Repositori Obert UdL

The institutional repository collects, manages, disseminates and preserves publications in open access derived from the academic and research activity of the University of Lleida.

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Open Access
Safety, tolerability, immunogenicity, and efficacy of ABvac40 active immunotherapy against Aβ40 in patients with mild cognitive impairment or very mild Alzheimer's disease: A randomized, double-blind, placebo-controlled phase 2 study
(Wiley, 2025-09) Pascual Lucas, María; Lacosta, Ana María; Montañés, María; Canudas, Jesús; Loscos, Jorge; Monleón, Inmaculada; Allué, José Antonio; Sarasa, Leticia; Fandos, Noelia; Romero, Judith; Sarasa, Manuel; Torres, Mireia; Whyms, Dermot; Terencio, Jose; Piñol Ripoll, Gerard; Boada, Mercè
Introduction: ABvac40 is an investigational active immunotherapy (vaccine) targeting Aβ40. This study assessed the safety and immunogenicity of ABvac40 in patients with amnestic mild cognitive impairment or very mild Alzheimer's disease. Methods: AB1601 was a multicenter, randomized, double-blind, placebo-controlled phase 2 study. Patients (n = 124) received five monthly injections plus a 10-month booster of ABvac40 or placebo, with 18-24 months of follow-up. Primary endpoints included safety, tolerability, and immunogenicity. Secondary endpoints assessed immune response, neuropsychological changes, and disease biomarkers. Results: Treatment-emergent adverse events (TEAEs) and serious TEAEs were comparable between ABvac40 (90.6% and 26.6%) and placebo (93.3% and 26.7%). Amyloid-related imaging abnormalities-hemorrhage (ARIA-H) were similar (12.5% ABvac40; 15.0% placebo), with no ARIA-edema (ARIA-E) or meningoencephalomyelitis. ABvac40 induced a specific, sustained immune response in plasma, with detectable antibodies in CSF. Discussion: These findings support further investigation of ABvac40 as a potential disease-modifying therapy. Clinical trial registration number: NCT03461276 (ClinicalTrials.gov) HIGHLIGHTS: ABvac40 was safe and well-tolerated in early-stage Alzheimer's disease patients. No amyloid-related imaging abnormalities-edema (ARIA-E) or encephalitis observed; ARIA-hemorrhage (ARIA-H) rates were similar across groups. Specific, sustained immune response to ABvac40 in plasma, with cerebrospinal fluid (CSF) antibody penetration. Cognitive scales and magnetic resonance imaging (MRI) volumetric data favored ABvac40 over placebo. Results support further development of ABvac40 as a disease-modifying therapy.
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Endometrial cancer progression driven by PTEN-deficiency requires miR-424(322)~503
(Springer Nature, 2025-10) Vidal Sabanés, Maria; Bonifaci, Núria; Navaridas, Raúl; Egea Navarro, Joaquim; Encinas Martín, Mario; Rodriguez-Barrueco, Ruth; Silva, Jose M.; Matias-Guiu, Xavier; Llobet Navas, David; Dolcet Roca, Xavier
Endometrial cancer is the most frequent type of cancer in the female reproductive tract. Loss-of-function alterations in PTEN, leading to enhanced PI3K/AKT activation, are among the most frequent molecular alterations in endometrial cancer. Increased PI3K/AKT signaling resulting from PTEN loss promotes cellular proliferation and confers resistance to TGFβ-mediated apoptosis, a key regulator of endometrial homeostasis. In this study, we have analyzed the role of miRNAs in driving these altered cellular responses. A comprehensive transcriptomic analysis of miRNA expression revealed the upregulation of several miRNAs caused by PTEN deficiency and/or TGFβ stimulation. The miR-424(322)~503 cluster drew our attention due to its involvement in regulating apoptosis and proliferation. However, miR-424(322)~503 cluster has a paradoxical role in cancer, exhibiting either oncogenic and tumor suppressive functions depending on cell type or context. To ascertain the function of miR-424(322)~503 in endometrial carcinogenesis caused by PTEN deficiency, we generated a double Pten/miR-424(322)~503 knock-out mice. We demonstrate that loss of miR-424(322)~503 impairs proliferation of both wild type or Pten deficient endometrial organoids by interfering with growth factor and PI3K/AKT signaling. Furthermore, the absence of miR-424(322)~503 restores TGFβ-induced apoptosis, which is otherwise compromised by PTEN deficiency. In vivo, Pten/miR-424(322)~503 knock-out mice exhibit reduced endometrial cancer progression compared to Pten deficient mice through a cell-autonomous mechanism.
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Open Access
Explorando la relación entre ansiedad estado, género y rendimiento académico en estudiantes de educación secundaria
(Universidad de Navarra, 2025) Garcia-Blanc, Núria; Gomis Cañellas, Raquel; Ros Morente, Agnès; Filella Guiu, Gemma
Se analiza la relación entre ansiedad estado y rendimiento académico en 344 estudiantes de educación secundaria españoles (M= 13,66; DT= 1,184), explorando el rol moderador del género. La muestra incluyó una proporción equilibrada de chicos (49%) y de chicas (51%), procedentes de dos centros educativos, uno público y otro concertado. Se emplearon pruebas U de Mann-Whitney y análisis de regresión lineal para analizar las diferencias entre géneros y evaluar los efectos directos e interactivos. Para ello, se utilizó la escala de ansiedad estado del STAI y las calificaciones medias. Los resultados mostraron una relación negativa significativa entre la ansiedad estado y el rendimiento académico, así como niveles significativamente más altos de ansiedad estado en las chicas. Además, se observó un efecto directo e interactivo del género y la ansiedad en el rendimiento académico. Estos hallazgos destacan la importancia de abordar la ansiedad en la educación secundaria mediante propuestas centradas en el desarrollo de competencias emocionales.
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Open Access
Self-reported mental distress in the United States: a Bayesian analysis of the spatial structure over the COVID-19 pandemic across age groups
(BMC, 2025) Comas Rodríguez, Carles; Martínez, Albert; Blanch Plana, Angel
Background The COVID-19 had an outstanding impact on well-being and mental health, which might have elicited geographical variations over time. This study examines the eventual impact of COVID-19 on self-reported mental distress in the mainland USA. Aims There were two main aims. First, to evaluate the pre-pandemic (2019; n = 412, 597) and post-pandemic (2021; n = 440, 075) mental distress spatial distribution. Second, to contrast spatial data across three age groups, young (18–44 years), middle-aged (45–65 years), and old (older than 65 years). Method We considered a the Bayesian modified Besag–York–Molliè (BYM2) model, which is a Bayesian hierarchical model. Mental distress was the response variable function of age group, year and spatially structured and unstructured effects. Results The main findings indicate a positive spatial dependence between states of general mental distress before and after the COVID-19 and across age groups with substantial unstructured component. Moreover, younger individuals reported higher levels of mental distress and suffered the major worsening due to the pandemic. Conclusions COVID-19 had a detrimental impact on mental health across the population, with consistent evidence of positive spatial dependence across states. Notably, young adults emerged as particularly vulnerable, exhibiting concerning levels of mental distress problems and being more sensitive to the effects of the pandemic. Henceforth, young adults might require specific tailored public health policies in eventual major pandemic events.
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The roles of general mattering, anti-mattering, psychological distress, and mistake tolerance in teacher turnover: insights from Chinese educational settings
(Springer Nature, 2025) Yao, Wenjing; Cheng, Aihua; Cao, Cui-Hong; Chen, I-Hua; Wei, Xiaoxia; Malas, Olga
Despite increasing recognition of general mattering (GM) and anti-mattering (AM) as crucial psychological constructs in workplace well-being, gaps exist in understanding their mechanisms in educational settings, and longitudinal evidence examining these relationships is also lacking. This two-wave longitudinal study explores how GM and AM influence psychological distress (PD) and turnover intentions (TI) among Chinese teachers, while examining the moderating role of mistake tolerance (MT) on these relationships. Data were collected at two time points: February and March 2024 (Time 1), followed by a second survey after a four-month interval (Time 2), with participants including 812 school teachers in China. Structural equation modeling (SEM) with bootstrapping techniques was used to analyze the mediation pathways from GM and AM to TI via PD. Results reveal that PD mediates the relationship between GM, AM, and TI, with higher GM linked to lower PD and TI, whereas AM was associated with increased PD and TI; additionally, MT moderated the GM-PD relationship such that in low-MT settings, lower GM increased PD, but this effect was absent in high-MT settings. This study confirms GM and AM as distinct constructs, with AM emerging as a unique psychological experience rather than merely the absence of GM, and introducing MT as a moderator highlights managerial support’s role in reducing turnover, while its longitudinal design offers insights for improving teacher well-being.