bluuebunny/crossref_metadata_2025_split huggingface dataset:
The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner
Authors: Stock Amanda J. , Gonzalez-Paredes Pierina , Previato de Almeida Luciana , Kosanke Stanley D. , Chetlur Srinivaas , Budde Hannah , Wakenight Paul , Zwingman Theresa A. , Rosen Aaron B. , Allenspach Eric , Millen Kathleen J. , Buckner Jane H. , Rawlings David J. , Gorman Jacquelyn A. 
Published: January 2024

ABSTRACTType 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1A946T) and confers an increased risk for several autoimmune diseases, including T1D. We hypothesized that theIFIH1A946Trisk variant, (IFIH1R) would promote T1D pathogenesis by stimulating type I interferon (IFN I) signaling leading to immune cell alterations. To test this, we developedIfih1Rknock-in mice on the non-obese diabetic (NOD) mouse background, a spontaneous T1D model. Our results revealed a modest increase in diabetes incidence and insulitis inIfih1Rcompared to non-riskIfih1(Ifih1NR)mice and a significant acceleration of diabetes onset inIfih1Rfemales.Ifih1Rmice exhibited a significantly enhanced interferon stimulated gene (ISG) signature compared toIfih1NR, indicative of increased IFN I signaling.Ifih1Rmice exhibited an increased frequency of plasma cells as well as tissue-dependent changes in the frequency and activation of CD8+T cells. Our results indicate thatIFIH1Rmay contribute to T1D pathogenesis by altering the frequency and activation of immune cells. These findings advance our knowledge on the connection between the rs1990760 variant and T1D. Further, these data are the first to demonstrate effects ofIfih1Rin NOD mice, which will be important to consider for the development of therapeutics for T1D.
Task-related modulation of event-related potentials does not reflect changes to sensory representations
Authors: Rideaux Reuben 
Published: January 2024

ABSTRACTAttention supports efficient perception by increasing the neural signals of targets while supressing those of distractors. Decades of work studying the event-related potentials of electroencephalography (EEG) recordings have established our understanding of attention in the human brain, but many aspects of this phenomenon remain unknown. Several recent studies suggest that multivariate analyses may provide new insights into how attention shapes the neural representations of stimuli; however, it is unclear whether the increased multivariate decoding accuracy associated with task relevance represents a change in the stimulus representation or an additional cognitive process. To understand what the change in multivariate information that is associated with task relevance reflects, here we used inverted encoding to characterize how task relevance shapes the neural representation of space and colour. For both spatial and feature-based tasks, we found that the change in the EEG recordings associated with task relevance is not related to the stimulus representation. Rather, our findings indicate that this phenomenon reflects an additional cognitive process, such as target recognition.
Protected area establishment in Southern and Eastern Africa: Consequences for management today
Authors: Schroder Bradley , Van Langevelde Frank , Schroder Nicola-Anne Hawkins , Prins Herbert H. T. 
Published: January 2024

AbstractTo understand the complexities of managing protected areas, it is important to understand the causes for their established. We summarized the motives for establishing protected areas in Southern and Eastern Africa, and the possible consequences for management of these areas today. We scrutinised documents for 48 randomly selected protected areas and investigated, (1) when and why each of the protected areas was established? (2) what the management implications were of the reasons for incorporation for these areas? and (3) how/if the original management still impacts conservation in these areas today? First, we learnt that the establishment of protected areas occurred in three periods, namely,Period 1when area protection was started to protect wild animals from decimation;Period 2during which areas considered marginal for agriculture, prone to disease or sickness and considered uninhabitable for humans were set aside; andPeriod 3when areas were proclaimed protected because of ecological or cultural importance. Second, we showed that the establishment of protected areas has ramifications for management of these areas today, which for Period 1 were remote logistics and tourism, anti-poaching difficulties, large size logistics and human wildlife conflict. Period 2 has consequences for community-land issues and intensive management, with Period 3 having intensive management to meet the objectives of these parks. Our insights have consequences for management of protected areas today, with Period 1 protected areas generally being managed on a laissez-faire approach and Period 2 and 3 protected areas being managed on a more intensive management basis.
The chromosome-level genome of the ctenophoreMnemiopsis leidyiA. Agassiz, 1865 reveals a unique immune gene repertoire
Authors: Koutsouveli Vasiliki , Torres-Oliva Montserrat , Bayer Till , Fuß Janina , Grossschmidt Nora , Marulanda-Gomez Angela M. , Gill Diana , Schmitz Ruth A. , Pita Lucía , Reusch Thorsten B. H. 
Published: January 2024

AbstractCtenophora are basal marine metazoans, the sister group of all other animals.Mnemiopsis leidyiis one of the most successful invasive species worldwide with intense ecological and evolutionary research interest. Here, we generated a chromosome-level genome assembly ofM. leidyiwith a focus on its immune gene repertoire. The genome was 247.97 Mb, with N50 16.84 Mb, and 84.7% completeness. Its karyotype was 13 chromosomes. In this genome and that of two other ctenophores,Bolinopsis micropteraandHormiphora californensis, we detected a high number of protein domains related to potential immune receptors. Among those, proteins containing Toll/interleukin-1(TIR2) domain, NACHT domain, Scavenger Receptor Cystein-Rich (SRCR) domain, or C-type Lectin domain (CTLD) were abundant and presented unique domain architectures inM. leidyi. M. leidyiseems to lackbona fideToll like Receptors, but it does possess a repertoire of 15 TIR2-domain containing genes. Besides, we detected abona fideNOD-like receptor and 38 NACHT-domain containing genes. In order to verify the function of those domain containing genes, we exposedM. leidyito the pathogenVibrio coralliilyticus. Among the differentially expressed genes, we identified potential immune receptors, including four TIR2-domain containing genes, all of which were upregulated in response to pathogen exposure. To conclude, many common immune receptor domains, highly conserved across metazoans, are already present in Ctenophora. These domains have large expansions and unique architectures inM. leidyi, findings consistent with the basal evolutionary position of this group, but still might have conserved functions in immunity and host-microbe interaction.
A Comprehensive Evaluation of Large Language Models in Mining Gene Interactions and Pathway Knowledge
Authors: Azam Muhammad , Chen Yibo , Arowolo Micheal Olaolu , Liu Haowang , Popescu Mihail , Xu Dong 
Published: January 2024

AbstractBackgroundUnderstanding complex biological pathways, including gene-gene interactions and gene regulatory networks, is critical for exploring disease mechanisms and drug development. Manual literature curation of biological pathways is useful but cannot keep up with the exponential growth of the literature. Large-scale language models (LLMs), notable for their vast parameter sizes and comprehensive training on extensive text corpora, have great potential in automated text mining of biological pathways.MethodThis study assesses the effectiveness of 21 LLMs, including both API-based models and open-source models. The evaluation focused on two key aspects: gene regulatory relations (specifically, ‘activation’, ‘inhibition’, and ‘phosphorylation’) and KEGG pathway component recognition. The performance of these models was analyzed using statistical metrics such as precision, recall, F1 scores, and the Jaccard similarity index.ResultsOur results indicated a significant disparity in model performance. Among the API-based models, ChatGPT-4 and Claude-Pro showed superior performance, with an F1 score of 0.4448 and 0.4386 for the gene regulatory relation prediction, and a Jaccard similarity index of 0.2778 and 0.2657 for the KEGG pathway prediction, respectively. Open-source models lagged their API-based counterparts, where Falcon-180b-chat and llama1-7b led with the highest performance in gene regulatory relations (F1 of 0.2787 and 0.1923, respectively) and KEGG pathway recognition (Jaccard similarity index of 0.2237 and 0. 2207, respectively).ConclusionLLMs are valuable in biomedical research, especially in gene network analysis and pathway mapping. However, their effectiveness varies, necessitating careful model selection. This work also provided a case study and insight into using LLMs as knowledge graphs.
Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase
Authors: Lama-Diaz Tomas , Blanco Miguel G. 
Published: January 2024

AbstractIn budding yeast, the integrity of both the nuclear and mitochondrial genomes relies on dual-targeted isoforms of the conserved Pif1 helicase, generated by alternative translation initiation (ATI) ofPIF1mRNA from two consecutive AUG codons flanking a mitochondrial targeting signal. Here, we demonstrate that ribosomal leaky scanning is the specific ATI mechanism that produces not only these, but also novel, previously uncharacterized Pif1 isoforms. Both in-frame, downstream AUGs as well as near-cognate start codons contribute to the generation of these alternative isoforms. This has crucial implications for the rational design of genuine separation-of-function alleles and provides an explanation for the suboptimal behaviour of the widely employed mitochondrial- (pif1-m1) and nuclear-deficient (pif1-m2) alleles, with mutations in the first or second AUG codon, respectively. We have taken advantage of this refined model to develop improved versions of these alleles, which will serve as valuable tools to elucidate novel functions of this helicase and to disambiguate previously described genetic interactions ofPIF1in the context of nuclear and mitochondrial genome stability.
Linear-regression-based algorithms can succeed at identifying microbial functional groups despite the nonlinearity of ecological function
Authors: Zhao Yuanchen , Cordero Otto X. , Tikhonov Mikhail 
Published: January 2024

AbstractMicrobial communities play key roles across diverse environments. Predicting their function and dynamics is a key goal of microbial ecology, but detailed microscopic descriptions of these systems can be prohibitively complex. One approach to deal with this complexity is to resort to coarser representations. Several approaches have sought to identify useful groupings of microbial species in a data-driven way. Of these, recent work has claimed some empirical success atde novodiscovery of coarse representations predictive of a given function using methods as simple as a linear regression, against multiple groups of species or even a single such group (the EQO approach of Shanet al. [25]). This success seems puzzling, since modeling community function as a linear combination of contributions of individual species appears simplistic. However, the task of identifying a predictive coarsening of an ecosystem is distinct from the task of predicting the function well, and it is conceivable that the former could be accomplished by a simpler methodology than the latter. Here, we use the resource competition framework to design a model where the “correct” grouping to be discovered is well-defined, and use synthetic data to evaluate and compare three regression-based methods, namely, two proposed previously and one we introduce. We find that regression-based methods can recover the groupings even when the function is manifestly nonlinear; that multi-group methods offer an advantage over a single-group EQO; and crucially, that simpler (linear) methods can outperform more complex ones.Author summaryNatural microbial communities are highly complex, making predictive modeling difficult. One appealing approach is to make their description less detailed, rendering modeling more tractable while hopefully still retaining some predictive power. The Tree of Life naturally provides one possible method for building coarser descriptions (instead of thousands of strains, we could think about hundreds of species; or dozens of families). However, it is known that useful descriptions need not be taxonomically coherent, as illustrated, for example, by the so-called functional guilds. This prompted the development of computational methods seeking to propose candidate groupings in a data-driven manner. In this computational study, we examine one class of such methods, recently proposed in the microbial context. Quantitatively testing their performance can be difficult, as the answer they “should” recover is often unknown. Here, we overcome this difficulty by testing these methods on synthetic data from a model where the ground truth is known by construction. Curiously, we demonstrate that simpler approaches, rather than suffering from this simplicity, can in fact be more robust.
Impact of maternal obesogenic diet on maternal and offspring microbiome development
Authors: Hasebe Kyoko , Kendig Michael D , Kaakoush Nadeem O , Tajaddini Aynaz , Westbrook R Frederick , Morris Margaret J 
Published: January 2024

AbstractPregnancy can alter gut microbiota composition, but how an obesogenic diet impacts maternal gut microbiota, and the extent to which this influences offspring microbiome can be obscured by confounding factors. This study examined changes in gut microbiota composition across pre-pregnancy, gestation and lactation in rat dams fed either a high-fat, high-sugar Cafeteria (Caf) diet or Chow. Microbiome development was assessed in their offspring weaned onto chow. Caf diet consumption during pregnancy increased weight gain and adiposity, and compromised subsequent maternal nursing behaviour. α- and β diversity measures in Caf-fed dams showed a different trajectory across the progression of pregnancy, with no change inBacteroidetesandFirmicutesabundance compared with Chow dams. Offspring born to Caf dams exhibited greater adiposity and plasma leptin at weaning and 14 weeks of age than those born to Chow dams. Maternal Caf diet induced clear differences in β diversity in weanlings but not α diversity. SourceTracker analysis revealed similarities in the gut microbiota of Chow weanlings and maternal gut microbiota in lactation, whereas the microbiota of Caf weanlings was similar to the maternal gut microbiota during gestation. Maternal Caf diet exerted only marginal effects on gut microbiota composition in 14-week-old offspring.
Narcissus reflected: gray and white matter features joint contribution to the default mode network in predicting narcissistic personality traits
Authors: Jornkokgoud Khanitin , Baggio Teresa , Bakiaj Richard , Wongupparaj Peera , Job Remo , Grecucci Alessandro 
Published: January 2024

AbstractDespite the clinical significance of narcissistic personality, its neural bases have not been clear yet, primarily due to methodological limitations of the previous studies, such as the low sample size, the use of univariate techniques and the focus on only one brain modality. In this study, we employed for the first time a combination of unsupervised and supervised machine learning methods, to identify the joint contributions of gray (GM) and white matter (WM) to narcissistic personality traits (NPT). After preprocessing, the brain scans of 135 participants were decomposed into eight independent networks of covarying GM and WM via Parallel ICA. Subsequently, stepwise regression and Random Forest were used to predict NPT. We hypothesize that a fronto-temporo parietal network mainly related to the Default Mode Network, may be involved in NPT and white matter regions related to these regions. Results demonstrated a distributed network that included GM alterations in fronto-temporal regions, the insula, and the cingulate cortex, along with WM alterations in cerebellar and thalamic regions. To assess the specificity of our findings, we also examined whether the brain network predicting narcissism could predict other personality traits (i.e., Histrionic, Paranoid, and Avoidant personalities). Notably, this network did not predict these personality traits. Additionally, a supervised machine learning model (Random Forest) was used to extract a predictive model to generalize to new cases. Results confirmed that the same network could predict new cases. These findings hold promise for advancing our understanding of personality traits and potentially uncovering brain biomarkers associated with narcissism.
Physical activity and fiber intake beneficial for muscle mass and strength preservation during aging: A Comprehensive Cross-Sectional Study in the UK Biobank cohort
Authors: Morwani-Mangnani Jordi , Rodriguez-Girondo Mar , Singh-Povel Cecile , Verlaan Sjors , Beekman Marian , Slagboom P. Eline 
Published: January 2024

ABSTRACTBackgroundAging triggers intricate physiological changes, particularly in muscle mass and strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, exercise, and sleep independently and differentially impact on muscle mass and strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health.MethodsThe cross-sectional analysis of the UK Biobank involved 45,984 individuals aged 40-70. Multiple linear regression explored determinants of whole-body fat-free mass and handgrip strength, considering traditional, socio-demographics, medication use and smoking as covariates, with gender and age (younger and older than 55 years) stratifications.ResultsHigher physical activity and fiber intake beneficially affect both muscle mass and strength, especially above 55 years. Other lifestyle factors influence the two muscle parameters differently. Key determinants influencing muscle strength included higher protein intake, lower water intake, higher alcohol intake, and extended sleep duration whereas mainly higher water intake contributes to higher muscle mass.ConclusionsPhysical activity and fiber intake associate with increased muscle strength and mass which may connect gut and muscle health. Given the observed complexity of muscle health in the age and gender strata, further longitudinal research is needed to provide personalized lifestyle recommendations.
A head-mounted Tilted Reality Device for the treatment of pusher syndrome: A usability study
Authors: Wöhrstein Sofia , Bressler Michael , Röhrig Lisa , Prahm Cosima , Karnath Hans-Otto 
Published: January 2024

AbstractPusher syndrome is a disorder of postural control after stroke. Patients show a mismatch in their perception of (almost preserved) visual and (pathologically tilted) postural verticality. In order to reduce this mismatch, we developed a novel head-mounted ‘Tilted Reality Device (TRD)’. It presents patients visual footage of their actual surroundings but tilted to one side rather than upright. We investigated its usability and possible limitations in its use for the treatment of pusher patients in two samples of healthy participants with an average age of 26.4 years and 63.9 years respectively. Individuals from both age groups showed similar levels of tolerance to prolonged exposure to the tilted visual environment for an average of 40.4 minutes while walking around in the hospital. The TRD was found to be comfortable and not frustrating whilst wearing, but somewhat challenging in terms of technical handling, particularly for older participants. At the end of the maximally tolerated exposure time participants of both groups experienced some feelings of discomfort, like dizziness or increased stomach awareness, which disappeared rapidly after terminating TRD exposure. Our TRD appears to be a practical device especially for an older population, like pusher patients. While users must be aware of the possibility of side effects, these should be balanced against the benefits of future use for rehabilitation purposes.
Sex-Based Utilization of Guideline Recommended Statin Therapy and Cardiovascular Disease Outcomes: A Primary Prevention Healthcare Network Registry
Authors: Koczo Agnes , Brickshawana Adipong , Zhu Jianhui , Thoma Floyd , Countouris Malamo , Berlacher Kathryn , Gulati Martha , Michos Erin D , Reis Steven , Mulukutla Suresh , Saeed Anum 
Published: January 2024

AbstractBackgroundIn the US, women have similar cardiovascular death rates than men. Less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes.MethodsStatin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013-2019. Guideline-directed statin intensity (GDSI) at index and follow-up visits were compared among sexes across ASCVD risk groups, defined by pooled-cohort equation. Cox regression hazard ratios (HR) [95% CI] were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied.ResultsAmong 282,298 patients, (mean age ∼ 50 years) 17.1% women and 19.5% men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-ups was lower compared to high-risk men (2-years: 27.7 vs 32.0%, and 5-years: 47.2 vs 55.2%, p<0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA amongst both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) versus men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004).ConclusionIn a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to be initiated on GDSI compared with high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.