on treatment and care experiences stand out among those with specific objectives, with most themes fitting into the same seven categories. Conclusions: Results clearly showed the predominance of the social and psychological function domains over physical domains among people surviving cancer, additionally identifying specific needs in clinical management, such as information and communication, and relationship with and support from professionals. Therefore, these aspects should be incorporated into the evaluation of patient-centred initiatives for people surviving cancer. Limitations: only two databases were searched, and most European countries were not represented.
Treatment of functionally nonsignificant vulnerable plaques in multivessel STEMI: design of the VULNERABLE trial
(Permanyer Publications, 2024) Gomez-Lara, Josep; Vaquerizo Montilla, Beatriz; Gutiérrez-Ibañes, Enrique
Introduction and objectives:: The optimal treatment of nonculprit angiographic intermediate lesions (diameter stenosis 40%-69%) in patients with ST-segment elevation myocardial infarction (STEMI) is still unknown. Lesions with fractional flow reserve (FFR) - 0.80 are indicative of ischemia and benefit from revascularization. However, lesions with FFR > 0.80 and optical coherence tomography (OCT) findings of vulnerability have been hypothesized to cause adverse events during follow-up. The study aims to compare the efficacy of a preventive treatment with stent implantation plus optimal medical therapy vs optimal medical therapy alone for nonculprit intermediate lesions with FFR > 0.80 and OCT findings of plaque vulnerability in STEMI patients at 4 years of follow-up. Methods: This parallel-group, multicenter, controlled, single-blind, and 1:1 randomized trial will enroll a total of 600 STEMI patients with - 1 intermediate nonculprit lesions with FFR > 0.80 and OCT findings of plaque vulnerability. The primary endpoint is target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. The study will include a parallel registry of patients with FFR > 0.80 but without OCT findings of vulnerability. Vulnerable plaques are defined as lipid-rich fibroathermas with plaque burden - 70% and a thin fibrous cap (- 80 mm). Results:: The VULNERABLE trial will reveal the role of preventive treatment with stent implantation for nonculprit and functionally nonsignificant vulnerable plaques in STEMI patients. conclusions:: This is the first randomized trial of OCT-guided treatment of vulnerables plaques. Registered at ClinicalTrials.gov (NCT05599061).
Negative SA-VA difference during ventricular overdrive pacing of supraventricular tachycardia for the diagnosis of atrial tachycardia
(Elsevier, 2025) Adeliño, Raquel; Bazán, Víctor; Sarrias, Axel; Jiménez-López, Jesús; Aranyó, Júlia; Bisbal, Felipe; Andrés-Cordón, Joan F.; Rodríguez-García, Julián; Jordán Marchite, Pablo; Gonzalez-Matos, Carlos E.; Villuendas, Roger; Rivas-Gándara, Nuria; Almendral, Jesús
Introduction and objectives: The stimulus-atrial minus ventriculo-atrial interval (SA-VA) difference during ventricular overdrive pacing of a supraventricular tachycardia is used to differentiate atrioventricular reciprocating tachycardia (AVRT) from atrioventricular nodal re-entrant tachycardia (AVNRT), but positive values have always been reported. In atrial tachycardia, the SA conduction is unrelated to the tachycardia mechanism, allowing for negative SA-VA values. We postulated that a negative SA-VA may serve as a criterion for atrial tachycardia in patients with supraventricular tachycardia and ventricular overdrive pacing from the right ventricular apex. Methods: Multicenter data from ventricular overdrive pacing during atrial tachycardia (from 6 centers) and during AVRT and AVNRT (from 2 centers) were retrospectively and consecutively collected. The correct diagnosis was established using conventional criteria. The SA-VA difference was calculated for each case. The optimal SA-VA cut-off point for the diagnosis of atrial tachycardia was determined. Results: Out of 240 tachycardias analyzed, ventricular overdrive pacing succeeded in accelerating the atria to the pacing rate without tachycardia termination in 106 cases: 38 (36%) AVNRT, 33 (31%) AVRT, and 35 (33%) atrial tachycardias (all exhibiting long VA intervals). All atrial tachycardias had a negative SA-VA value, while all AVNRT and AVRT cases had positive SA-VA values. A SA-VA value lower than 0ms was the best cutoff, with an area under the curve of 1 and 100% sensitivity and specificity for the diagnosis of atrial tachycardia. Conclusions: A negative SA-VA difference is a novel and accurate criterion for the diagnosis of atrial tachycardia with long VA intervals.
Cystic fibrosis alters the structure of the olfactory epithelium and the expression of olfactory receptors affecting odor perception
(American Association for the Advancement of Science (AAAS), 2025) Caballero, Ignacio; Mbouamboua, Yvon; Weise, Susanne; López-Gálvez, Raquel; Couralet, Marie; Fleurot, Isabelle; Pons, Nicolas; Barrera Conde, Andrea; Quílez-Playán, Nayima; Keller, Matthieu; Klymiuk, Nikolai; Robledo, Patricia, 1958-; Hummel, Thomas; Barbry, Pascal; Chamero, Pablo
A reduced sense of smell is a common condition in people with cystic fibrosis (CF) that negatively affects their quality of life. While often attributed to nasal mucosa inflammation, the underlying causes of the olfactory loss remain unknown. Here, we characterized gene expression in olfactory epithelium cells from patients with CF using single-nuclei RNA sequencing and found altered expression of olfactory receptors (ORs) and genes related to progenitor cell proliferation. We confirmed these findings in newborn, inflammation-free samples of a CF animal model and further identified ultrastructural alterations in the olfactory epithelium and bulbs of these animals. We established that CFTR, the anion channel whose dysfunction causes CF, is dispensable for odor-evoked signaling in sensory neurons, yet CF animals displayed defective odor-guided behaviors consistent with the morphological and molecular alterations. Our study highlights CF's major role in modulating epithelial structure and OR expression, shedding light on the mechanisms contributing to olfactory loss in CF.
Linking birth experience and perinatal depression symptoms to neuroanatomical changes in hippocampus and amygdala
(American Association for the Advancement of Science (AAAS), 2025) Ballesteros, Cristina; Paternina-Die, María; Martínez-García, Magdalena; López Montoya, Gonzalo; Noguero, Inés; Desco, Manuel; Vilarroya, Óscar; Martín de Blas, Daniel; Carmona, Susanna
Childbirth is a life-changing event in a mother's life. While the transition to motherhood has recently been recognized as one of the most neuroplastic periods in adulthood, no study has yet explored whether the hippocampus and amygdala change during the peripartum in relation to childbirth experience and perinatal depression symptoms. In this longitudinal neuroimaging study, we assessed 88 first-time gestational mothers in late pregnancy and early postpartum and 30 nulliparous control women. We used optimized high-resolution MRI scans to quantify volumetric changes in the hippocampus and amygdala, along with their substructures. We found that increases in depression symptoms during the peripartum were positively correlated with changes in the right amygdala. A more challenging birth experience was associated with bilateral increases in hippocampal volume. These findings show that studying the neuroanatomical changes during the transition to motherhood can inform not only about adaptive processes but also about potential vulnerabilities, highlighting the importance of tracking perinatal experiences to enhance women's health.
MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer
(Elsevier, 2025) Del Rey-Vergara, Raúl; Galindo-Campos, Miguel A.; Rocha, Pedro P.; Masfarré, Laura; Menéndez, Silvia; Quimis, Fabricio; Rossell, Adrià; Iñañez, Albert; Gimeno, Ramón; Taus García, Álvaro; Rovira, Ana; Arriola Aperribay, Edurne
The introduction of immunotherapy as a first-line treatment for advanced small cell lung cancer (SCLC) represents significant progress, yet there remains an opportunity to further improve patient outcomes. Hepatocyte growth factor (HGF) receptor (MET) pathway activation promotes epithelial-mesenchymal transition, driving chemoresistance and potentially impairing the efficacy of immunotherapy. In SCLC mouse models, adding MET inhibition to chemo-immunotherapy (anti-PD-L1) reduces tumor growth, extends survival, and reshapes the tumor microenvironment by decreasing suppressive myeloid cell infiltration and enhancing the immune response. Analysis of pretreatment human SCLC tumor samples reveals that myeloid-enriched immune infiltrates may contribute to chemo-immunotherapy resistance. Elevated serum HGF levels are associated with a mesenchymal and inflamed phenotype, suggesting that patients with these characteristics might benefit from MET inhibitor-based therapeutic strategies. These findings provide strong preclinical and translational evidence supporting MET inhibition as a therapeutic approach to overcome treatment resistance, enhancing the immune response and improving outcomes in biomarker-defined subsets of SCLC patients.
The Mediterranean diet displays an immunomodulatory effect that correlates with beneficial changes in carotid atherosclerosis
(Oxford University Press, 2025) Ruiz-León, Ana Maria; Camafort, Miguel; Sala Vila, Aleix; Gilabert, Rosa; Núñez, Isabel; Castro-Barquero, Sara; Fitó Colomer, Montserrat; Lamuela Raventós, Rosa Ma.; Pintó Sala, Xavier; García-Arellano, Ana; Ros, Emilio; Estruch, Ramón; Casas, Rosa
Influence of age on treatment and prognosis in ovarian cancer patients
(MDPI, 2025) Mancebo Moreno, Gemma; Solé-Sedeño, Josep Maria; Fabregó, Berta; Pinto, Giovanna; Vizoso-Expósito, Adrián; Álvarez, Marta; Sabaté-Garcia, Rosa Ana; Miralpeix, Ester
Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of this study is to assess age-specific differences in treatment and survival outcomes for ovarian cancer in women aged 70 years or older. Methods: This retrospective study included ovarian cancer patients treated at the Hospital del Mar, Barcelona, between 2016 and 2022. Patients were stratified into two groups: <70 and ≥70 years. Clinical and pathological data were analyzed, and hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS) were calculated using Cox proportional hazards regression models. Multivariate analysis was performed to compare outcomes. Results: A total of 110 patients were included (73 <70 years, 37 ≥70 years). Among the older group, 80.5% were diagnosed at advanced stages (III-IV), compared to 63% in the younger group (p = 0.012). Patients aged ≥70 were more likely to undergo interval surgery (p = 0.053) and receive non-standard treatment (p = 0.023). Complete cytoreduction was achieved in 95.8% of younger patients versus 81.3% of older patients (p = 0.024). Age ≥70 did not significantly impact DFS (p = 0.091), but OS was significantly worse in the older group (44.4% vs. 67.2%, p = 0.014). Conclusions: Older women (≥70 years) with ovarian cancer are more likely to be diagnosed at advanced stages, receive non-standard treatment, and achieve suboptimal cytoreduction compared to younger patients. While DFS was similar across age groups, older age was associated with worse OS, highlighting the need for age-tailored treatment strategies.
Regulation of WNT16 in bone may involve upstream enhancers within CPED1
(Nature Research, 2025) Martínez-Gil, Núria; Herrera-Úbeda, Carlos; Gritti, Nicola; Roca Ayats, Neus; Ugartondo, Nerea; García-Giralt, Natalia; Ovejero Crespo, Diana; Nogués Solán, Xavier; Garcia-Fernàndez, Jordi; Grinberg, Daniel; Balcells, Susana
WNT16 stands up as an essential gene for bone homeostasis. Here, we present new evidence of the functional role of a particular region within WNT16. Performing 4 C chromatin conformation analysis in three osteoblast-related cells (the human fetal osteoblast hFOB 1.19 cell line, Saos 2 osteosarcoma cell line and mesenchymal Stem Cells -MSC-), we identify physical interactions between the proximal part of WNT16 intron 2, shown here to be an active promoter in Saos 2 osteosarcoma cells, and several putative regulatory regions within CPED1. Analysis of previously published RNA-seq data from hFOB cells disclosed low expression of a region located downstream of this promoter. Our results suggest a novel regulatory mechanism of WNT16 in bone, mediated by physical interaction with various enhancer regions within CPED1.
Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation
(Elsevier, 2025) Khoury Damaa, Michella; Gil Gómez, Gabriel; Meunier, Alice
Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC). Here, we show that Ccno is activated at the crossroads of the onset of MCC differentiation, the entry into the MCC cell-cycle variant, and the activation of the centriole biogenesis program. Its absence blocks the G1/S-like transition of the cell-cycle variant, interrupts the centriologenesis transcription program, and compromises the production of centrioles and cilia in mouse brain and human respiratory MCCs. Altogether, our study identifies CCNO as a core regulator of entry into the MCC cell-cycle variant and the interruption of this variant as one etiology of RGMC.

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