https://repositorio.fleni.org.ar/xmlui/handle/123456789/809 2026-04-05T18:11:36Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1484 Capacity building in dementia research: insights from the World Young Leaders in Dementia Morello-García, Florentina; Corvalán, Nicolás; Llibre-Guerra, Jorge; Arruabarrena, Micaela; Clarens, María Florencia; Keller, Greta; De Los Santos, Loana; Martin, María Eugenia; Schaffer Aguzzoli, Cristiano; Allegri, Ricardo Francisco; Amaral, Livia; Ardohain Cristalli, Carolina; Bellaver, Bruna; Ngozi Best, Merci; Bloomquist, Madeleine; Chen, Kevin; Surace, Ezequiel Ignacio; Wilks, Hannah; Zimmer, Eduardo; Crivelli, Lucía; Hernández, Micaela Anahí; Magrath Guimet, Nahuel Early-career researchers from low- and middle-income countries face systemic barriers to professional development and leadership growth. This article presents results from an initiative led by the World Young Leaders in Dementia (WYLD), including a leadership-focused session at the Alzheimer's Association International Conference 2024 and a global survey completed by 130 dementia researchers from 17 countries. The survey explored five capacity-building domains critical for leadership development. Over half of the survey respondents stated that scientific research in their country was not prioritized in public policy. Additionally, only 39% report holding full-time academic positions. The most cited challenges included lack of funding sources, training opportunities, and physical workspace. These findings highlight the urgent need to invest in research, training, and infrastructure to support future scientific leaders. As dementia incidence rises, prioritizing capacity building is essential to ensure global equity in research. HIGHLIGHTS: Early-career dementia researchers face major barriers, especially in LMICs. A networking session and a global survey explored capacity-building needs in dementia research. Key obstacles: lack of funding, training, workspace, and protected research time. Leadership development is a critical component of sustainable research capacity. 2025-12-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1478 Thyrotropin Modulates Calcium Handling and Contractility in Adult Cardiac Myocytes Sepúlveda, Marisa; Racioppi, Florencia; Burgos, Juan Ignacio; Murillo, Alexandra; Fernandez-Ruocco, Julieta; Gonano, Luis; Neiman, Gabriel; Miriuka, Santiago Gabriel; Fellet, Andrea; Casis, Oscar; Medei, Emiliano; Colareda, German; Vila Petroff, Martín Hypothyroidism is an independent risk factor for cardiovascular disease and, if chronically sustained, leads to myocardial contractile dysfunction resulting in heart failure. However, the subcellular mechanisms underlying contractile dysfunction are not completely understood. It has been suggested that abnormal gene expression in the myocardium triggered by decreased thyroid hormone plasma levels reduces the expression of sarco-/endoplasmic reticulum calcium ion (Ca2+) adenosine triphosphatase (SERCA), resulting in slower sarcoplasmic reticulum (SR) Ca2+ uptake, a decrease in SR Ca2+ content and reduced SR Ca2+ release that mediates contractile dysfunction [1]. However, in addition to the decrease in thyroid hormones, hypothyroidism is characterised by increased thyrotropin (TSH) levels. Interestingly, subclinical hypothyroidism, which is defined by increased TSH with normal T3 and T4 levels, is also associated with altered contractile dysfunction [2], suggesting that TSH could contribute to reduced contractility observed in hypothyroidism. However, whether and how TSH impacts adult cardiac myocyte contractile function has never been addressed. This study aims to investigate whether TSH affects Ca2+ dynamics, Ca2+ handling protein expression, and contractile function in adult rat cardiac myocytes and in human-induced pluripotent stem cell-derived cardiac myocytes. 2025-10-15T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1463 Comparative diagnostic performance of artificial intelligence models in structural MRI for schizophrenia: A systematic review and meta-analysis Kotochinsky, Martin; Oliveira Fonseca, Pandora Eloa; Ramirez Lopera, Veronica; Mora, Laura; Wellgner Fernandes Oliveira, Amador; Cesar Teixeira Sirena, Eduardo; Bandeira de Melo Guimarães, Felipe; Lahitou Herlyn, Delfina; Norbu Sherpa, Nima; Gonzalez Lezana, Andrea; Pardini Fagundes, Thales Introduction: Timely diagnosis of schizophrenia is essential to ensure prompt treatment initiation and adherence. Structural magnetic resonance imaging (sMRI), when combined with artificial intelligence (AI), offers a promising avenue to enhance diagnostic accuracy. However, its performance and clinical use is a matter of debate. Methods: PubMed, Embase, and Cochrane databases were searched for studies using AI models with sMRI to diagnose schizophrenia in adults. Eligible models encompass traditional machine learning methods and deep learning (DL) architectures, utilizing diverse neuroanatomical inputs, including gray matter (GM) features and whole-brain (WB) structural data. The outcomes of interest were diagnostic performance metrics as: sensitivity (SE), specificity (SP), area under the curve (AUC). Results: A total of 16 studies were included, comprising 3601 participants. Overall pooled SE and SP were 0.76 (95 % CI: 0.71-0.80) and 0.78 (95 % CI: 0.73-0.82), respectively. When compared, DL models outperformed Support Vector Machine (SVM), achieving higher SP of 0.83 (95 % CI: 0.80-0.86) vs. 0.78 (95 % CI: 0.72-0.83), and AUC of 0.892 (95 % CI: 0.81-0.90) vs. 0.782 (95 % CI: 0.70-0.82). WB input models also outperformed GM performance, with SP of 0.86 (95 % CI: 0.78-0.92) vs. 0.80 (95 % CI: 0.73-0.85), and AUC of 0.89 (95 % CI: 0.70-0.93) vs. 0.816 (95 % CI: 0.71-0.84). Conclusion: AI models using sMRI show promising but provisional diagnostic performance for schizophrenia. Across studies, DL architectures and WB inputs generally achieved higher specificity and AUC than SVM and GM features. Prospective, multi-site external validation cohorts are needed before routine clinical implementation. 2025-11-04T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1462 Clinical and functional evidence supporting the pathogenicity of the novel PSEN1 p.R358P variant in early-onset Alzheimer's disease García Chialva, Diego; Itzcovich, Tatiana; Cifarelli, Diego; Apecetche, Manuela; Chrem Méndez, Patricio; Magrath Guimet, Nahuel; Vázquez, Silvia; Bérgamo, Yanina; Allegri, Ricardo Francisco; Marazita, Mariela; Sevlever, Gustavo Emilio; Isaja, Luciana; Surace, Ezequiel Ignacio; Romorini, Leonardo BackgroundPathogenic variants in PSEN1, PSEN2, or AβPP cause early-onset Alzheimer's disease (EOAD). Several novel variants remain of uncertain significance (VUS) due to limited evidence. The PSEN1 p.R358P variant has not been previously characterized or reported in EOAD cases.ObjectiveTo determine the pathogenicity of the PSEN1 p.R358P variant in a patient with EOAD and assess its effect on amyloid-β (Aβ) processing using a human cellular model.MethodsWe present the case of a 62-year-old female of Western European descent with memory impairment starting at 59 and a positive family history of Alzheimer's disease (AD). To evaluate the variant, a PSEN1 knockout HEK293T line was generated using CRISPR/Cas9. Cells were co-transfected with AβPP and either wild-type or mutant PSEN1, and Aβ42/Aβ40 levels were measured by ELISA in culture supernatants.ResultsThe proband exhibited multidomain cognitive impairment and imaging biomarkers (PiB-PET and FDG-PET) consistent with AD. Whole-exome sequencing revealed a PSEN1 (NM_000021.4:c.1073G > C:p.Arg358Pro) variant, classified as VUS by ACMG guidelines, together with a SORL1 p.G1536D variant and APOE ε4/ε4 genotype. Cells expressing PSEN1 p.R358P showed an increased Aβ42/Aβ40 ratio compared to wild-type, mainly due to reduced Aβ40 levels. This profile partially mimicked the pathogenic PSEN1 p.A246E variant. In silico analyses predicted deleterious effects for PSEN1 p.R358P.ConclusionsOur results support a likely pathogenic role for the PSEN1 p.R358P variant in EOAD. Nonetheless, in the absence of segregation data, the variant should be considered a hot VUS. 2025-11-06T00:00:00Z