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Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. Nowadays, these two groups present distinct genetic diversity and group-specific variation linked to pathogens. We propose differing hydrology patterns and effectiveness of geographic barriers have modulated the intra-group connectivity and structure of bald and black uakari populations. With this work we have explored the effects of the Amazon rainforests dynamism on wild primates genetics and increased the representation of platyrrhine genomes, thus opening the door to future research on the complexity and diversity of primate genomics.

Previous research on children's knowledge about the mind has primarily focused on their comprehension of false beliefs, leaving the conceptualization of thoughts and thinking less explored. To address this gap, we developed a new assessment tool, the interview about the mind (IaM), to assess children's understanding of the mind. Two studies involving Polish preschool and early school-aged children were conducted to assess the validity and reliability of the tool: a cross-sectional study with 212 preschoolers aged three to 6 years (106 boys, M = 59 months) followed by a longitudinal study with approximately 200 children (110 boys) assessed at ages 5.5, 6.5, and 7.5 years. We found that the IaM possesses robust psychometric properties and a one-factor structure. Younger children recognize that thoughts are imperceptible to the senses and identified the mind's location as the head. Older children exhibited difficulties with analogical or abstract definitions of thoughts. As expected, a linear developmental trajectory was evident from ages 5.5-7.5, with children's language abilities showing a positive correlation with IaM scores. Future research should explore the relationship between knowledge about the mind and theory of mind (ToM), as well as cross-cultural differences in children's mind conceptualization.

This article presents a new algorithm for recognizing defects and discontinuities. It is a neural classification algorithm of the SVM class used for the vision system in the technological sequence. At the basis of the used method of Support Vector Machines (SVM) lies the concept of decision-making space, which is divided by building boundaries separating objects with different class affiliation, that is, defects and discontinuities. The Support Vector Machines method is supposed to perform classification tasks by constructing in a multidimensional space hyperplane separating cases belonging to different classes.

Abstract Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. Nowadays, these two groups present distinct genetic diversity and group-specific variation linked to pathogens. We propose differing hydrology patterns and effectiveness of geographic barriers have modulated the intra-group connectivity and structure of bald and black uakari populations. With this work we have explored the effects of the Amazon rainforest’s dynamism on wild primates’ genetics and increased the representation of platyrrhine genomes, thus opening the door to future research on the complexity and diversity of primate genomics.

Abstract Background Phenotypic data comparison is essential for disease association studies, patient stratification, and genotype–phenotype correlation analysis. To support these efforts, the Global Alliance for Genomics and Health (GA4GH) established Phenopackets v2 and Beacon v2 standards for storing, sharing, and discovering genomic and phenotypic data. These standards provide a consistent framework for organizing biological data, simplifying their transformation into computer-friendly formats. However, matching participants using GA4GH-based formats remains challenging, as current methods are not fully compatible, limiting their effectiveness. Results Here, we introduce Pheno-Ranker, an open-source software toolkit for individual-level comparison of phenotypic data. As input, it accepts JSON/YAML data exchange formats from Beacon v2 and Phenopackets v2 data models, as well as any data structure encoded in JSON, YAML, or CSV formats. Internally, the hierarchical data structure is flattened to one dimension and then transformed through one-hot encoding. This allows for efficient pairwise (all-to-all) comparisons within cohorts or for matching of a patient’s profile in cohorts. Users have the flexibility to refine their comparisons by including or excluding terms, applying weights to variables, and obtaining statistical significance through Z-scores and p-values. The output consists of text files, which can be further analyzed using unsupervised learning techniques, such as clustering or multidimensional scaling (MDS), and with graph analytics. Pheno-Ranker’s performance has been validated with simulated and synthetic data, showing its accuracy, robustness, and efficiency across various health data scenarios. A real data use case from the PRECISESADS study highlights its practical utility in clinical research. Conclusions Pheno-Ranker is a user-friendly, lightweight software for semantic similarity analysis of phenotypic data in Beacon v2 and Phenopackets v2 formats, extendable to other data types. It enables the comparison of a wide range of variables beyond HPO or OMIM terms while preserving full context. The software is designed as a command-line tool with additional utilities for CSV import, data simulation, summary statistics plotting, and QR code generation. For interactive analysis, it also includes a web-based user interface built with R Shiny. Links to the online documentation, including a Google Colab tutorial, and the tool’s source code are available on the project home page: https://github.com/CNAG-Biomedical-Informatics/pheno-ranker .

Abstract Background Critical illness is associated with an altered gut microbiota, yet its association with poor outcomes remains unclear. This study evaluates the early gut microbiota diversity changes in intensive care unit patients and its association with mortality. Additionally, it explores fecal pH as a potential biomarker for these changes. Methods In this prospective observational cohort study, fecal samples were collected at two time points: S1, the first stool passed upon intensive care unit admission, and S2, the first stool passed at least 24 h after S1. Full-length 16S rRNA gene sequencing was performed for gut microbiota analysis, with α-diversity measured using the Shannon index. Bayesian joint models were used to estimate the association between time-varying changes in gut microbiota diversity and 60-day mortality, as well as the association between daily changes in stool pH and in diversity. Results Twenty-four of 96 patients overall died during follow-up. Daily Shannon index decreased on average by −0.1 points [95% Credible Intervals (CrI) −0.20 to −0.10]. Every point decrease in Shannon index was associated with a 1.99-fold increase in the hazard of death (95% CrI, 1.04 to 4.51). Time-varying fecal pH levels were not associated with changes in Shannon index. Conclusions Gut microbiota diversity decreased over time, associated with increased mortality. Fecal pH is an unreliable marker of gut microbiota change. Future studies on gut microbiota and related biomarkers should focus on the initial days in the intensive care unit to detect and mitigate a decline in gut microbiota diversity.

Abstract Deep single-cell multi-omic profiling offers a promising approach to understand and overcome drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML). Here, we combine single-cell ex vivo drug profiling (pharmacoscopy) with single-cell and bulk DNA, RNA, and protein analyses, alongside clinical data from 21 rrAML patients. Unsupervised data integration reveals reduced ex vivo response to the Bcl-2 inhibitor venetoclax (VEN) in patients treated with both a hypomethylating agent (HMA) and VEN, compared to those pre-exposed to chemotherapy or HMA alone. Integrative analysis identifies both known and unreported mechanisms of innate and treatment-related VEN resistance and suggests alternative treatments, like targeting increased proliferation with the PLK inhibitor volasertib. Additionally, high CD36 expression in VEN-resistant blasts associates with sensitivity to CD36-targeted antibody treatment ex vivo. This study demonstrates how single-cell multi-omic profiling can uncover drug resistance mechanisms and treatment vulnerabilities, providing a valuable resource for future AML research.

Abstract Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. Recent studies have revealed that all types of DNA glycosylases repair base lesions less efficiently within nucleosomes, and their repair activity is highly depended on the lesion’s location within the nucleosome. To reveal the underlying molecular mechanism of this phenomenon, we determine the 3.1 Å cryo-EM structure of human 8-oxoguanine-DNA glycosylase 1 (hOGG1) bound to a nucleosome core particle (NCP) containing a common oxidative base lesion, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). Our structural analysis shows that hOGG1 can recognize and flip 8-oxodGuo even within NCPs; however, the interaction between 8-oxodGuo and hOGG1 in a NCP context is weaker than in free DNA due to competition for nucleosomal DNA by the histones. Binding of OGG1 and the flipping of 8-oxodGuo by hOGG1 leads to a partial detachment of DNA from the histone core and a ratchet-like inward movement of nucleosomal DNA. Our findings provide insights into how the dynamic structure of nucleosomes modulate the activity of repair enzymes within chromatin.

There is a scarcity of research into the relationship between speech perception and production from a multilingual perspective. The present exploratory study investigates longitudinally the acquisition of rhotic sounds in 24 adolescent learners who have the same language repertoires (English, German, Polish), with English being their L2, and German and Polish their L1 or L3. The design involved a forced-choice goodness task (for perception) and a delayed repetition task (for production) administered in both L2 and L3 at two testing times. The overall results show better performance in perception than production of L2/L3 rhotics at both testing points, although the relationship between the two domains was modulated by the L1 background and universal learnability of the target rhotics. A major effect of language proficiency was found, as overall a stronger link between the two modalities was found for the L2 than the L3 of the learner groups. However, detailed analyses demonstrate different types of perception-production link for individual learners over time.

Abstract A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

Abstract Background Promoting older workers’ health in the context of increasing labor force participation and skill shortages is crucial. Examining job resource profiles offers a promising approach to understanding how to promote and maintain the health of older workers within the workplace. However, it is unclear how different job resources interact within distinct worker subgroups. Thus, this study explores the association between the job resource profiles of distinct subgroups and various health indicators among older workers in Europe. Methods Data from 4,079 older workers (age range: 50–60 years, 57% female) from waves 6 and 8 of the Survey of Health, Ageing and Retirement in Europe (SHARE) were analyzed. Latent profile analysis was employed to identify distinct job resource profiles using social support, recognition, job promotion, autonomy, and development opportunities. Associations between these profiles and various health indicators were examined, alongside the sociodemographic and socioeconomic characteristics associated with each profile. Results Four distinct job resource profiles emerged: (I) average job resource workers (n = 2170, 53%), (II) high social job resource workers (n = 983, 24%), (III) low job resource workers (n = 538, 13%), and (IV) autonomous decision-making workers (n = 388, 10%). Workers in the (II) high social job resource profile had the highest socioeconomic status and reported the best self-perceived health, lowest depressive symptoms, and fewest limitations and chronic diseases. Conversely, workers in the (III) low job resource profile had the second-lowest socioeconomic status and reported the poorest health outcomes. Surprisingly, older workers with high autonomy (profile IV) had the lowest socioeconomic status and the second worst self-perceived health. This may be because they perceive themselves as autonomous while lacking support and recognition. Conclusion There is wide variation in the level and composition of resources available to older workers in the workplace. The most vulnerable subgroups, such as low job resource workers (profile III) and autonomous decision-making workers (profile IV), could benefit from tailored workplace health promotion interventions, such as support from supervisors or peers. Strengthening older workers’ job resources, including social support and recognition, can improve their health and contribute to them remaining in the workforce.

This study investigates sources of phonological cross-linguistic influence (CLI) at the initial stages of third language (L3) acquisition in light of the predictions of the second language (L2) Status Factor Model, the Typological Primacy Model, the Cumulative Enhancement Model, the Linguistic Proximity Model and the Scalpel Model. The productions of L3 rhotic sounds, /w/ and final obstruent devoicing, elicited in a delayed repetition task, were analysed auditorily in two groups of adolescent instructed learners with L1-German--L2-English--L3-Polish and L1-Polish--L2-English--L3-German language backgrounds. The results showed that dominant articulatory routines from the L1 play an important role in determining the source(s) of phonological CLI in the initial stages of L3 acquisition, at least in a learning constellation when L2 articulations have not been mastered yet in a consistently target-like manner. Based on loglinear and multiple correspondence analyses, the sources of phonological CLI were found in this study to vary feature-by-feature, thus giving some support to the Linguistic Proximity Model and the Scalpel Model. However, the high inter- and intra-individual variation that was found is so far not accounted for by any of the existing models.

The university curriculum plays a role in motivating students to take up research. This 2-year action research explored the curriculum in English for Academic Purposes (EAP) and its influence on student further engagement in research work. The data were collected from University Master's students through two questionnaires given to them before and after studying the course. An explanatory framework for the course characteristics that affected students' attitudes towards research focused upon the students' profile (the students' age, gender, major and language proficiency), career orientation and research orientation. The shift in students' attitudes reinforced the complexity of factors that influenced their motivation to take up research after graduation. The authors draw a conclusion that future interventions to address issues with the Academic English course to raise the interest of University students should deal with restructuring the course in a way that the student should have more contact hours. The analysis of learning materials designed for the EAP course shows that most of them introduce students to theory- and research-informed perspectives and guide them in putting theory to use in real-world contexts which would be impossible in 30 contact hours as in the analysed case. Moreover, it should be linked to the students' school practice and their small-scale research in real classroom settings.

IntroductionThe pedunculopontine nucleus (PPN) plays a role in coordinating complex behaviors and adapting to changing environmental conditions. The specific role of cholinergic neurons in PPN function is not well understood, but their ascending connectivity with basal ganglia and thalamus suggests involvement in adaptive functions.MethodsWe used a chemogenetic approach in ChAT::Cre rats to explore the specific contribution of PPN cholinergic neurons to behavioral flexibility, focusing on the adaptation to shifting reward contingencies in a Reversal Learning Task. Rats were first trained in a non-probabilistic reversal learning task, followed by a probabilistic phase to challenge their adaptive strategies under varying reward conditions.ResultsMotor functions were evaluated to confirm that behavioral observations were not confounded by motor deficits. We found that inhibition of PPN cholinergic neurons did not affect performance in the non-probabilistic condition but significantly altered the rats’ ability to adapt to the probabilistic condition. Under chemogenetic inhibition, the rats showed a marked deficiency in utilizing previous trial outcomes for decision-making and an increased sensitivity to negative outcomes. Logistic regression and Q-learning models revealed that suppression of PPN cholinergic activity impaired the adaptation of decision-making strategies.DiscussionOur results highlight the role of PPN cholinergic neurons in dynamically updating action-outcome expectations and adapting to new contingencies. The observed impairments in decision-making under PPN cholinergic inhibition align with cognitive deficits associated with cholinergic dysfunction in neurodegenerative disorders. These findings suggest that cholinergic neurons in the PPN are essential for maximizing rewards through the flexible updating of behavioral strategies.

Objectives Telemonitoring (TM) of home non-invasive ventilation (NIV) has been shown to facilitate home/outpatient therapy set-up. However, the impact of long-term TM on therapy dropouts, compliance and leak control has not yet been clearly determined. This study evaluated whether the NIV dropout rate was reduced by TM combined with remote patient support compared with a non-telemonitoring (NTM) pathway.Design Retrospective cohort study.Setting Data were obtained from all agencies of a single home care provider in France.Participants Adults with chronic respiratory failure (n=659) who started nocturnal NIV between January 2017 and December 2019 and had ≥8 days of NIV therapy (51% male; mean age 68.5±13.8 years; 35.5% on long-term oxygen therapy) were included. The TM group included 275 patients who spent ≥80% of the follow-up using TM, and the NTM group included 384 patients who had 0 to ≤10 days of telemonitoring during follow-up.Primary and secondary outcome measures The primary outcome was the rate of NIV dropouts at 1 year (ie, treatment discontinuation, excluding deaths). Secondary outcomes included therapy compliance and leaks.Results 82 patients died during follow-up. Significantly fewer patients in the TM vs NTM group had dropped out of NIV therapy at 1 year (13% vs 34%; p4 hours/day and control of leaks.Conclusions In patients starting home NIV, TM with home care provider first-line support was associated with a lower therapy dropout rate at 1 year, and better compliance and leak control, compared with standard follow-up.

Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.