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Alzheimer’s disease (AD) has become a common disease of the elderly for which no cure currently exists. After over 30 years of intensive research, we have gained extensive knowledge of the genetic and molecular factors involved and their interplay in disease. These findings suggest that different subgroups of AD may exist. Not only are we starting to treat autosomal dominant cases differently from sporadic cases, but we could be observing different underlying pathological mechanisms related to the amyloid cascade hypothesis, immune dysfunction, and a tau-dependent pathology. Genetic, molecular, and, more recently, multi-omic evidence support each of these scenarios, which are highly interconnected but can also point to the different subgroups of AD. The identification of the pathologic triggers and order of events in the disease processes are key to the design of treatments and therapies. Prevention and treatment of AD cannot be attempted using a single approach; different therapeutic strategies at specific disease stages may be appropriate. For successful prevention and treatment, biomarker assays must be designed so that patients can be more accurately monitored at specific points during the course of the disease and potential treatment. In addition, to advance the development of therapeutic drugs, models that better mimic the complexity of the human brain are needed; there have been several advances in this arena. Here, we review significant, recent developments in genetics, omics, and molecular studies that have contributed to the understanding of this disease. We also discuss the implications that these contributions have on medicine.

The aim of the present study was to develop and validate a short form of the Genderism and Transphobia Scale and assess adolescents' attitudes toward transpeople. A total of 800 Spanish adolescents aged between 14 and 18 years (50.70% girls, 49.30% boys) completed the Spanish version of the scale and other related questionnaires. The short form of the scale is composed of 12 items clustered into two factors (Transphobia/Genderism and Gender Bashing) that explain 54.22% of the variance. All the items showed good discriminating power, and the present scale demonstrated adequate reliability and validity. In the study, boys exhibited significantly more negative attitudes toward transpeople than girls did, both in the affective/cognitive dimension (Transphobia/Genderism) and in the behavioral dimension (Gender Bashing). Moreover, adolescents showed significantly more negative attitudes toward gender-nonconforming men than toward gender-nonconforming women. These results are discussed in terms of their relevance to the maintenance of discriminatory attitudes toward sexual diversity.

Background Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant carriers also exhibit differential CSF TREM2 levels. TREM2 has three different alternative transcripts, but most of the functional studies only model the longest transcript. No studies have analyzed TREM2 expression levels or alternative splicing in brains from AD and cognitively normal individuals. We wanted to determine whether there was differential expression of TREM2 in sporadic-AD cases versus AD- TREM2 carriers vs sex- and aged-matched normal controls; and if this differential expression was due to a particular TREM2 transcript. Methods We analyzed RNA-Seq data from parietal lobe brain tissue from AD cases with TREM2 variants ( n  = 33), AD cases ( n  = 195) and healthy controls ( n  = 118), from three independent datasets using Kallisto and the R package tximport to determine the read count for each transcript and quantified transcript abundance as transcripts per million. Results The three TREM2 transcripts were expressed in brain cortex in the three datasets. We demonstrate for the first time that the transcript that lacks the transmembrane domain and encodes a soluble form of TREM2 (sTREM2) has an expression level around 60% of the canonical transcript, suggesting that around 25% of the sTREM2 protein levels could be explained by this transcript. We did not observe a difference in the overall TREM2 expression level between cases and controls. However, the isoform which lacks the 5′ exon, but includes the transmembrane domain, was significantly lower in TREM2 - p.R62H carriers than in AD cases ( p  = 0.007). Conclusion Using bulk RNA-Seq data from three different cohorts, we were able to quantify the expression level of the three TREM2 transcripts, demonstrating: (1) all three transcripts of them are highly expressed in the human cortex, (2) that up to 25% of the sTREM2 may be due to the expression of a specific isoform and not TREM2 cleavage; and (3) that TREM2 risk variants do not affect expression levels, suggesting that the effect of the TREM2 variants on CSF levels occurs at post-transcriptional level.

The homology and evolution of the archosaur ankle is a controversial topic that has been deeply studied using evidence from both extinct and extant taxa. In early stem archosaurs, the astragalus and calcaneum form the ancestral proximal tarsus and a single ossification composes the centrale series. In more recent stem archosaurs, the centrale is incorporated to the proximal row of tarsals laterally contacting the astragalus. This bone is subsequently lost as an independent ossification before the last common ancestor of birds and crocodilians, but the evolutionary fate of this element remains mostly unexplored. Here, we integrate embryological and palaeontological data with morphogeometric analyses to test the hypothesis of loss of the centrale or, alternatively, its incorporation into the archosaurian astragalus. Our results support the latter hypothesis, indicating that the astragalus developed ancestrally from two ossification centres in stem archosaurs and that the supposed tibiale of bird embryos represents a centrale. This conclusion agrees with previous embryological studies that concluded that the tibiale never develops in diapsids.

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

Adolescence, a period of physical, social, cognitive and emotional development, represents a target population for sexual health promotion and education when it comes to achieving the 2030 Agenda goals for sustainable and equitable societies. The aim of this study is to provide an overview of what is known about the dissemination and effectiveness of sex education programs and thereby to inform better public policy making in this area. Methodology: We carried out a systematic review based on international scientific literature, in which only peer-reviewed papers were included. To identify reviews, we carried out an electronic search of the Cochrane Database Reviews, ERIC, Web of Science, PubMed, Medline, Scopus and PsycINFO. This paper provides a narrative review of reviews of the literature from 2015 to 2020. Results: 20 reviews met the inclusion criteria (10 in school settings, 9 using digital platforms and 1 blended learning program): they focused mainly on reducing risk behaviors (e.g., VIH/STIs and unwanted pregnancies), whilst obviating themes such as desire and pleasure, which were not included in outcome evaluations. The reviews with the lowest risk of bias are those carried out in school settings and are the ones that most question the effectiveness of sex education programs. Whilst the reviews of digital platforms and blended learning show greater effectiveness in terms of promoting sexual and reproductive health in adolescents (ASRH), they nevertheless also include greater risks of bias. Conclusion: A more rigorous assessment of the effectiveness of sexual education programs is necessary, especially regarding the opportunities offered by new technologies, which may lead to more cost-effective interventions than with in-person programs. Moreover, blended learning programs offer a promising way forward, as they combine the best of face-to-face and digital interventions, and may provide an excellent tool in the new context of the COVID-19 pandemic.

Phylogeographical studies can reveal hidden patterns in the evolutionary history of species. Comparative analyses of closely related species can further help disentangle the relative contributions of processes responsible for such patterns. In this work, the phylogeography of two aristeid species, Aristeus antennatus and Aristaeomorpha foliacea, was compared through multiple genetic markers. These marine shrimp species are of high commercial importance, and are exploited in the Mediterranean Sea (MED) and in Mozambique Channel (MOZ) where they occur in partial sympatry. Aristeus antennatus (N = 50) from Western and Eastern Mediterranean (WM and EM, respectively), Atlantic Ocean (AO) and MOZ, and Aristaeomorpha foliacea (N = 40) from WM, EM, MOZ North-Western Australia (AUS) were analyzed with two nuclear genes (PEPCK and NaK) and one mitochondrial (COI) gene. Within the study area differences were found between the two species in their phylogeographical patterns, suggesting distinct responses to environmental changes. Monophyly of Aristeus antennatus was found across its distributional range. This pattern contrasted by a deep evolutionary split within Aristaeomorpha foliacea where genetic diversity followed geography distinguishing MED-MOZ and AUS. We propose that the AUS lineage of A. foliacea warrants consideration as a distinct species, with consequent implications in systematics and resource management.

Ageing is accompanied by gradual biological and cognitive changes that increase vulnerability to chronic diseases and neurodegenerative conditions. As populations age, dementia prevalence continues to rise, highlighting the need for earlier detection and personalised prevention strategies. Against this background, the COMFORTage project, funded by Horizon Europe, brings together a multidisciplinary consortium across 12 countries to advance innovative, scalable solutions for dementia care. By integrating digital platforms, biomarker research, and precision medicine, COMFORTage seeks to develop artificial intelligence (AI)-driven tools that support more precise and adaptive interventions. Central to this effort are the Virtualized AI-Based Healthcare Platform and Patient Digital Twins, which enable personalised monitoring and decision support. Within this framework, Pilot 3 at Ace Alzheimer Center Barcelona focuses on individuals with mild cognitive impairment and mild Alzheimer's disease dementia, evaluating the effects of cognitive and functional stimulation and contributing multimodal data to optimise the AI platform. Pilot 3 is a randomised, open-label study involving retrospective and prospective datasets. Participants undergo clinical, genetic, neuropsychological, cerebrospinal fluid (CSF) and plasma biomarker assessments, magnetic resonance imaging (MRI), and spontaneous speech analysis. The primary outcomes assess cognitive decline using composite scores from the Neuropsychological Battery used in Ace (NBACE), targeting attention, memory, visuospatial/perceptual functions, executive functions, and language, over a two-year follow-up. Three digital platforms provided by the consortium will be used as cognitive and functional stimulation tools for participants. The intervention's effects on cognitive decline will be evaluated through changes in NBACE composite scores. Secondary objectives include assessing impacts on physical, psychological, social, and functional well-being; examining associations between biological variables and cognitive changes; and analyzing spontaneous speech as a remote, scalable proxy for cognitive status. Findings from Pilot 3 will contribute to COMFORTage's broader mission, offering critical insights into the scalability and real-world implementation of AI-powered dementia care solutions. This integrated approach highlights the potential of precision medicine and advanced digital tools to elevate global standards in dementia management. identifier NCT07031167.

The blue and red shrimp Aristeus antenantus supports an important commercial fishery in the Western Mediterranean, adjacent Atlantic waters and Mozambique Channel (western Indian Ocean). This study investigates its genetic structure by examining a total of 506 individuals from Mediterranean, Atlantic and Indian Ocean locations. In order to identify putative genetic stocks, sequences from 16S rDNA (546 bp) and COI (514 bp) genes were used. Genetic diversity, estimated by haplotypic and nucleotidic diversity, was lower in the Western Mediterranean than in samples from other locations. The high haplotypic diversity of the Eastern Mediterranean, Atlantic and Indian Ocean samples reflects the occurrence of a number of private haplotypes, which are also responsible for significant genetic divergence between these samples and the Western Mediterranean ones. The analysis of mismatch distributions, neutrality tests, and star-like patterns present in the network of haplotypes provided consistent inference of past population expansion in the Western Mediterranean, Atlantic and Mozambique Channel regions. Our study provides the first evidence of genetic structuring in A. antennatus across its distributional range.

Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer’s disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer’s disease, Parkinson’s disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases. Yang et al. generated a genomic atlas of protein levels in brain, cerebrospinal fluid and plasma and used human genetics approaches to identify proteins implicated in neurological diseases as well as druggable targets.