bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring archaeogenetic studies of dental calculus to shed light on past human migrations in Oceania
Authors: Velsko Irina M. , Fagernäs Zandra , Tromp Monica , Bedford Stuart , Buckley Hallie R. , Clark Geoffrey , Dudgeon John , Flexner James , Leal-Tamarii Anatauarii , Lewis Cecil M. , Matisoo-Smith Elizabeth , Nägele Kathrin , Ozga Andrew T. , Rohrlach Adam B. , Posth Cosimo , Shing Richard , Spriggs Matthew , Willie Edson , Valentin Frédérique , Warinner Christina 
Published: October 2023

AbstractThe Pacific islands have experienced multiple waves of human migrations, providing a case study for exploring the potential of using the microbiome to study human migration. We performed a metagenomic study of archaeological dental calculus from 103 ancient individuals, originating from 12 Pacific islands and spanning a time range of ∼3000 years. Oral microbiome DNA preservation in calculus is far higher than that of human DNA in archaeological bone from the Pacific, and comparable to that seen in calculus from temperate regions. Variation in the microbial community composition was minimally driven by time period and geography within the Pacific, while comparison with samples from Europe, Africa, and Asia reveal the microbial communities of Pacific calculus samples to be distinctive. Phylogenies of individual bacterial species in Pacific calculus reflect geography. Archaeological dental calculus shows potential to yield information about past human migrations, complementing studies of the human genome.
Jet Lag Does Not Impact Football Performance: Using Randomization Inference to Handle Complexity
Authors: Tenan Matthew S. , Rezai Ali R. , Vigotsky Andrew D. 
Published: October 2023

AbstractIntroductionIt is commonly accepted that traveling across time zones affects sport performance (i.e., via jet lag). This belief is based on poor quality evidence for team sports and simplistic analyses, such ast-tests and linear regression, to explore complex phenomena. For instance, Roy & Forest used such analyses to examine win percentages for the NFL, NBA, and NHL, concluding that East Coast teams were disadvantaged. Similarly, Smith et al. primarily usedt-tests to show that West Coast NFL teams were more likely than East Coast teams to beat the Vegas spread in evening games (non-coastal teams were omitted). Neither analysis considered time zone change or game time as continuous constructs nor did they account for important contextual information. We used modern causal inference methods and a decade of collegiate football games to determine if jet lag and kickoff time have any causal effect on beating the Vegas spread. This required fitting nonlinear splines for both data re-weighting and analysis; however, using weights in a generalized additive model (GAM) presents challenges for standard frequentist inferences. Thus, non-parametric simulations were developed to obtain valid causal inferences via randomization inference (RI).MethodsPro Football Focus data from college football seasons 2013–2022 were paired with time zone data from Google Maps, weather data from gridMET, and Vegas spread data fromcollegefootballdata.com. GAM-based propensity scores were calculated from turf type, precipitation, humidity, temperature, and wind speed. These propensity scores orthogonalized the variables relationship to the treatments (i.e., game time and hours gained due to time zone change), consistent with the Potential Outcomes framework. The propensity scores were used to weight the observations in a GAM logistic regression, which modeled beating the Vegas spread as a function of a splined effect modification for game time and hours gained in travel. Since valid standard errors cannot be calculated from GAMs with weights, we used RI to compare the effect modification to a null model. We simulated 5,000 datasets of random treatments under the positivity assumption. Each RI dataset was analyzed with the same GAM used for the observed data to obtain a distribution of noiseF-statistics. The real dataF-statistic was contrasted to the RI distribution for inferences.ResultsThe real data were compatible with the null hypothesis of no effect for hours lost/gained in travel and game time (P= 0.142).ConclusionWe need to rigorously interrogate assumptions regarding what affects performance in team sports. There is no clear indication that jet lag and game time affect team performance when appropriate analyses are performed in a causal inference framework. Similarly, rigorous analysis should be undertaken to confirm or refute other assumptions in sport science, such as workload management, sleep practices, and dietary/supplementation regimens.
SARS-CoV-2 lineage-specific disease symptoms and disease severity in São Caetano do Sul city, Brazil
Authors: Sales Flavia Cristina da Silva , Prete Carlos Augusto , Abade Leandro , Buss Lewis Fletcher , Candido Darlan da Silva , Claro Ingra Morales , Moreira Filipe Romero Rebello , Manulli Erika Regina , Capuani Ligia , Maia Camila Alves da Silva , Oliveira Beatriz Araujo , Coletti Thais , Paiao Heuder Gustavo Oliveira , Costa Silvia Figueiredo , Correa Maria Cassia Mendes , Leal Fabio Eudes , Parag Kris Varun , Nascimento Vítor Heloiz , Faria Nuno Rodrigues , Sabino Ester Cerdeira 
Published: October 2023

AbstractBackgroundThe city of São Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic.MethodsWe selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform.ResultsMost infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts.DiscussionOur study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.
Handgrip strength as a screening tool for diabetes in resource-constrained settings: a potential solution to overcome barriers to diagnosis
Authors: Ojulari Lekan Sheriff , Sulaiman Swabirah Enimire , Ayinde Taofeek Olanrewaju , Kadir Eniola Riskat 
Published: October 2023

AbstractBackground InformationDiabetes mellitus is an escalating global health concern, especially in low and middle-income countries. The high cost and inaccessibility of diagnostic tools in resource-constrained settings have heightened the need for alternative screening methods. Handgrip strength (HGS), a measure of muscle strength, emerges as a potential non-invasive and affordable screening tool for diabetes, particularly in areas with limited healthcare access.ObjectiveTo investigate the relationship between handgrip strength and blood glucose regulation in non-diabetic young adults and to provide valuable insights into the potential of handgrip strength as a preventive and affordable approach to managing diabetes.MethodsA cross-sectional study was conducted involving 59 students (aged 18-21) from the University of Ilorin, Nigeria. Handgrip strength was measured using a dynamometer, and its relationship with blood glucose regulatory markers, such as fasting blood glucose, 2-hour post-prandial glucose, and HbA1c, was analyzed. Multiple regression models were utilized to examine the potential associations.ResultsFindings revealed significant associations between HGS and glucose regulation markers, particularly FBS, among males. In females, the relationship was evident only after adjusting for body mass index (BMI). Furthermore, a notable relationship between HGS and 2-hour post-prandial glucose levels was observed in females but not in males. However, no significant associations were found between HGS and serum insulin levels across genders.ConclusionOur study introduces HGS as a practical and cost-effective screening tool for blood glucose regulation disorders, aligning with existing literature and offering a personalized approach to management. In resource-constrained settings, HGS becomes significant, addressing diagnostic barriers and potentially revolutionizing diabetes management. However, limitations include a small sample size of 59 students and restrictions to specific demographics, emphasizing the need for future studies in diverse populations to validate HGS’s efficacy in real-world, resource-constrained settings.
Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in Non-Small Cell Lung Cancer
Authors: Hummelink Karlijn , van der Noort Vincent , Muller Mirte , Schouten Robert D. , van den Heuvel Michel M. , Thommen Daniela S. , Smit Egbert F. , Meijer Gerrit A. , Monkhorst Kim 
Published: October 2023

AbstractBackgroundTreatment with PD-(L)1 blocking agents has demonstrated durable efficacy in advanced NSCLC, but only in a minority of patients. Multiple biomarkers for predicting treatment benefit have been investigated, but their combined performance has not been extensively studied. Here, we assess the combined predictive performance of multiple biomarkers in a series of NSCLC patients treated with nivolumab.MethodsPretreatment samples from 135 patients treated with nivolumab were used to assess the predictive performance of CD8 tumor-infiltrating lymphocytes (TILs), intratumoral (IT) localization of CD8 TILs, PD-1 high expressing TILs (PD1TTILs), CD3 TILs, CD20 B-cells, tertiary lymphoid structures (TLS), PD-L1 tumor proportion score (TPS) and the Tumor Inflammation score (TIS). Patients were assigned to a training (n=55) and validation set (n=80). The primary outcome measure was Disease Control at 6 months (DC 6m) and the secondary outcome measure was DC at 12 months (DC 12m).ResultsIn the validation cohort, the two best performing composite biomarkers (i.e. CD8+IT-CD8 and CD3+IT-CD8) demonstrated similar or lower sensitivity (64% and 83%) and NPV (76% and 85%) than the individual biomarkers PD-1TTILs and TIS (sensitivity: 72% and 83%, NPV: 86% and 84%) for DC 6m, respectively. Also, at 12 months, both selected composite biomarkers (CD8+IT-CD8 and CD8+TIS) showed less predictive performance compared to PD-1TTILs and TIS alone. PD-1TTILs and TIS showed high sensitivity (86% and 100%) and NPV (95% and 100%) for DC 12m. PD-1TTILs could better discriminate patients with no long-term benefit, since specificity was substantially higher as compared to TIS (74% versus 39%).ConclusionComposite biomarkers did not show improved predictive performance compared to PD-1TTILs and TIS alone for both the 6- and 12-months endpoint. PD-1TTILs and TIS identified patients with DC 12m with high sensitivity. Patients with no long-term benefit to PD-1 blockade were most accurately identified by PD-1TTILs.
Enrichment of the local synaptic translatome for genetic risk associated with schizophrenia and autism spectrum disorder
Authors: Clifton Nicholas E , Lin Julie Qiaojin , Holt Christine E , O’Donovan Michael C , Mill Jonathan 
Published: October 2023

AbstractBackgroundGenes encoding synaptic proteins or mRNA targets of the RNA binding protein, Fragile X mental retardation protein (FMRP), have been linked to schizophrenia and autism spectrum disorder (ASD) through the enrichment of genetic variants conferring risk to these disorders. FMRP binds many transcripts with synaptic functions and is thought to be a key regulator of their local translation, a process which enables rapid and compartmentalized protein synthesis required for development and plasticity.MethodsHere, we used summary statistics from large-scale genome-wide association studies to test the hypothesis that the subset of synaptic genes encoding localized transcripts is more strongly associated with schizophrenia and ASD than non-localized transcripts. We also postulated that this subset of synaptic genes is responsible for associations attributed to FMRP targets.ResultsWe show that schizophrenia associations were enriched in genes encoding localized synaptic transcripts compared to the remaining synaptic genes, or to the remaining localized transcripts; this also applied to ASD associations, although only for transcripts observed after stimulation by fear conditioning. The genetic associations with either disorder captured by these gene sets were independent of those derived from FMRP targets. Furthermore, we found that schizophrenia association was related to FMRP interactions with mRNAs in somata, but not in dendrites, whilst ASD association was related to FMRP binding in either compartment.ConclusionsOur data suggest that synaptic transcripts capable of rapid and compartmentalized local translation are particularly relevant to the pathogenesis of schizophrenia and ASD, but do not characterize the associations attributed to current sets of FMRP targets.
Dynamics of Hepatitis C Virus Seroprevalence: Evaluating Risk Factors among Sex Workers in Pakistan
Authors: Tirmizi Raza , Rashid Rida , Zaidi Nousheen 
Published: October 2023

AbstractThe current study investigates the seroprevalence of the Hepatitis C Virus (HCV) among sex workers in Pakistan, a challenging task due to social and cultural barriers. Our primary objectives were to gauge the extent of HCV exposure in this marginalized group, identify disparities in seroprevalence between sexes, and examine the association between seropositivity and various demographic and risk factors. A total of 1,000 participants were enrolled, with male sex workers comprising the majority (87.7%) and female sex workers accounting for 12.3%. Notably, a significant portion fell within the 26-35 age category (39.9%). A significant proportion (47.1%) had not received formal education. Overall, HCV antibodies were found in 15% of the participants. Disparities were evident, with a seroprevalence of 13% in male sex workers and a significantly higher 31% in female sex workers. HCV seropositivity increased with age, with female sex workers showing a sharper rise. A link between levels of formal education and HCV seroprevalence was observed, with female sex workers consistently exhibiting higher seroprevalence across educational levels. Risk factors such as shaving practices, blade sharing, surgical history, and other medical exposures were assessed, revealing higher HCV seropositivity rates among those exposed, especially pronounced among female participants. This research study paves the way for future investigations and interventions tailored to this population’s unique needs and vulnerabilities.
Active Suppression of the Nigrostriatal Pathway during Optogenetic Stimulation Revealed by Simultaneous fPET/fMRI
Authors: Haas Sabrina , Bravo Fernando , Ionescu Tudor M. , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Dunkel Gina , Kuebler Laura , Hahn Andreas , Lanzenberger Rupert , Weigelin Bettina , Reischl Gerald , Pichler Bernd J. , Herfert Kristina 
Published: October 2023

AbstractThe dopaminergic system is a central component of the brain’s neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders such as Parkinson’s disease and schizophrenia. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine transmission from the substantia nigra to the striatum, a connection that is vital to understanding many of the disease-related dysfunctions. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the simultaneous use of [18F]FDG functional positron emission tomography (fPET)/BOLD-fMRI provided a new insight that allowed us to demonstrate an active suppression of the nigrostriatal activity during optogenetic stimulation via presynaptic autoinhibition. Ourin vivoobservation emphasizes that the observed BOLD signal depression during neuronal stimulation does not correlate with neuronal inactivity, but results from an active suppression of neuronal firing as shown by the high [18F]FDG signal increase. This result not only illustrates the potential of simultaneous fPET/fMRI to understand the molecular mechanisms of brain function but also provides a new perspective on how neurotransmitters such as dopamine influence hemodynamic responses in the brain.
A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice
Authors: Li Chunyang , Miao Cheng , Ge Yao , Wu Jiaxing , Gao Panpan , Yin Songlin , Zhang Pei , Yang Hongbin , Tian Bo , Chen Wenqiang , Chen Xiaoqian 
Published: October 2023

AbstractBackgroundThe periaqueductal gray (PAG) is a central hub for regulation of aggression, while little is known on the circuitry and molecular mechanisms that govern this regulation. We investigate the role of a distinct cell type,Tachykinin 2-expressing (Tac2+) neurons, located in the dorsomedial PAG (dmPAG), in modulating aggression in mice.MethodsWe combined activity mapping,in vivoCa2+recording, chemogenetic and pharmacological manipulation, and a viral-based translating ribosome affinity purification (TRAP) profiling using a mouse resident-intruder model.ResultsWe reveal that the dmPAGTac2neurons were selectively activated during fighting behaviors. Activation of the dmPAGTac2neurons evoked, while inhibition or genetic ablation of the dmPAGTac2neurons suppressed fighting behaviors. TRAP profiling of dmPAGTac2neurons revealed that fighting behaviors specifically induced enrichment of serotonin-associated transcripts to the dmPAGTac2neurons. Last, we validated these findings by selectively delivering pharmacological agent into the dmPAG and reversed the behavioral outcomes induced by chemogenetic manipulation.ConclusionsWe identify that the dmPAGTac2neuron can regulate mouse aggressive behavior and thus suggest a distinct molecular target for the treatment of exacerbated aggressive behaviors in populations that exhibit high-level of violence.
Social Context and Reward Sensitivity Enhance Corticostriatal Function during Experiences of Shared Rewards
Authors: Zaff Ori , Wyngaarden James B. , Dennison Jeffrey B. , Sazhin Daniel , Chein Jason , McCloskey Michael , Alloy Lauren B. , Jarcho Johanna M. , Smith David V. , Fareri Dominic S. 
Published: October 2023

AbstractAlthough prior research has demonstrated enhanced striatal response when sharing rewards with close social connections, less is known about how individual differences affect ventral striatal (VS) activation and connectivity when experiencing rewards within social contexts. Given that self-reported reward sensitivity and level of substance use have been associated with differences in VS activation, we set out to investigate whether these factors would be independently associated with enhancements to neural reward responses within social contexts. In this pre-registered study, participants (N=45) underwent fMRI while playing a card guessing game in which correct or incorrect guesses resulted in monetary gains and losses that were shared evenly with either a close friend, stranger (confederate), or non-human partner. Consistent with our prior work, we found increased VS activation when sharing rewards with a socially close peer as opposed to an out-of-network stranger. As self-reported reward sensitivity increased, the difference in VS response to rewards shared with friends and strangers decreased. We also found enhanced connectivity between the VS and temporoparietal junction when sharing rewards with close friends as opposed to strangers. Finally, exploratory analyses revealed that as reward sensitivity and sub-clinical substance use increase, the difference in VS connectivity with the right fusiform face area increases as a function of social context. These findings demonstrate that responsivity to the context of close friends may be tied to individual reward sensitivity or sub-clinical substance use habits; together these factors may inform predictions of risk for future mental health disorders.
Microbiome-Derived Prion-Like Proteins and Their Potential to Trigger Cognitive Dysfunction
Authors: Seira Curto Jofre , Dominguez Martinez Adan , Sotillo Sotillo Paula , Serrat Garcia Martina , Girona del Pozo Monica , Fernandez Maria Rosario , Sanchez de Groot Natalia 
Published: October 2023

AbstractOur life is intricately connected to microorganisms through infection or symbiotic relationships. While the inter-species propagation of prion-like proteins is well-established, their presence in the microbiome and impact on the host remains largely unexplored. To address this, we conducted a systematic study integratingin silico,in vitro,andin vivoanalyses, showing that 63% of the gastrointestinal tract microbiome encodes prion-like sequences. These sequences can form amyloid fibrils capable of interfering with the aggregation of the Amyloid-beta-peptide and promoting the aggregation and propagation of the Sup35 prion. Finally, whenC. eleganswere fed with bacteria expressing chimeras of our prion candidates, it resulted in the loss of sensory memory, reproducing the Alzheimer’s model phenotype. In our model, memory impairment is linked to aggregate fragmentation and its susceptibility to degradation. Taken together, these findings show that the gut microbiota serves as a potential reservoir of prion-like sequences, supporting the idea that microbial products may influence the pathogenesis of neurodegenerative diseases.