bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D status and cardiometabolic disease risk among healthy adults of Northern Ghana
Authors: Bawah Abdul-Malik , Annan Reginald A. , Ellahi Basma , SanthanakrishnanVimaleswaran Karani , Haadi Abdul Rahman 
Published: November 2022

AbstractCardiometabolic Disease (CMD) is a cluster of conditions that increase the risk for cardiovascular events, but its relationship with vitamin D status has not been studied in Ghana. A cross-sectional study design was conducted to investigate the relationship between serum vitamin D status and CMD risk (obesity, type 2 diabetes mellitus, hypertension, and dyslipidemia) among 302 apparently healthy adults, aged 25 to 59 and of northern decent in Ghana. Biochemical analysis was done to determine serum total cholesterol (TC), Triglycerides (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Fasting Blood Glucose (FBG), Glycated Haemoglobin (HbA1c) and serum vitamin D levels of participants. Anthropometric assessment was also done and BMI, WC, HC, Blood Pressure, WHR, Body Fat (BF) and visceral fat percentages were obtained. Analysis was done using SPSS (version 25). We evaluated CMD risk factors to predict vitamin D status using binary and multiple linear logistics regression analysis. Similar between gender, participants’ mean age was 38.78years (SD 10.42years). The females had higher BMI (24.31 SD 7.96 versus 22.52 SD 3.07 kgm2, p=0.006), % total body fat (24.31 SD 7.96 versus 22.52 SD 3.07%, p=0.001), WC (24.31 SD 7.96 versus 22.52 SD 3.07 inches, p=0.002), and HC (24.31 SD 7.96 versus 22.52 SD 3.07, p=0.002 inches) than the males, while the males had higher mean total cholesterol (5.74SD1.02 versus 3.57SD1.02) and LDL (5.40SD1.05, verse 3.22SD1.09, p=0.005) than the females. Serum vitamin D levels was significantly associated with age (p= 0.047) but not gender (p=0.349). Overall, 6.4% of participants had CMD, representing 10.2% of the females, and no male. Multivariate analysis reveals gender, average BP, FBG, and % total body fat to significantly affect serum vitamin D concentrations. Seven percent (7%) of participants were serum vitamin D deficient (VDD) and 28.5% had serum vitamin D insufficiency (VDI), similar by gender, but increased with age (p=0.047). Both mean SBP (P<0.0001) and DBP (p<0.0001) increased with VDD, while means of FBS (p=0.032), BMI (p=0.004), HbA1c (p=0.040), and LDL (p=0.047) are highest in the VDD group and least in the Vitamin D Sufficient (VDS) group. Binary Logistic regression showed participants with high SBP (OR= 0.055; 95% CI= 0.008-0.361; p= 0.003) and high FBS (OR= 0.076; 95% CI= 0.014-0.404; p= 0.002) had increased odds of VDD compared with normal levels of SBP and FBS. Multiple logistics regression showed FBG, TG, LDL and WC significantly predicted CMD. In conclusion, CMD risk factors were common among the participants and more than a third were vitamin D deficient or insufficient. Individual CMD risk factors increased with vitamin D deficiency, but CMD did not predict serum vitamin D status.
Pleiotropic Loci for Cannabis Use Disorder Severity in Multi-Ancestry High-Risk Populations
Authors: Peng Qian , Wilhelmsen Kirk C. , Ehlers Cindy L. 
Published: November 2022

ABSTRACTCannabis use disorder (CUD) is common and has in part a genetic basis. The risk factors underlying its development likely involve multiple genes that are polygenetic and interact with each other and the environment to ultimately lead to the disorder. Co-morbidity and genetic correlations have been identified between CUD and other disorders and traits in select populations primarily of European descent. If two or more traits, such as CUD and another disorder, are affected by the same genetic locus, they are said to be pleiotropic. The present study aimed to identify specific pleiotropic loci for the severity level of CUD in three high-risk population cohorts: American Indians (AI), Mexican Americans (MA), and European Americans (EA). Using a previously developed computational method based on a machine learning technique, we leveraged the entire GWAS catalog and identified 114, 119, and 165 potentially pleiotropic variants for CUD severity in AI, MA, and EA respectively. Ten pleiotropic loci were shared between the cohorts although the exact variants from each cohort differed. While majority of the pleiotropic genes were distinct in each cohort, they converged on numerous enriched biological pathways. The gene ontology terms associated with the pleiotropic genes were predominately related to synaptic functions and neurodevelopment. Notable pathways included Wnt/β-catenin signaling, lipoprotein assembly, response to UV radiation, and components of the complement system. The pleiotropic genes were the most significantly differentially expressed in frontal cortex and coronary artery, up-regulated in adipose tissue, and down-regulated in testis, prostate, and ovary. They were significantly up-regulated in most brain tissues but were down-regulated in the cerebellum and hypothalamus. Our study is the first to attempt a large-scale pleiotropy detection scan for CUD severity. Our findings suggest that the different population cohorts may have distinct genetic factors for CUD, however they share pleiotropic genes from underlying pathways related to Alzheimer’s disease, neuroplasticity, immune response, and reproductive endocrine systems.
Prolonged T-cell activation and long COVID symptoms independently associate with severe disease at 3 months in a UK cohort of hospitalized COVID-19 patients
Authors: Santopaolo Marianna , Gregorova Michaela , Hamilton Fergus , Arnold David , Long Anna , Lacey Aurora , Oliver Elizabeth , Halliday Alice , Baum Holly , Hamilton Kristy , Milligan Rachel , Pearce Olivia , Knezevic Lea , Aza Begonia Morales , Milne Alice , Milodowski Emily , Lazarus Rajeka , Goenka Anu , Finn Adam , Maskell Nick , Davidson Andrew , Gillespie Kathleen , Wooldridge Linda , Rivino Laura 
Published: November 2022

AbstractCOVID-19 causes immune perturbations which may persist long-term, and patients frequently report ongoing symptoms for months after recovery. We assessed the extent and nature of immune activation at 3 months post hospital admission in patients with mild, moderate or severe COVID-19 and investigated whether immune activation associates with disease severity and long COVID. Patients with severe disease displayed persistent activation of CD4+and CD8+T-cells, based on expression of HLA-DR, CD38, Ki67 and granzyme B, but they lacked activation of other immune subsets. Elevated plasma levels of IL-4, IL-7, IL-17 and TNF-α were present in patients with severe compared to mild and/or moderate disease. Plasma from severe patients caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that factors in the plasma of severe patients may increase T-cell responsiveness to IL-15-driven ‘bystander” activation, which may drive persistent T-cell activation after severe COVID-19. Patients with severe disease reported a higher number of long COVID symptoms which correlated with the frequency of two subsets of activated CD4+and CD8+T cells (CD4+T-cell population 2 and CD8+T-cell population 4; FDR p<0.05), however these associations were lost after adjusting for age, sex and disease severity. Our data suggests that persistent immune activation and long COVID correlate independently with severe disease.
Multifaceted quality assessment of gene repertoire annotation with OMArk
Authors: Nevers Yannis , Rossier Victor , Train Clément Marie , Altenhoff Adrian , Dessimoz Christophe , Glover Natasha 
Published: November 2022

AbstractAssessing the quality of protein-coding gene repertoires is critical in an era of increasingly abundant genome sequences for a diversity of species. State-of-the-art genome annotation assessment tools measure the completeness of a gene repertoire, but are blind to other types of errors, such as gene over-prediction or contamination.We developed OMArk, a software relying on fast, alignment-free sequence comparisons between a query proteome and precomputed gene families across the tree of life. OMArk assesses not only the completeness, but also the consistency of the gene repertoire as a whole relative to closely related species. It also reports likely contamination events.We validated OMArk with simulated data, then performed an analysis of the 1805 UniProt Eukaryotic Reference Proteomes, illustrating its usefulness for comparing and prioritizing proteomes based on their quality measures. In particular, we found strong evidence of contamination in 59 proteomes, and identified error propagation in avian gene annotation resulting from the use of a fragmented zebra finch proteome as reference.OMArk is available on GitHub (https://github.com/DessimozLab/OMArk), as a Python package on PyPi, and as an interactive online tool athttps://omark.omabrowser.org/.
Tuberculosis prevalence and incidence rates from repeated population-based screening in a district in Ethiopia: a prospective cohort study
Authors: Banti Abiot Bezabeh , Hinderaker Sven Gudmund , Winje Brita Askeland , Heldal Einar , Abebe Markos , Dangisso Mesay Hailu , Datiko Daniel Gemechu 
Published: November 2022

ABSTRACTObjectiveIn Ethiopia, a third of the estimated tuberculosis cases are not detected or reported. Incidence estimates are inaccurate and are rarely measured directly. Any tuberculosis program will miss some tuberculosis cases and assessing the ‘‘real’’ incidence under program conditions is useful to understand the situation. This study aimed to measure the prevalence and incidence of pulmonary tuberculosis based on three rounds of household visits in the adult population of Dale in Ethiopia.DesignA prospective population-based cohort study.SettingEvery household in Dale district was visited three times at 4-month interval over 12 months.ParticipantsIndividuals aged 15 and more years were followed.Outcome measuresMicroscopy smear-positive PTB (PTB s+), bacteriologically confirmed PTB (PTB b+) by microscopy, GeneXpert, or culture, and clinically diagnosed PTB (PTB c+).ResultsAmong 136,181 individuals, 2052 had presumptive TB in round1, including 93 with PTB s+, 98 with PTB b+, and 24 with PTB c+; adding those with PTB who were already on treatment, the total number of PTB was 201, and the prevalence was 147 (95%CI: 127–168)/100,000 population. Out of all detected PTB patients by screening, PTB s+ was 65%, PTB b+ was 67%, and PTB c+ was 44%. During 96,388 person-years follow-up after round1 to round3 end, 1909 had presumptive TB, 320 had PTB, and the total incidence of PTB was 332 (95%CI: 297–370)/100,000 person-years, while the incidence of PTB s+, PTB b+, and PTB c+ was 230 (95%CI: 201–262), 263 (95%CI: 232–297), and 68 (95%CI: 53–86)/100,000 person-years, respectively.ConclusionThe prevalence of PTB s+ was similar to the national survey and local studies, but only a third of prevalent PTB cases had been notified. The incidence rate was highest in those aged 25–34 years, indicating ongoing transmission. Finding missing people with TB through repeated screening can reduce transmission.Strengths and limitations of this studyThis study included a large sample and worked closely with the national tuberculosis program and the community structures that contributed to its sustainability.We report not only tuberculosis prevalence but also incidence based on three rounds of household visits, which is often not reported elsewhere.The study screened a very high proportion of households in the district, giving an accurate measure of the burden of tuberculosis, where the probability of missing people with TB is small.Tuberculosis cases notified were chosen the year before the study because we could not separate the patients identified by the screening from those who attended the health services themselves.We did not perform GeneXpert and culture for all smear-positive tuberculosis cases, so there was a difference between microscopy smear-positive and bacteriologically confirmed tuberculosis cases, which was very small.
Separating the control of moving and holding in post-stroke arm paresis
Authors: Hadjiosif Alkis M. , Kita Kahori , Albert Scott T. , Scheidt Robert A. , Shadmehr Reza , Krakauer John W. 
Published: November 2022

AbstractMoving and holding still have been posited to be under separate control regimes for both eye and arm movements. The paretic arm after stroke exhibits different abnormalities during rest vs. movement, providing an opportunity to ask whether control of these behaviors is independently affected in stroke. Here, we quantified resting postural abnormalities in stroke patients by measuring their biases in force production as they held their hand still in various locations in a planar workspace, and then assessed the influence of these resting force biases on reaching in the same workspace. We found that patients had marked resting force biases at each location, even when the arm was supported. However, these biases did not transfer to arm-supported planar reaching movements: not during initial acceleration, not in response to mid-trajectory perturbations, and not during deceleration to a stop. Rather, the abnormal resting forces only appeared to switch on after a movement had fully stopped. These findings suggest that moving and holding are functionally separable modes of control. At the same time, we found that the resting biases mirrored characteristics of abnormal synergies during movement: they markedly decreased when arm support was provided; they were higher in more distal positions which require breaking out of flexion; and they scaled with the Fugl-Meyer score for the upper extremity (a measure of intrusion of abnormal synergies during active movement). These three shared features suggest a common mechanism for resting biases and abnormal synergies, which appears to be a contradiction given the functional separation of moving and holding observed in the same patients. To resolve this paradox, we propose a conceptual model that predicts a breakdown in the functional separation between reaching and holding when patients move in the absence of weight support. This conceptual model posits that synergies are the behavioral manifestation of a spillover of posture into movement. Mapping these functional systems onto anatomical and physiological details of lesioned substrate after stroke may provide implementation-level insight into how normal arm motor control is assembled.
Auditory Brainstem Mechanisms Likely Compensate for Self-imposed Peripheral Inhibition
Authors: Peterson Abigayle , Easwar Vijayalakshmi , Powell Lindsey , Boothalingam Sriram 
Published: November 2022

AbstractIt is well known that the medial olivocochlear reflex (MOCR) in the brainstem, part of the efferent network, inhibits the cochlear active gain mechanism. The upstream neural influence of this peripheral inhibition is less understood. When the MOCR is activated, responses generated in the cochlea and cortex undergo putative attenuation, yet the amplitude of responses generated in the brainstem are perplexingly unaffected despite decreased input from the periphery. Based on known neural circuitry, we hypothesized that the inhibition of peripheral input is compensated for by equivalent positive feedback in the brainstem over time. We predicted that the inhibition can be captured at the brainstem with stimuli shorter (1.5 s) than previously employed long durations (4 min) where this inhibition is diminished due to compensation. Results from 18 normal hearing human listeners support our hypothesis in that when the MOCR is activated, there is a robust reduction of responses generated at the periphery, brainstem, and cortex for short stimuli and that brainstem inhibition diminishes for longer stimuli. Our methodology and findings have implications for auditory disorders such as tinnitus, evaluation of efferent function, and provides a novel non-invasive window into potential gain compensation mechanisms in the brainstem.
Fungal antibiotics control bacterial community diversity in the cheese rind microbiome
Authors: Tannous Joanna , Cosetta Casey M. , Drott Milton T. , Rush Tomás A. , Abraham Paul E. , Giannone Richard J. , Keller Nancy P. , Wolfe Benjamin E. 
Published: November 2022

ABSTRACTPotent antimicrobial metabolites are produced by filamentous fungi in pure lab cultures, but their ecological functions in nature are often unknown. Using an antibiotic-producingPenicilliumisolate and the cheese rind microbial community, we demonstrate that a fungal specialized metabolite can regulate the diversity of bacterial communities. Inactivation of the global regulator, LaeA, resulted in the loss of antibacterial activity in thePenicilliumisolate. Cheese rind bacterial communities assembled with thelaeAdeletion strain had significantly higher bacterial abundances than the wild-type strain. RNA-sequencing and metabolite profiling demonstrated a striking reduction in the expression and production of the natural product pseurotin in thelaeAdeletion strain. Inactivation of a core gene in the pseurotin biosynthetic cluster restored bacterial community composition, demonstrating the role of pseurotins in mediating bacterial community assembly. Our discovery demonstrates how antibiotic production can drive the assembly of microbiomes and provides an ecological context for widespread fungal specialized metabolites.
Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells
Authors: Delima Gabrielle K. , Ganti Ketaki , Holmes Katie E. , Shartouny Jessica R. , Lowen Anice C. 
Published: November 2022

AbstractWhen multiple viral populations propagate within the same host environment, they often shape each other’s dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global population level. For influenza A viruses (IAVs), the delivery of multiple viral genomes to a cell substantially increases burst size. However, despite its relevance for IAV evolution through reassortment, the implications of this positive density dependence for coinfection between distinct IAVs has not been explored. Furthermore, the extent to which these interactions within the cell shape viral dynamics at the level of the host remains unclear. Here we show that, within cells, coinfecting IAVs strongly augment the replication of a focal strain, irrespective of the native host of the coinfecting IAV or its homology to the focal strain. Coinfecting viruses with a low intrinsic reliance on multiple infection offer the greatest benefit. Nevertheless, virus-virus interactions at the level of the whole host are antagonistic. This antagonism is recapitulated in cell culture when the coinfecting virus is introduced several hours prior to the focal strain or under conditions conducive to multiple rounds of viral replication. Together, these data suggest that beneficial virus-virus interactions within cells are counterbalanced by competition for susceptible cells during viral propagation through a tissue. The integration of virus-virus interactions across scales is critical in defining the outcomes of viral coinfection.
Multiple rod layers increase the speed and sensitivity of vision in nocturnal reef fishes
Authors: Fogg Lily G. , Chung Wen-Sung , Cortesi Fabio , Marshall N. Justin , de Busserolles Fanny 
Published: November 2022

AbstractMultibank retinas have rod photoreceptors stacked into multiple layers. They are found in many species of fish that inhabit dim environments and are one of the most common visual adaptations in the deep-sea. Despite its prevalence, the function of multibank retinas remained unknown. Two predominant theories, neither of which has been tested, have emerged: 1) they enhance sensitivity in dim light, and 2) they allow colour vision in dim light. To investigate the sensitivity hypothesis, we performed electrophysiological recordings and compared the rod pigments of three species of nocturnal reef fishes, two with a multibank retina (Neoniphon sammaraandMyripristis violacea) and a control species with a single rod bank (Ostorhinchus compressus). Results indicated that nocturnal reef fishes with a multibank retina have higher temporal resolution of vision, as indicated by electrophysiology, and that their rhodopsin proteins likely also have faster retinal release kinetics, as suggested by amino acid substitutions. Electrophysiology also showed that the multibank retina conferred greater sensitivity to both dim and bright intensities than a single rod bank and this occurred at times when rod-derived signals usually dominate the visual response. This study provides the first functional evidence for enhanced dim-light sensitivity using a multibank retina while also suggesting novel roles for the adaptation in enhancing bright-light sensitivity and the speed of vision.SignificanceMost vertebrates have one layer of the dim-light active rod photoreceptors; however, some species have multiple layers, known as a multibank retina. We used electrophysiology on nocturnal reef fishes with and without multibank retinas to evaluate the sensory advantage of having multiple rod layers. We show that fish with multibank retinas have both faster vision and enhanced sensitivity to bright and dim light intensities. Thus, we resolve for the first time the function of multibank retinas – one of the most common visual adaptations in the deep sea. Our findings highlight an unconventional vertebrate visual system as well as the visual capabilities of fishes from the most vast (deep sea) and vibrant (reefs) ecosystems on the planet.
DRG afferents that mediate physiologic and pathologic mechanosensation from the distal colon
Authors: Wolfson Rachel L. , Abdelaziz Amira , Rankin Genelle , Kushner Sarah , Qi Lijun , Mazor Ofer , Choi Seungwon , Sharma Nikhil , Ginty David D. 
Published: November 2022

AbstractThe properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal disease. Here, we report genetically defined subsets of colon innervating DRG neurons with diverse morphologic and physiologic properties. Four colon innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled usingBmpr1bgenetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous mechanoreceptor populations, colon innervating DRG afferents exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon innervating HTMRs mediate pathophysiological responses to colon distension revealing a target population for therapeutic intervention.