bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of SARS-CoV-2 Antibodies among vaccinated and non-vaccinated adults in the West Bank: Results of a repeated cross-sectional study
Authors: Awartani Faisal , Qutob Nouar , Asia Mohammad 
Published: May 2022

ABSTRACTBackgroundSeroprevalence studies provide an accurate measure of SARS-CoV-2 spread at a population level and the number of undiagnosed individuals. Repeated cross-sectional sero-studies are encouraged to monitor the spread of the virus. The aim of this study is to assess the seroprevalence rate among a random sample of Palestinians residing in the West Bank region of Palestine.MethodsThis second round cross-sectional study involved 1451 participants, who agreed to be interviewed and answer the questionnaire, where 910 of them agreed to participate in the sero- study and donate a blood sample to be tested for antibodies. The sample was randomly selected from the adult population, 18 years or older, living the West Bank region of Palestine.Serological tests for 910 adequate serum samples were done using immunoassays for detection of antibodies against SARS-CoV-2. Sociodemographic information and medical history data was collected.ResultsStudy findings indicate that as of October 2021, a seroprevalence rate of 75.9% (30% due to infection with Covid-19 virus and 45.9% due to vaccination), 95% CI (73.1-78.7). The results indicate that the prevalence of antibodies among those who are unvaccinated and undiagnosed was 45.2% with 95% CI (39.9-50.5%).The average age of participants was 37.6 years old. 49.2% were females and 50.8% were males. In relation to COVID-19, 13.6% of respondents reported getting infected by Covid-19 with statistically significant difference (P_value=0.001) between males (10.7%) and females (16.5%).. In terms of vaccination, 52.8% of respondents reported getting vaccinated with an important difference between males (64.3%) and females (40.9%), (P-value=0.000).ConclusionOur findings reveal a drastic rise in seroprevalence of SARS-CoV-2 antibodies due to infection and vaccination. This information is useful for assessing the degree of herd immunity among the adult population and provides better understanding of the pandemic. Population-based seroprevalence studies should be conducted periodically to monitor the SARS-CoV-2 seroprevalence in Palestine and inform policymakers about the efficacy of the surveillance system and the public compliance with vaccination policies especially among females
Associations between vitamin D and disease risk may be attributed to the confounding influence of adiposity during childhood and adulthood: a lifecourse Mendelian randomization study
Authors: Richardson Tom G , Power Grace M , Smith George Davey 
Published: May 2022

AbstractBackgroundVitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation.MethodsIn this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse.ResultsUsing data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range=8.9 to 11.5 years) after accounting for the effect of the adult body size genetic score (Beta=-0.32, 95% CI=-0.54 to -0.10, P=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range=40 to 69 years) is putatively mediated along the causal pathway involving adulthood adiposity (Beta=-0.17, 95% CI=-0.21 to -0.13, P=4.6×10−17).ConclusionsOur findings have important clinical implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies.
Evidence for a common mechanism supporting invigoration of action selection and action execution
Authors: Kita Kahori , Du Yue , Haith Adrian M. 
Published: May 2022

AbstractThe speed, or vigor, of our movements can vary depending on circumstances. For instance, the promise of a reward leads to faster movements. Reward also leads us to move with a lower reaction time, suggesting that the process of action selection can also be invigorated by reward. It has been proposed that invigoration of action selection and of action execution might occur through a common mechanism, and thus these aspects of behavior might be coupled. To test this hypothesis, we asked participants to make reaching movements to “shoot” through a target at varying speeds to assess whether moving more quickly was also associated with more rapid action selection. We found that, when participants were required to move with a lower velocity, the speed of their action selection was also significantly slowed. This finding was recapitulated in a further dataset in which participants determined their own movement speed, but had to move slowly in order to stop their movement inside the target. By re-analyzing a previous dataset, we also found evidence for the converse relationship between action execution and action selection: when pressured to select actions more rapidly, people also executed movements with higher velocity. Our results establish that invigoration of action selection and action execution vary in tandem with one another, supporting the hypothesis of a common underlying mechanism.Significance statementWe show that voluntary increases in the vigor of action execution lead action selection to also occur more rapidly. Conversely, hastening action selection by imposing a deadline to act also leads to increases in movement speed. These findings provide evidence that these two distinct aspects of behavior are modulated by a common underlying mechanism.
Demonstrating multi-country calibration of a tuberculosis model using new history matching and emulation package - hmer
Authors: Scarponi Danny , Iskauskas Andrew , Clark Rebecca A , Vernon Ian , McKinley Trevelyan J. , Goldstein Michael , Mukandavire Christinah , Deol Arminder , Weerasuriya Chathika , Bakker Roel , White Richard G , McCreesh Nicky 
Published: May 2022

AbstractInfectious disease models are widely used by epidemiologists to improve the understanding of transmission dynamics and disease natural history, and to predict the possible effects of interventions. As the complexity of such models increases, however, it becomes increasingly challenging to robustly calibrate them to empirical data. History matching with emulation is a calibration method that has been successfully applied to such models, but has not been widely used in epidemiology partly due to the lack of available software. To address this issue, we developed a new, user-friendly R package hmer to simply and efficiently perform history matching with emulation. In this paper, we demonstrate the first use of hmer for calibrating a complex deterministic model for the country-level implementation of tuberculosis vaccines to 115 low-and middle-income countries. The model was fit to 9–13 target measures, by varying 19–22 input parameters. Overall, 105 countries were successfully calibrated. Among the remaining countries, hmer visualisation tools, combined with derivative emulation methods, provided strong evidence that the models were misspecified and could not be calibrated to the target ranges. This work shows that hmer can be used to simply and rapidly calibrate a complex model to data from over 100 countries, making it a useful addition to the epidemiologist’s calibration tool-kit.
Developing a predictive model for an emerging epidemic on cassava in sub-Saharan Africa
Authors: Godding David , Stutt Richard O. J. H. , Alicai Titus , Abidrabo Phillip , Okao-Okuja Geoffrey , Gilligan Christopher A. 
Published: May 2022

AbstractThe agricultural productivity of smallholder farmers in sub-Saharan Africa (SSA) is severely constrained by pests and pathogens, impacting economic stability and food security. Since 2004, an epidemic of cassava brown streak disease (CBSD) has been spreading rapidly from Uganda, with the disease causing necrosis of the edible root tissue. Based on sparse surveillance data, the epidemic front is currently believed to be at least as far west as central DRC and as far south as Zambia. The DRC is the world’s highest per capita consumer of cassava and future spread threatens production in West Africa which includes Nigeria, the world’s largest producer of cassava. Here, we take a unique Ugandan CBSD surveillance dataset spanning 2004 to 2017 and develop, parameterise, and validate a landscape-scale, spatiotemporal epidemic model of CBSD at a 1 km2 resolution. While this paper focuses on Uganda, the model is designed to be readily extended to make predictions beyond Uganda for all 32 major cassava producing countries of SSA, laying the foundations for a tool capable of informing strategic policy decisions at a national and regional scale.
Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14thcentury
Authors: Waldman Shamam , Backenroth Daniel , Harney Éadaoin , Flohr Stefan , Neff Nadia C. , Buckley Gina M. , Fridman Hila , Akbari Ali , Rohland Nadin , Mallick Swapan , Nistal Jorge Cano , Yu Jin , Barzilai Nir , Peter Inga , Atzmon Gil , Ostrer Harry , Lencz Todd , Maruvka Yosef E. , Lämmerhirt Maike , Rutgers Leonard V. , Renson Virginie , Prufer Keith M. , Schiffels Stephan , Ringbauer Harald , Sczech Karin , Carmi Shai , Reich David 
Published: May 2022

AbstractWe report genome-wide data for 33 Ashkenazi Jews (AJ), dated to the 14thcentury, following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genetically similar to modern AJ and have substantial Southern European ancestry, but they show more variability in Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried the same nearly-AJ-specific mitochondrial haplogroup and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. However, the Erfurt bottleneck was more severe, implying substructure in medieval AJ. Together, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14thcentury and highlight late medieval genetic heterogeneity no longer present in modern AJ.
In vitrogeneration of human embryonic stem cell-derived heart organoids possessing physiological ion currents
Authors: Lee Jiyoung , Matsukawa Hiroshi , Sawada Kohei , Kaneko Rin , Ishino Fumitoshi 
Published: May 2022

AbstractRecently, methods forin vitroorganogenesis have been broadly developed due to their strong potential for human applications in medicine. In the present study, we optimized the culturing method of human heart organoids (hHOs) from embryonic stem cells (ESCs) in the presence of the highly concentrated laminin-entactin and fibroblast growth factor 4. The resulting hHOs showed distinctive cardiac morphology with atrium- and ventricle-like chambers composed of cardiac cells as well as expressed the integral proteins of gap junctions and ion channels. In fact, isolated cardiomyocytes from these hHOs exhibited Na and Ca currents by patch clamp analysis. These results indicated that the present method will provide a powerful tool for cardiac safety assessment of newly developed drugs as anin vitrohuman ESC-derived test system.One-Sentence SummaryFGF4 and ECM contribute to the generation of human HOs with heart compartments and electrophysiological properties.
Trimethylamine N-oxide reduces neurite density and plaque intensity in a murine model of Alzheimer’s disease
Authors: Zarbock Katie R. , Han Jessica H. , Singh Ajay P. , Thomas Sydney P. , Bendlin Barbara B. , Denu John M. , Yu John-Paul J. , Rey Federico E. , Ulland Tyler K. 
Published: May 2022

ABSTRACTBackgroundAlzheimer’s disease (AD) is the most common aging-associated neurodegenerative disease; nevertheless, the etiology and progression of the disease is still incompletely understood. We have previously shown that the microbially-derived metabolite trimethylamine N-oxide (TMAO) is elevated in the cerebrospinal fluid (CSF) of individuals with cognitive impairment due to AD and positively correlates with increases in CSF biomarkers for tangle, plaque, and neuronal pathology.ObjectiveWe assessed the direct impact of TMAO on AD progression.MethodsTo do so, transgenic 5XFAD mice were supplemented with TMAO for 12 weeks.ResultsOral TMAO administration resulted in significantly reduced neurite density in several regions of the brain, as assessed through quantitative brain microstructure imaging with neurite orientation dispersion and density imaging (NODDI) magnetic resonance imaging (MRI). Amyloid-β plaque mean intensity was reduced, while plaque count and size remained unaltered. Proteomics analysis of the cortex revealed that TMAO treatment impacted the expression of 31 proteins (1.5-fold cut-off) in 5XFAD mice, including proteins known to influence neuronal health and amyloid-β precursor protein processing. TMAO treatment did not alter astrocyte and microglial response (as determined by histological analysis) nor cortical synaptic protein expression.ConclusionThese data suggest that elevated plasma TMAO impacts AD pathology via reductions in neurite density.
Genomic insights into the adaptive and convergent evolution of Leuciscus waleckii inhabiting extremely alkaline environments
Authors: Zhou Zhixiong , Yang Junyi , Lv Hongzao , Zhou Tao , Zhao Ji , Bai Huaqiang , Pu Fei , Xu Peng 
Published: May 2022

AbstractLeuciscus waleckii is widely distributed in Northeast Asia and has high economic value. Different from its freshwater counterparts, the population in Lake Dali Nur has a strong alkalinity tolerance and can adapt to extremely alkaline–saline water with bicarbonate over 50 mmol/L (pH 9.6), thus providing an exceptional model with which to explore the mechanisms of adaptive evolution under extreme alkaline environments. Here, we assembled a high quilty chromosome-level reference genome for L. waleckii from Lake Dali Nur, which provides an important genomic resource for the exploitation of alkaline water fishery resources and adaptive evolution research across teleost fish. Notably, we identified significantly expanded long terminal repeats (LTRs) and long interspersed nuclear elements (LINEs) in L. waleckii compared to other Cypriniformes fish, suggesting their more recent insertion into the L. waleckii genome. We also identified expansions in genes encoding gamma-glutamyltransferase, which possibly underlie the adaptation to extreme environmental stress. Based on the resequencing of 85 L.waleckii individuals from divergent populations, the historical population size of L.waleckii in Lake Dali Nur dramatically expanded in a thousand years approximately 13,000 years ago, and experienced a cliff recession in the process of adapting to the alkaline environment of Lake Dali Nur approximately 6,000 years ago. Genome scans further revealed the significant selective sweep regions from Lake Dali Nur, which harbour a set of candidate genes involved in hypoxia tolerance, ion transport, acid-base regulation and nitrogen metabolism. In particular, 5 alkali population specific nonsynonymous mutations were identified in CA15 gene copies. In addition, two sites with convergent amino acid mutation were detected in the RHCG-a gene among several alkali environment adapted Cypriniformes fish, this mutation may increase the NH3 excretion rate of the RHCG channel. Our findings provide comprehensive insight into the genomic mechanisms of L. waleckii and reveal their adaptative evolution under extreme alkaline environments.
Interneurons of fan-shaped body promote arousal in Drosophila
Authors: Kato Yoshiaki S. , Tomita Jun , Kume Kazuhiko 
Published: May 2022

AbstractSleep is required to maintain physiological functions and is widely conserved across species. To understand the sleep-regulatory mechanisms, sleep-regulating genes and neuronal circuits are studied in various animal species. In the sleep-regulatory neuronal circuits in Drosophila melanogaster, the dorsal fan-shaped body (dFB) is a major sleep-promoting region. However, other sleep-regulating neuronal circuits were not well identified. We recently found a novel sleep-regulatory circuit consisting of arousal-promoting T1 dopamine neurons and protocerebral bridge (PB) neurons innervating the ventral part of the FB, which we named “the PB-FB pathway”. However, the post-synaptic target of the PB-FB pathway was still unknown. To identify it, we performed anterograde tracing, immunohistochemistry, and Ca2+ imaging analysis and found that the PB-FB pathway projects to FB interneurons, also known as pontine neurons. Besides, we found that cholinergic pontine neurons promote arousal. Moreover, we indicated that pontine neurons form an anatomical connection with sleep-promoting dFB neurons. Together, we showed that pontine neurons receive excitatory signals from the PB-FB pathway and cholinergic pontine neurons promote arousal. These results completed one of the output pathways from the PB-FB pathway.
Deep phenotyping of women with endometriosis-associated pain and bladder pain syndrome: the TRiPP (Translational Research in Pelvic Pain) study protocol
Authors: Demetriou Lysia , Coxon Lydia , Krassowski Michal , Rahmioglu Nilufer , Arendt-Nielsen Lars , Aziz Qasim , Becker Christian M. , Birch Judy , Cruz Franscisco , Hoffman Anja , Horne Andrew W. , Hummelshoj Lone , McMahon Stephen , Meijlink Jane , Pogatzki-Zahn Esther , Sieberg Christine B. , Tracey Irene , Treede Rolf-Detlef , Missmer Stacey A. , Zondervan Krina T. , Nagel Jens , Vincent Katy 
Published: May 2022

AbstractObjectivesChronic pelvic pain is common, poorly understood, and many women suffer for years without proper diagnosis and effective treatment. The Translational Research in Pelvic Pain (TRiPP) project takes a phenotyping approach, with a particular focus on endometriosis-associated pain (EAP) and bladder pain syndrome (IC/BPS), to improve our fundamental understanding of chronic pelvic pain. We believe that reconceptualising these conditions in the context of the multisystem dysfunction known for other chronic pain conditions rather than as end-organ pathologies has the potential to improve our understanding of the conditions. Our approach combines clinical, biological, physiological and psychological data to establish perturbations in the functions of pain-relevant systems that are specific to EAP and IC/BPS, and those that overlap both conditions and chronic pelvic pain more generally and associated quantitative biomarker profiles.DiscussionWe believe that TRiPP’s novel methodological approach will produce clinical data to aid our understanding of pelvic pain and identify underlying pathways for the development of refined animal models and targeted therapeutic treatments.
Rare Gli1+ perivascular fibroblasts promote skin wound repair
Authors: Sun Xiaoyan , Annusver Karl , Dalessandri Tim , Kasper Maria 
Published: May 2022

ABSTRACTGrowing evidence suggests that perivascular cells play important roles in tissue repair of various organs. In the skin, the contribution and importance of these cells for wound repair is not resolved. Here we demonstrate that a specific Gli1+ subpopulation residing in the perivascular niche serves as an important cellular source for wound healing fibroblast. First, we show that Gli1 expression marks small subsets of both pericytes and perivascular adventitial cells. Upon injury both cell types rapidly responded already within their original niche, however only the progeny of Gli1+ adventitial cells expanded and differentiated into wound-contracting myofibroblasts. Genetic ablation of these cells significantly impaired wound healing, which was associated with the reduction of aSMA+ myofibroblast-mediated wound contraction. After wound closure these cells reverted to an aSMA-negative fibroblast state, and intriguingly, they persisted in wounds over long term and adopted a non-fibrotic fibroblast signature. In sum, our data sheds new light on the functional diversity of perivascular-cell subtypes in the skin, and proposes a new mesenchymal cell source that promotes wound healing.
Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation
Authors: Dikiy Stanislav , Levine Andrew G. , Giovanelli Paolo , Wang Zhong-Min , Beroshvili Giorgi , Pritykin Yuri , Krishna Chirag , Glasner Ariella , Leslie Christina S. , Rudensky Alexander Y. 
Published: May 2022

AbstractRegulatory T (Treg) cells represent a specialized CD4+T cell lineage with essential anti-inflammatory functions. Recent studies of the adaptations of Treg cells to non-lymphoid tissues which enable their specialized immunosuppressive and tissue supportive functions raise questions about the underlying mechanisms of these adaptations and whether they represent stable differentiation or reversible activation states. Using novel genetic tools, we characterized the transcriptional programs of distinct colonic effector Treg cell types. We found that attenuated T cell receptor (TCR) signaling and acquisition of substantial TCR independent functionality appears to facilitate the terminal differentiation of a population of colonic effector Treg cells distinguished by stable expression of immunomodulatory cytokine interleukin-10 (IL-10). Functional studies revealed that this subset of effector Treg cells, but not their expression of IL-10, was indispensable for colonic health. These findings suggest core features of terminal differentiation of effector Treg cells in non-lymphoid tissues and their function therein.
Cheaters among pollinators: Floral traits drive spatiotemporal variation in nectar robbing and thieving in Afrotropical rainforests
Authors: Sakhalkar Sailee P. , Janeček Štěpán , Klomberg Yannick , Mertens Jan E.J. , Hodeček Jiří , Tropek Robert 
Published: May 2022

SUMMARYNectar robbing and thieving can substantially affect the reproduction of animal-pollinated plants. Although the intensity of nectar exploitation remains unexplored at the community level, it probably varies along environmental gradients.We video-recorded flower visits to animal-pollinated plants in Afrotropical rainforests along a complete elevational gradient in the wet and dry seasons on Mount Cameroon. We analysed how the proportion of nectar robbing and thieving in the communities changes spatiotemporally, especially in association with the floral traits of the flowering plants.We recorded 14,391 flower visits, of which ~4.3% were from robbers (mostly bees and birds), and ~2.1% were from thieves (mostly flies, bees, and moths). Of the 194 studied plants, only 29 and 39 were nectar robbed and thieved, respectively. Robbers and thieves were most frequent at mid-elevations, with more frequent robbing in the wet season and thieving in the dry season. These trends were linked to the local composition of floral traits, and cheating groups’ associations to particular traits. Floral traits that prevented thieving made flowers susceptible to robbing, and vice versa.Spatiotemporal variation in floral traits across drives the cheating behaviour of flower visitors across communities, while indicating a trade-off between preventing nectar robbing and thieving.