Articles publicats (IRBLleida)
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L'IRBLleida és un centre de recerca conjunt entre la Universitat i el Departament de Salut de la Generalitat de Catalunya. Té com a funció potenciar les sinergies de recerca biomèdica entre ambdós institucions i està compromès en avançar en la recerca biomèdica com a mitja per millorar la salut de la població i facilitar una activitat assistencial òptima en situacions de malaltia. [Més informació].
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- ItemOpen AccessBrain and circulating EV proteome signatures in schizophrenia as prognostic markers for age-related dementia(Springer Nature, 2026-02) Sánchez Milán, Jose Antonio; Mulet, Maria; Molet, Itziar; Lisa Molina, Julia; Font Alberich, Maria; Lorca, Cristina; Gea Sánchez, Montserrat; Bellon, Filip; Batalla, Iolanda; Meana, Javier; Callado, Luis; Morentin, Benito; Ramos Miguel, Alfredo; Kalaria, Raj; Serra Maqueda, Aida; Gallart Palau, Xavier RamonSchizophrenia (SZ) is epidemiologically linked to an increased risk of developing age-related dementias (ARD) predominantly characterized by Alzheimer's disease and vascular dementia. However, the molecular mechanisms underlying this association remain insufficiently elucidated. Extracellular vesicles (EVs) play a critical role in neuropathological processes and offer a promising avenue for identifying shared disease mechanisms and potential circulating markers for patient stratification. Here we used a two-phase systems biology approach integrating discovery-driven proteomics with a targeted validation strategy using data-independent acquisition mass spectrometry (DIA-MS) in a large, independent SZ cohort. First, we analyzed brain-derived EVs (bEVs) from post-mortem SZ and ARD subjects to identify shared molecular signatures. Next, we validated the presence and circulation of these bEV markers in circulating plasma EVs (pEVs) using DIA-MS data. Remarkably, SZ and ARD bEV proteome and peptidome showed overlapping alterations in neuronal connectivity, synaptic integrity, neuroinflammation, and metabolism. Unsupervised clustering analysis of correlated bEV/pEV markers stratified SZ patients into two clusters: high dementia risk and control-like profiles. Collectively, these data emphasize the significance of bEVs as crucial mediators of shared neuropathogenic mechanisms in SZ, and ARD. Furthermore, we identified a set of pEVs markers, including proteins and specific peptides, with a robust and promising bench-to-bedside trajectory that may facilitate the stratification of SZ patients at risk for ARD.
- ItemOpen AccessEnvironmental Drivers of Respiratory Emergency Admissions: The Role of Tropospheric Ozone and Humidity in Lleida, Spain (2010-2019)(Springer Nature, 2026-01) Llobet, Cecilia; Martínez Alonso, Montserrat; Justribó, Elena; Ortet, Jaume; Yuguero Torres, OriolBackground: Tropospheric ozone (O₃) is a secondary air pollutant associated with respiratory morbidity. Lleida is an inland Mediterranean city with a continentalized climate, frequent winter thermal inversions and hot, dry summers, where ozone episodes and high humidity often co-occur under stagnant atmospheric conditions. This study explores the association between air pollutants, weather variables, and respiratory emergency admissions in Lleida, Spain. Methods: We conducted a time-series analysis using distributed lag non-linear models (DLNM) on hospital emergency room admissions for acute respiratory conditions in Lleida (2010–2019). Data on weather (temperature, humidity, solar radiation) and air pollution (O₃, NO₂, PM10, SO₂) were obtained from local monitoring stations. The primary outcome was the daily number of admissions for respiratory conditions (ICD-10 codes J09–J18, J20–J22, J44.1, J45.9). Results: A total of 19,428 respiratory admissions were recorded. High O₃ concentrations and elevated relative humidity were significantly associated with increased admissions, even after adjusting for temperature and solar radiation. The strongest effects were observed with delayed lags (up to 21 days). NO₂, PM10, CO and SO₂ levels did not show a significant association. Conclusions: Our findings support a significant and independent association between elevated ozone concentrations, high humidity, and respiratory emergencies. These results highlight the need for public health strategies and policy interventions focused on environmental risk forecasting and air quality management, particularly in vulnerable inland Mediterranean regions.
- ItemOpen AccessTracing the molecular route to progression in miRNA-biogenesis-defective thyroid lesions(American Society for Clinical Investigation, 2026-02) Chong, Anne Sophie; Roca, Carla; Morales Sánchez, Paula; Dorca, Eduard; Barea, Verónica; Ruz Caracuel, Ignacio; Valderrabano, Pablo; Rovira, Carlota; Jou, Cristina; Bouron Dal Soglio, Dorothée; Chernock, Rebecca; Torrezan, Giovana; Pusztaszeri, Marc; Cameselle Teijeiro, José; Matias-Guiu, Xavier; Alvarez, Clara; Salvador, Héctor; Wasserman, Jonathan; Leandro García, Luis Javier; Foulkes, William; Andrés León, Eduardo; Casano Sancho, Paula; Rivera, BarbaraGermline and somatic changes in DICER1 and DGCR8 microprocessors confer risk of developing benign and malignant thyroid lesions, yet the molecular events driving malignant transformation remain unclear. We trace the molecular trajectories from benignity to malignancy in DICER1- and DGCR8-mutated thyroid lesions using multiomic profiling on over 30 DICER1-/DGCR8-mutated samples. Our findings reveal a progressive, specific, and linear accumulation of genetic changes, which when combined with enhanced downregulation of miRNAs distinguished DICER1-/DGCR8-malignant lesions from their benign counterparts. Compensatory hypomethylation of miRNA-encoding genes characterized DICER1-/DGCR8-benign lesions, but as the tumors progressed to malignancy, methylation was partly reimposed, reversing the attempts to activate miRNA-encoded genes and further compromising miRNA production. Transcriptomic analyses revealed mutation-specific effects on the microenvironment, whereby DICER1 mutations activated canonical thyroid cancer progression pathways, whereas altered DGCR8 associated with immune-related changes. This work unveils specific molecular events underlying malignant progression of miRNA-biogenesis-related thyroid tumors and identifies potential biomarkers and disease etiology mechanisms.
- ItemOpen AccessMultilayer metabolomic integration reveals bioenergetic disruption in Long COVID(Springer Nature, 2026-01) García Hidalgo, María; Mota Martorell, Natàlia; González, Jessica; Benítez, Iván; Company Marín, Idoia; Jové Font, Mariona; Barbé Illa, Ferran; Amigó, Núria; Pamplona Gras, Reinald; de Gonzalo Calvo, David; Torres Cortada, GerardBackground Long COVID represents a significant health challenge, with 10–20% of patients with COVID-19 experiencing persistent multiorgan symptoms. The heterogeneity of clinical manifestations, combined with an incomplete understanding of the underlying molecular mechanisms, limits the improvement of patient management. Circulating metabolomic profiling constitutes a promising tool to address these limitations. In this context, we aim to investigate long-term metabolic disruptions in Long COVID through multilayer integration of plasma metabolites. Methods The study population included 42 survivors of critical COVID-19 who attended a comprehensive clinical evaluation conducted 12 months postdischarge. Plasma biochemicals, including lipoproteins, lipids, glycoproteins and metabolites were quantified using proton nuclear magnetic resonance spectroscopy (H-NMR). Circulating tricarboxylic acid (TCA) cycle intermediates and protein damage markers were detected by gas chromatography‒mass spectrometry (GC/MS). A machine learning-based feature selection approach was employed to identify the multilayered metabolic signature. Generalized additive models (GAMs) were used to explore associations between individual metabolites and specific dimensions of Long COVID. Results Univariate analysis revealed significantly elevated levels of alpha-ketoglutarate (aKG) and reduced levels of creatine in patients with Long COVID. A nine-metabolite and damage marker signature [aKG, carboxymethyl-cysteine (CMC), carboxymethyl-lysine (CML), creatine, fumarate, lactate, low density lipoprotein particle size (LDL-Z), 2-succinyl-cysteine (2SC) and tyrosine] was identified through the integration of Random Forest with Boruta and Sparse Partial Least Squares regression. This signature effectively classified patients with Long COVID (a cross-validated AUC of 0.91). In the GAM models, aKG, CMC, CML and creatine were associated with distinct Long COVID dimensions, including cognitive, functional and respiratory impairments. Conclusions Multilayer metabolomic integration reveals persistent bioenergetic disruption in patients with Long COVID. The identified metabolic profile offers promising biomarkers for medical decision-making. Modulating key metabolites could potentially mitigate specific symptoms of long COVID.
- ItemOpen AccessBarriers and facilitators from the patients' perspective in the follow-up of carpal tunnel syndrome and subacromial impingement syndrome: A qualitative study(Board, 2026-02) Artigues-Barberà, Eva; García-Martínez, Ester; Palacín Peruga, José María; Ortega Bravo, MartaIntroduction Chronic musculoskeletal pain is one of the leading causes of disability worldwide, affecting 11–50% of the population. In Spain, it accounts for up to 50% of the chronic pain consultations conducted in primary care settings. The most common disorders are carpal tunnel and subacromial impingement syndromes, with treatments, including surgical and nonsurgical approaches, notably the use of ultrasound-guided injections to improve symptoms. Methods A qualitative, phenomenological, and inductive study was conducted on patients diagnosed with carpal tunnel syndrome or subacromial impingement syndrome at primary care centers in Lleida to identify patient‑reported domains relevant to the routine follow-up of CTS and SAIS in primary healthcare, and to examine barriers and facilitators of treatments to inform patient‑centered follow-up protocols. Purposive sampling was used, and five focus groups were organised, selecting participants aged >18 years with or without prior surgical treatment. Data were collected between December 2022 and February 2023 using a semi-structured guide. The focus groups were recorded and thematically analysed using Atlas.ti. Results Twenty-one patients aged between 44–75 years, predominantly women, participated in the study. The results were organised into six themes and 12 subthemes. The barriers identified were delays in diagnostic testing, overload of healthcare personnel, lack of coordination between care levels, and brevity of consultations. Effective communication, empathy of primary care professionals, and prompt management of treatments, such as injections, were highlighted as facilitators. Conclusion This study highlighted the complexity of managing chronic musculoskeletal pain and the need for a multidimensional approach. The identified barriers, along with facilitators, such as effective communication and empathy of professionals, emphasize the relevance of strengthening problem-solving capacity in primary care and fostering better coordination between care levels. These findings suggest that addressing these aspects may support more tailored follow-up and contribute to improving patients’ experiences of care.