bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting bipolar disorder incidence in young adults using gradient boosting: a 5-year follow-up study
Authors: Montezano Bruno Braga , Gnielka Vanessa , Shintani Augusto Ossamu , de Aguiar Kyara Rodrigues , Roza Thiago Henrique , de Azevedo Cardoso Taiane , de Mattos Souza Luciano Dias , Moreira Fernanda Pedrotti , da Silva Ricardo Azevedo , Mondin Thaíse Campos , Jansen Karen , Passos Ives Cavalcante 
Published: April 2023

AbstractThis study aimed to develop a classification model predicting incident bipolar disorder (BD) cases in young adults within a 5-year interval, using sociodemographic and clinical features from a large cohort study. We analyzed 1,091 individuals without BD, aged 18 to 24 years at baseline, and used the XGBoost algorithm with feature selection and oversampling methods. Forty-nine individuals (4.49%) received a BD diagnosis five years later. The best model had an acceptable performance (test AUC: 0.786, 95% CI: 0.686, 0.887) and included ten features: feeling of worthlessness, sadness, current depressive episode, selfreported stress, self-confidence, lifetime cocaine use, socioeconomic status, sex frequency, romantic relationship, and tachylalia. We performed a permutation test with 10,000 permutations that showed the AUC from the built model is significantly better than random classifiers. The results provide insights into BD as a latent phenomenon, as depression is its typical initial manifestation. Future studies could monitor subjects during other developmental stages and investigate risk populations to improve BD characterization. Furthermore, the usage of digital health data, biological, and neuropsychological information and also neuroimaging can help in the rise of new predictive models.
Is there a bilingual advantage in auditory attention among children? A systematic review and meta-analysis of standardized auditory attention tests
Authors: Bao Wenfu , Alain Claude , Thaut Michael , Molnar Monika 
Published: April 2023

AbstractA wealth of research has investigated the effects of bilingualism on cognition, especially on executive function. Developmental studies reveal different cognitive profiles between monolinguals and bilinguals in (audio-)visual attention tasks, which might stem from their attention allocation differences. Yet, whether such distinction exists in the auditory domain alone is unknown. In this study, we compared differences in auditory attention, measured by standardized tests, between monolingual and bilingual children. A comprehensive literature search was conducted in three electronic databases: OVID Medline, OVID PsycInfo, and EBSCO CINAHL. Twenty studies using standardized tests to assess auditory attention in monolingual and bilingual participants aged less than 18 years were identified. We assessed the quality of these studies using a scoring tool for evaluating primary research. For statistical analysis, we pooled the effect size in a random-effects meta-analytic model, where between-study heterogeneity was quantified using theI2statistic. No substantial publication bias was observed based on the funnel plot. Further, meta-regression modelling suggests that test measure (accuracy vs. response times) significantly affected the studies’ effect sizes whereas other factors (e.g., participant age, stimulus type) did not. Specifically, studies reporting accuracy observed marginally greater accuracy in bilinguals (g= 0.10), whereas those reporting response times indicated faster latency in monolinguals (g= -0.34). There was little difference between monolingual and bilingual children’s performance on standardized auditory attention tests. We also found that studies tend to include a wide variety of bilingual children but report limited language background information of the participants. This, unfortunately, limits the potential theoretical contributions of the reviewed studies. Recommendations to improve the quality of future research are discussed.
A nationwide multistate analysis estimating the rates and risks of transferring critically ill COVID-19 patients during the Delta and Omicron waves in Germany
Authors: Lottes Matthäus , Grodd Marlon , Grabenhenrich Linus , Wolkewitz Martin 
Published: April 2023

AbstractBackgroundThe spread of several SARS-CoV-2 variants of concern (VOC) led to increasing numbers of patients with coronavirus disease 2019 (COVID-19) in German intensive care units (ICU), resulting in capacity shortages and even transfers of COVID-19 ICU patients between federal states in late 2021. Comprehensive evidence on the impact of predominant VOC, in this case Delta and Omicron, on inter-hospital transfers of COVID-19 ICU patients remains scarce.MethodsA retrospective cohort study was conducted from July 01, 2021 until May 31, 2022 using nationwide reimbursement inpatient count data of COVID-19 ICU patients and weekly sequence data of VOC in Germany. A multivariable Poisson regression analysis was performed to estimate incidence rates and incidence rate ratios (IRR) for competing events of transfer, discharge and death, adjusted for VOC infection, age group and sex. For corresponding risk estimation, a multistate model for the clinical trajectory in ICU was applied.ResultsOmicron versus Delta infection yielded estimated adjusted IRR of 1.23 (95% CI, 1.16 – 1.30) for transfer, 2.27 (95% CI, 2.20 – 2.34), for discharge and 0.98 (95% CI, 0.94 – 1.02) for death. For death in ICU, estimated adjusted IRR increased progressively with age up to 4.09 (95% CI, 3.74 – 4.47) for those 90 years and older. COVID-19 ICU patients with Omicron infection were at comparatively higher estimated risk of discharge, whereas the estimated risk of transfer and death were higher for those with Delta infection.ConclusionsInter-hospital transfers and discharges occurred more frequently in COVID-19 ICU patients with Omicron infection than in those with Delta infection, who in turn had a higher estimated risk of death. Age emerges as a relevant determinant for fatal clinical trajectories in COVID-19 ICU patients and imposes close therapeutic care.
The Impact Of Alcohol Minimum Unit Pricing On People with experience of Homelessness: Qualitative Study
Authors: Emslie Carol , Dimova Elena , O’Brien Rosaleen , Whiteford Martin , Johnsen Sarah , Rush Robert , Smith Iain D. , Stockwell Tim , Whittaker Anne , Elliott Lawrie 
Published: April 2023

ABSTRACTBACKGROUNDAlcohol Minimum Unit Pricing (MUP) was introduced in Scotland in May 2018. Existing evidence suggests MUP can reduce alcohol consumption in the general population, but there is little research about its impact on vulnerable groups. This qualitative study aimed to explore experiences of MUP among people with experience of homelessness.METHODSWe conducted qualitative semi-structured interviews with a purposive sample of 46 people with current or recent experience of homelessness who were current drinkers when MUP was introduced. Participants (30 men and 16 women) were aged 21 to 73 years. Interviews focused on views and experiences of MUP. Data were analysed using thematic analysis.RESULTSPeople with experience of homelessness were aware of MUP but it was accorded low priority in their hierarchy of concerns. Reported impacts varied. Some participants reduced their drinking, or moved away from drinking strong white cider in line with policy intentions. Others were unaffected because the cost of their preferred drink (usually wine, vodka or beer) did not change substantially. A minority reported increased involvement in begging. Wider personal, relational and social factors also played an important role in participant responses to MUP.CONCLUSIONOur findings suggest that MUP worked as intended for some people with experience of homelessness, while a minority reported negative consequences. Our findings highlight the importance of considering the impact of population level health policies on marginalised groups. Policymakers in Scotland, and elsewhere, need to consider wider contextual factors that affect responses to MUP in people with experience of homelessness. It is important to invest further in secure housing and appropriate support services for people with experience of homelessness who consume alcohol, and implement and evaluate harm reduction initiatives such as managed alcohol programmes.
Toxoplasma gondiiinfection alters the recognition response of dendritic cells to stiffness substrate
Authors: Sun ZhePeng , Liu Jing , Zhu ZiFu , Ying Zhu , Zhou ZiHui , Liu Qun 
Published: April 2023

AbstractToxoplasma gondii(T.gondii) hijacks host immune cells as ‘Trojan Horse’, and the infected cells accelerated the parasites dissemination. During acute infection,T.gondiispecificity crosses the blood-brain-barrier to enter the brain. This selective mode of parasite transmission may be associated with the directed migration of infected immune cells. Immune cells follow various environmental cues for directional migration. However, the effect ofT.gondiiinfection on the recognition of mechanical cues by immune cells remains unknown. Here, we examined the adhesion and migration ofT.gondii-infected dendritic cells (DCs) on high and low stiffness substrates. We found thatT.gondiiinfection alters the durotaxis migration of DCs. Infected DC exhibited stronger adhesion and lower migration on low stiffness substrates. In contrast to uninfected DCs, infected DCs migrated towards the low stiffness environment. TgWIP and TgROP17 co-regulate the F-actin structure of DCs and are involved in the formation of abnormal F-actin filaments. Rearrangement of the F-actin structure resulting fromT.gondiiinfection regulates DCs’ abnormal recognition response to the mechanical cues. Recognition of DCs to the mechanical signals is independent of β2- integrin expression. Meanwhile, challenging DCs withT.gondiiincreased the phosphorylation of focal adhesion kinase (FAK). Treatment with a FAK inhibitor (VS- 6063) influences the recognition response of infected DCs. FAK inhibition in adoptively transferred infected DCs effectively prevents the dissemination ofT.gondiito the brain. The data reveal thatT.gondiiinfection inversely affects the durotaxis of DCs by altering the phosphorylation level of FAK and remodeling of F-actin structure.T.gondiiutilizes the change in DCs’ durotaxis migration to accelerate the parasites crossing the blood-brain-barrier.Author SummaryImmune cells travel through blood vessels and lymph vessels to various tissues, and respond to different types of environmental cues. Cells sense the cues and transmit these information to the cytoskeletal which induce directed cell migration towards or away from these signals.T.gondiiinfection remodeling the cytoskeletal of DCs which may cause abnormalities in these cues transduction. We found thatT.gondiiinfection induces the formation of abnormal F-actin filaments in DCs, TgWIP and TgROP17 co-regulate the DCs’ F-actin structure.T.gondiiinfection increased the phosphorylation of FAK in DCs and has no effect with DCs surface β2-integrin expression. These reasons lead to alter the original durotaxis migration of DCs, and makes infected-DCs tend to stay in the low stiffness environment. Meanwhile, the recognition response of infected DC to mechanical signal determines the parasite rapid crossing the blood-brain-barrier.
Genetic impacts on DNA methylation help elucidate regulatory genomic processes
Authors: Villicaña Sergio , Castillo-Fernandez Juan , Hannon Eilis , Christiansen Colette , Tsai Pei-Chien , Maddock Jane , Kuh Diana , Suderman Matthew , Power Christine , Relton Caroline , Ploubidis George , Wong Andrew , Hardy Rebecca , Goodman Alissa , Ong Ken K. , Bell Jordana T. 
Published: April 2023

AbstractPinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2,358 blood samples from three UK cohorts, with replication. Methylation levels at 34.2% of CpGs were affected by SNPs, and 98% of effects werecis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both meQTL SNPs and CpGs with meQTLs were overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identified 1,520 co-localisations across 1,325 unique CpGs and 34 phenotypes, including in disease-relevant genes, suchICOSLG(inflammatory bowel disease), andUSP1andDOCK7(total cholesterol levels). Enrichment analysis of meQTLs and integration with expression QTLs gave insights into mechanisms underlyingcis-meQTLs, for example through disruption of transcription factor binding sites for CTCF and SMC3, andtrans-meQTLs, for example through regulating the expression ofACDandSENP7which can modulate DNA methylation at distal sites. Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. A results database and viewer are available online.
Dynamic molecular mechanism of the nuclear pore complex permeability barrier
Authors: Kozai Toshiya , Fernandez-Martinez Javier , van Eeuwen Trevor , Gallardo Paola , Kapinos Larisa E. , Mazur Adam , Zhang Wenzhu , Tempkin Jeremy , Panatala Radhakrishnan , Delgado-Izquierdo Maria , Raveh Barak , Sali Andrej , Chait Brian T. , Veenhoff Liesbeth M. , Rout Michael P. , Lim Roderick Y. H. 
Published: April 2023

AbstractNuclear pore complexes (NPCs) mediate nucleocytoplasmic transport of specific macromolecules while impeding the exchange of unsolicited material. However, key aspects of this gating mechanism remain controversial. To address this issue, we determined the nanoscopic behavior of the permeability barrier directly within yeastS. cerevisiaeNPCs at transport-relevant timescales. We show that the large intrinsically disordered domains of phenylalanine-glycine repeat nucleoporins (FG Nups) exhibit highly dynamic fluctuations to create transient voids in the permeability barrier that continuously shape-shift and reseal, resembling a radial polymer brush. Together with cargo-carrying transport factors the FG domains form a feature called the central plug, which is also highly dynamic. Remarkably, NPC mutants with longer FG domains show interweaving meshwork-like behavior that attenuates nucleocytoplasmic transportin vivo. Importantly, thebona fidenanoscale NPC behaviors and morphologies are not recapitulated byin vitroFG domain hydrogels. NPCs also exclude self-assembling FG domain condensatesin vivo, thereby indicating that the permeability barrier is not generated by a self-assembling phase condensate, but rather is largely a polymer brush, organized by the NPC scaffold, whose dynamic gating selectivity is strongly enhanced by the presence of transport factors.
Heat-inactivated mycobacteria activate the Toll-like receptor 2 and 4 pathways in the zebrafish model of tuberculosis
Authors: Ferreras-Colino Elisa , Contreras Marinela , Risalde María A. , Sevilla Iker A. , Delgado Encarnación , Domínguez Lucas , Gortazar Christian , de la Fuente Jose 
Published: April 2023

AbstractBased on previous evidence demonstrating the efficacy of inactivated mycobacteria for the control of fish mycobacteriosis, we explored the protective efficacy of two inactivatedMycobacterium bovisadministered via parenteral and mucosal routes againstMycobacterium marinuminfection mimicking natural conditions in the zebrafish model of tuberculosis. Although we did not observe a clear effect of any of the immunostimulants on mycobacterial burden, the results showed a significant increase in TLR2 and TLR4 gene expression levels in fishes parenterally immunized with inactivated Bacillus Calmette-Guérin (BCG). Our findings demonstrated that the TLR2 and the TLR4 signaling pathways are involved in the immune response elicited by inactivated mycobacteria in the zebrafish model of tuberculosis and support the use of inactivated mycobacteria in vaccine formulations for the control of mycobacteriosis.
Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing
Authors: Cui Leilei , Yang Bin , Xiao Shijun , Gao Jun , Baud Amelie , Graham Delyth , McBride Martin , Dominiczak Anna , Schafer Sebastian , Aumatell Regina Lopez , Mont Carme , Teruel Albert Fernandez , Hübner Norbert , Flint Jonathan , Mott Richard , Huang Lusheng 
Published: April 2023

ABSTRACTBackgroundDominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena played a major role in quantitative genetics. However, today most genome-wide association studies (GWAS) assume alleles act additively.MethodsWe systematically investigated both dominance – here representing any non-additive effect - and additivity across 574 physiological and gene expression traits in three mammalian models: a Pig F2 Intercross, a Rat Heterogeneous Stock and a Mouse Heterogeneous Stock.ResultsIn all species, and across all physiological traits, dominance accounts for about one quarter of the heritable variance. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable assuming additivity, we identified 154, 64 and 62 novel dominance QTLs in pigs, rats and mice respectively, that were undetectable as additive QTLs. Similarly, even though most cis-acting eQTLs are additive, we observed a large fraction of dominance variance in gene expression, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, in HS rat transcriptomes, thousands of eQTLs associate with alternate transcripts and exhibit complex additive and dominant architectures, suggesting a mechanism for dominance.ConclusionsAlthough heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.
Avoiding false discoveries: Revisiting an Alzheimer’s disease snRNA-Seq dataset
Authors: Murphy Alan E , Fancy Nurun Nahar , Skene Nathan G 
Published: April 2023

AbstractMathyset al., conducted the first single-nucleus RNA-Seq study (snRNA-Seq) of Alzheimer’s disease (AD)1. The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with varying degrees of AD pathology. With bulk RNA-Seq, changes in gene expression across cell types can be lost, potentially masking the differentially expressed genes (DEGs) across different cell types. Through the use of single-cell techniques, the authors benefitted from increased resolution with the potential to uncover cell type-specific DEGs in AD for the first time2. However, there were limitations in both their data processing and quality control and their differential expression analysis. Here, we correct these issues and use best-practice approaches to snRNA-Seq differential expression, resulting 549 times fewer differentially expressed genes at a false discovery rate (FDR) of 0.05.
Development and Validation of a Novel Instrument to Capture Companion Dog Mortality Data: The Dog Aging Project End of Life Survey
Authors: McNulty Kellyn E. , Creevy Kate E. , Fitzpatrick Annette , Wilkins Vanessa , Barnett Brian G. ,   DAP Consortium, Ruple Audrey 
Published: April 2023

AbstractObjectiveThe researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs.SampleBereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n=42) and/or completed the entire survey between January 20 and March 24, 2021 (n=646).ProceduresThe EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post-hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs’ death.ResultsThe EOLS was well-received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the three validation themes: cause of death (kappa = 0.73; 95% CI [0.5-0.95]), perimortem quality of life (kappa = 0.49; 95% CI [0.26-0.73]), and reason for euthanasia (kappa = 0.3; 95% CI [0.08-0.52]) and had no need for any substantial content alterations based on free-text analysis.Clinical RelevanceThe EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians’ ability to care for the aging dog population by illuminating their understanding of companion dogs’ end-of-life experiences.
Feature Engineering for an Efficient Motor Related EcoG BCI System
Authors: Jain Ritwik , Jaiman Prakhar , Baths Veeky 
Published: April 2023

AbstractInvasive Brain Computer Interface (BCI) systems through Electrocorticographic (ECoG) signals require efficient recognition of spatiotemporal patterns from a multi-electrodes sensor array. Such signals are excellent candidates for automated pattern recognition through machine learning algorithms. The importance of these patterns can be highlighted through feature extraction techniques. However, the signal variability due to non-stationarity is ignored while extracting features, and which features to use can be challenging to figure out by visual inspection. In this study, we introduce the signal split parameter to account for the variability of the signal and increase the accuracy of the machine learning classifier. We use genetic selection, which allows the selection of the optimal combination of features from a pool of 8 different feature sets. Genetic selection of features increases accuracy and reduces the BCI’s prediction time. Along with Genetic selection, we also use a reduced signal length, which leads to a higher Information Transfer Rate. Thus this approach enables the design of a fast and accurate motorrelated EcoG BCI system.