bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 10-year review of antihypertensive prescribing practices after stroke and the associated disparities from the Florida Stroke Registry
Authors: Perue Gillian Gordon , Ying Hao , Bustillo Antonio , Zhou Lili , Gutierrez Carolina M. , Wang Kefeng , Gardener Hannah E , Krigman Judith , Jameson Angus , Foster Dianne , Dong Chuanhui , Rundek Tatjana , Rose David Z , Romano Jose G. , Alkhachroum Ayham , Sacco Ralph L. , Asdaghi Negar , Koch Sebastian 
Published: February 2023

AbstractBackgroundGuideline based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescribers’ blood pressure medication choice adheres to clinical practice guidelines (Prescribers’-Choice Adherence).MethodsThe Florida Stroke registry (FSR) utilizes statewide data prospectively collected for all acute stroke admissions. Based on established guidelines we defined optimal Prescribers’-Choice Adherence using the following hierarchy of rules: 1) use of an angiotensin inhibitor (ACEI) or angiotensin receptor blocker (ARB) as first-line antihypertensive among diabetics; 2) use of thiazide-type diuretics or calcium channel blockers (CCB) among African-American patients; 3) use of beta-adrenergic blockers (BB) among patients with compelling cardiac indication (CCI) 4) use of thiazide, ACEI/ARB or CCB class as first-line in all others; 5) BB should be avoided as first line unless CCI.RESULTSA total of 372,254 cases from January 2010 to March 2020 are in FSR with a diagnosis of acute ischemic, hemorrhagic stroke, transient ischemic attack or subarachnoid hemorrhage; 265,409 with complete data were included in the final analysis. Mean age 70 +/-14 years, 50% female, index stroke subtype of 74% acute ischemic stroke and 11% intracerebral hemorrhage. Prescribers’-Choice Adherence to each specific rule ranged from 48-74% which is below quality standards of 85%. There were race-ethnic disparities with only 49% Prescribers choice Adherence for African Americans patients.ConclusionThis large dataset demonstrates consistently low rates of Prescribers’-Choice Adherence over 10 years. There is an opportunity for quality improvement in hypertensive management after stroke.
Gut Microbiome Composition Reveals the Distinctiveness between the Bengali people and the Indigenous Ethnicities in Bangladesh
Authors: Ahammad Ishtiaque , Rahman Anisur , Chowdhury Zeshan Mahmud , Bhattacharjee Arittra , Dewan Gourab , Talukder Shiny , Das Keshob Chandra , Keya Chaman Ara , Hossain Mohammad Uzzal , Salimullah Md. 
Published: February 2023

AbstractHuman gut microbiome is influenced by ethnicity and other factors. In this study, we have explored the gut microbiome of Bengali population (n=13) and four Tibeto-Burman indigenous communities-Chakma (n=15), Marma (n=6), Khyang (n=10), and Tripura (n=11) using 16S rRNA amplicon sequencing. A total of 19 characterized phyla were identified in 5 cohorts, withFirmicutesandBacteroidetesbeing the most prevalent. At the genus level, the abundance ofPrevotellawas relatively similar across all ethnicities. However, the Chakma population demonstrated higherBacteroidesabundance. Chakma people were more distinct than other ethnicities and exhibited a higher quantity of differentially abundant microbial features. The Bengali population had relatively low bacterial richness and‘FirmicutestoBacteroidetesratio’ than others with lower qualitative microbial diversity. A phylosymbiotic link between Bangladeshi indigenous people and certain ethnic groups in India have also been discovered. A comparative analysis between all Bangladeshi samples (n=55) and several tropical and subtropical countries (n=132) such as Australia, Egypt, Indonesia, Malaysia, Mexico, Thailand, and Vietnam revealed that the gut microbiota profile of Bangladeshi people is remarkably distinct from others. The insights from this study will aid further epidemiological and translational research.
μ-PBWT: Enabling the Storage and Use of UK Biobank Data on a Commodity Laptop
Authors: Cozzi Davide , Rossi Massimiliano , Rubinacci Simone , Köppl Dominik , Boucher Christina , Bonizzoni Paola 
Published: February 2023

AbstractMotivationThe positional Burrows-Wheeler Transform (PBWT) has been introduced as a key data structure for indexing haplotype sequences with the main purpose of finding maximal haplotype matches inhsequences containingwvariation sites in-time with a significant improvement over classical quadratic time approaches. However the original PBWT data structure does not allow queries over the modern biobank panels of haplotypes consisting of several millions of haplotypes, as they must be kept entirely in memory.ResultsIn this paper, we present a method for constructing the run-length encoded PBWT for memory efficient haplotype matching. We implement our method, which we refer to asμ-PBWT, and evaluate it on datasets of 1000 Genome Project and UK Biobank data. Our experiments demonstrate that theμ-PBWTreduces the memory usage up to a factor of 25 compared to the best current PBWT-based indexing. In particular,μ-PBWTproduces an index that stores high-coverage whole genome sequencing data of chromosome 20 in half the space of its BCF file. In addition,μ-PBWTis able to index a dataset with 2 million haplotypes and 2.3 million sites in 4 GB of space, which can be uploaded in 20 seconds on a commodity laptop.μ-PBWTis an adaptation of techniques for the run-length compressed BWT for the PBWT (RLPBWT) and it is based on keeping in memory only a small representation of the RLPBWT that still allows the efficient computation of set maximal matches (SMEMs) over the original panel.AvailabilityOur implementation is open source and available athttps://github.com/dlcgold/muPBWT. The binary is available athttps://bioconda.github.io/recipes/mupbwt/README.htmlContactPaola Bonizzonipaola.bonizzoni@unimib.it
Temporal Notch signaling regulates mucociliary cell fates through Hes-mediated competitive de-repression
Authors: Brislinger-Engelhardt Magdalena Maria , Lorenz Fabian , Haas Maximilian , Bowden Sarah , Tasca Alexia , Kreutz Clemens , Walentek Peter 
Published: February 2023

AbstractTissue functions are determined by the types and ratios of cells present, but little is known about self-organizing principles establishing correct cell type compositions. Mucociliary airway clearance relies on the correct balance between secretory and ciliated cells, which is regulated by Notch signaling across mucociliary systems. Using the airway-likeXenopusepidermis, we investigate how cell fates depend on signaling, how signaling levels are controlled, and how Hes transcription factors regulate cell fates. We show that four mucociliary cell types each require different Notch levels and that their specification is initiated sequentially by a temporal Notch gradient. We describe a novel role for Foxi1 in the generation of Delta-expressing multipotent progenitors through Hes7.1. Hes7.1 is a weak repressor of mucociliary genes and overcomes maternal repression by the strong repressor Hes2 to initiate mucociliary development. Increasing Notch signaling then inhibits Hes7.1 and activates first Hes4, then Hes5.10, which selectively repress cell fates. We have uncovered a self-organizing mechanism of mucociliary cell type composition by competitive de-repression of cell fates by a set of differentially acting repressors. Furthermore, we present anin silicomodel of this process with predictive abilities.
The response time paradox in functional magnetic resonance imaging analyses
Authors: Mumford Jeanette Alane , Bissett Patrick G. , Jones Henry M. , Shim Sunjae , Rios Jaime Ali H. , Poldrack Russell A. 
Published: February 2023

AbstractThe functional MRI (fMRI) signal is a proxy for an unobservable neuronal signal, and differences in fMRI signals on cognitive tasks are generally interpreted as reflecting differences in the intensity of local neuronal activity. However, changes in either intensity or duration of neuronal activity can yield identical differences in fMRI signals. When conditions differ in response times (RTs), it is thus impossible to determine whether condition differences in fMRI signals are due to differences in the intensity of neuronal activity or to potentially spurious differences in the duration of neuronal activity. The most common fMRI analysis approach ignores RTs, making it difficult to interpret condition differences that could be driven by RTs and/or intensity. Because differences in response time are one of the most important signals of interest for cognitive psychology, nearly every task of interest for fMRI exhibits RT differences across conditions of interest. This results in a paradox, wherein the signal of interest for the psychologist is a potential confound for the fMRI researcher. We review this longstanding problem, and demonstrate that the failure to address RTs in the fMRI time series model can also lead to spurious correlations at the group level related to RTs or other variables of interest, potentially impacting the interpretation of brain-behavior correlations. We propose a simple approach that remedies this problem by including RT in the fMRI time series model. This model separates condition differences from RT differences, retaining power for detection of unconfounded condition differences while also allowing the identification of RT-related activation. We conclude by highlighting the need for further theoretical development regarding the interpretation of fMRI signals and their relationship to response times.
Scanning electron microscopy of human islet cilia
Authors: Polino Alexander J. , Sviben Sanja , Melena Isabella , Piston David W. , Hughes Jing 
Published: February 2023

ABSTRACTHuman islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like primary cilia, but conventional sample preparation does not reveal the sub-membrane axonemal structure which holds key implications for cilia function. To overcome this challenge, we combined SEM with membrane-extraction techniques to examine cilia in native human islets. Our data show well-preserved cilia subdomains which demonstrate both expected and unexpected ultrastructural motifs. Morphometric features were quantified when possible, including axonemal length and diameter, microtubule conformations and chirality. We further describe a novel ciliary ring, a structure that may be a specialization in human islets. Key findings are correlated with fluorescence microscopy and interpreted in the context of cilia function as a cellular sensor and communications locus in pancreatic islets.
Intracellular Amyloid-β in the Normal Rat Brain and Human Subjects
Authors: Kobro-Flatmoen Asgeir , Hormann Thea Meier , Gouras Gunnar 
Published: February 2023

AbstractAmyloid-beta (Aβ) is a normal product of neuronal activity, and the two most common variants are 40 or 42 residues long. Of these, the 42 residue-version (Aβ42) is normally less abundant but more prone to self-aggregate, and is thought to cause Alzheimer’s disease (AD). Much knowledge about AD-pathogenesis comes from the study of rodents made to model aspects of the disease by expressing AD-relevant human transgenes, like human amyloid precursor protein (APP) containing mutations that drive up Aβ production or increase the Aβ42/40 ratio and thereby causes AD. Yet, when it comes to the normal expression of Aβ42 in rodent brains, surprisingly little is known. Here we characterize the expression of Aβ42 throughout the brain of normal, outbred Wistar rats, including animals from 3-18 months of age. We find that intracellular Aβ42 (iAβ42) is present in neurons located throughout the brain at all ages of normal Wistar rats, but that the levels vary greatly between brain regions. In cortex, we observe the highest levels of iAβ42 in neurons that are part of layer II of the entorhinal cortex (EC), along with neurons in the hippocampus, closely followed by neurons in the somatosensory cortex. Among subcortical structures, we observe the highest levels iAβ42 in the locus coeruleus. In order to explore whether the striking presence of iAβ42 in rat EC also holds true in human subject free of neurological disease, we examined EC of six such cases ranging from ages 20-88 years. In all six cases, we find that iAβ42 is present in EC layer II-neurons.Our findings support two conclusions about iAβ42. First, iAβ42 is present in neurons of wild-type Wistar rats and is restricted to the same structures where iAβ accumulates, and Aβ-plaques form, in a much used AD model based on Wistar rats (the McGill-R-Thy1-APP rat model). The difference between wild-type Wistar rats and these AD model rats, with respect to Aβ42, is therefore a quantitative one rather that a qualitative one. This indicates that the McGill rat model in fact models the underlying wild-type neuronal population-specific vulnerability to Aβ42-accumulation. Second, because the McGill rat model closely mimics the human AD-associated spatiotemporal sequence of amyloid plaque deposition, this model may offer a useful representation of the pre-plaque neuronal accumulation of iAβ42. Our findings in human cases are in line with prior findings, and substantiate the notion that neurons in layer II of EC are vulnerable to accumulation of iAβ42.
The maternal microbiome promotes placental development in mice
Authors: Pronovost Geoffrey N. , Telang Sahil S. , Chen Angela S. , Coley Elena J.L. , Vuong Helen E. , Williams Drake W. , Yu Kristie B. , Rendon Tomiko K. , Paramo Jorge , Kim Reuben H. , Hsiao Elaine Y. 
Published: February 2023

AbstractThe maternal microbiome is an important regulator of gestational health, but how it impacts the placenta as the interface between mother and fetus remains unexplored. Here we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate angiogenesis-related tube formation by endothelial cells and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
How important are concurrent vehicle control groups in (sub)chronic non-human primate toxicity studies conducted in pharmaceutical development? An opportunity to reduce animal numbers
Authors: Mecklenburg Lars , Lenz Sarah , Hempel Georg 
Published: February 2023

AbstractSafety assessment of human pharmaceuticals demands extensive animal experiments before a compound can be tested in patients or released on the market. Such experiments typically include concurrent vehicle control groups. Reconsidering the need for concurrent controls could support the strive to reduce the use of animals for scientific purposes. We reviewed reports from 20 (sub)chronic toxicity studies that were conducted in non-human primates (NHP) to characterize hazards of novel human pharmaceuticals. Firstly, we determined the toxicological endpoints that were identified to characterize the hazard. Secondly, we evaluated if the hazard could have been identified without reference to the concurrent controls. Thirdly, we employed an alternative statistical method to test for any significant change related to dose level or time. We found that toxicologically relevant hazards were identifiable without reference to concurrent controls, because individual measurements could be compared with pre-dosing values or because individual measurements could be compared to historical reference data. Effects that could not be evaluated without reference to concurrent controls were clinical observations and organ weights for which appropriate historical reference data was not available, or immune responses that could not be compared to pre-dosing measurements because their magnitude would change over time. Our investigation indicates that concurrent control groups in (sub)chronic NHP toxicity studies are of limited relevance for reaching the study objective. Under certain conditions, regulatory (sub)chronic NHP toxicity studies represent a good starting point to implement virtual control groups rather than concurrent control groups in nonclinical safety testing.
Intraspecific proteomic profiling and potential biological activities of the honey bee hemolymph
Authors: Elfar Salma A. , Bahgat Iman M. , Shebl Mohamed A. , Lihoreau Mathieu , Tawfik Mohamed M. 
Published: February 2023

AbstractPollinator declines have raised major concerns for the maintenance of biodiversity and food security, calling for a better understanding of environmental factors that affect their health. Here we used hemolymph analysis, a cheap, simple, yet powerful approach, to monitor the health state of Western honey beesApis mellifera. We evaluated the intraspecific proteomic variations and the biological activities of hemolymph of bees collected from four Egyptian localities characterized by different food diversities and abundances. Lowest protein concentrations and the weakest bioactivities were recorded in hemolymph of bees artificially fed sucrose solution and no pollen. By contrast, highest protein concentrations and activities were recorded in bees that had the opportunity to feed on various natural resources. While future studies should expand comparisons to honey bee populations exposed to more different diets, our results strongly suggest hemolymph samples can be used as reliable indicators of bee nutrition and health.
Copper drives prion protein phase separation and modulates aggregation
Authors: do Amaral Mariana Juliani , Passos Aline Ribeiro , Mohapatra Satabdee , da Silva Taiana Sousa Lopes , Carvalho Renato Sampaio , Almeida Marcius da Silva , de Sá Pinheiro Anderson , Wegmann Susanne , Cordeiro Yraima 
Published: February 2023

AbstractPrion diseases are characterized by prion protein (PrP) transmissible aggregation and toxicity in the brain. The physiological function of PrP seems related to sequestering and internalization of redox-active Cu2+. It is unclear whether Cu2+contributes to PrP aggregation, recently shown to be mediated by PrP condensation. We investigated the role of Cu2+and oxidation in PrP condensation and aggregation using multiple biophysical and biochemical methods. We find that Cu2+promotes PrP condensation at the cell surface andin vitrothrough co-partitioning. Molecularly, Cu2+inhibited PrP β-structure and hydrophobic residues exposure. Oxidation, induced by H2O2, triggered liquid-to-solid transition of PrP:Cu2+condensates and promoted amyloid-like PrP aggregation. In cells, overexpression of PrPCinitially protected against Cu2+cytotoxicity but led to PrPCaggregation upon extended copper exposure. Our data suggest that PrP condensates function as a buffer for copper that prevent copper toxicity but can transition into PrP aggregation at prolonged oxidative stress.
A method for rapid nanobody screening with no bias of the library diversity
Authors: Tao Zhiqing , Zhao Xiaoling , Wang Huan , Zhang Juan , Jiang Guosheng , Yu Bin , Chen Yihao , Zhu Mingjun , Long Junli , Yin Lei , Zhang Xu , Liu Maili , He Lichun 
Published: February 2023

AbstractNanobody refers to the variable domain of heavy-chain-only antibodies. The distinctive advantages of nanobodies including small size, feasible expression inEscherichia coli(E. coli), and superior stability make them promising tools for applications in scientific research and therapies. So far, the screening and expression of nanobodies are mainly following similar methods used for conventional antibodies, suffering from amplification-caused losses of the diversity of libraries and requirements of subcloning of interests into the expression vector. Here, based on the unique properties of nanobodies, we developed an integrated method to screen and express nanobodies simultaneously with no bias of the library diversity. The library of nanobodies was cloned and secretively expressed into the culture medium. Target specifical binding nanobodies were isolated through 1-3 rounds of dilution and regrown steps in a way following the Poisson distribution to ensure no positive clones were dismissed, while the population of positive clones increased by more than 10 folds upon each round of dilution. Ultimately, 5 nanobodies against the death domain receptor 5 (DR5) and 5 nanobodies against thePyrococcus furiosus(Pfu) DNA polymerase were produced directly out of their immunized libraries, respectively. Additionally, our approach allowed nanobody screening even without any specialized instruments/devices, demonstrating general applicability in the routine production of monoclonal nanobodies for diverse biomedical applications.
Evidence for an aquatic origin of influenza virus and the orderArticulavirales
Authors: Petrone Mary E. , Parry Rhys , Mifsud Jonathon C. O. , Van Brussel Kate , Vorhees Ian , Richards Zoe T. , Holmes Edward C. 
Published: February 2023

ABSTRACTThe emergence of novel disease-causing viruses in mammals is part of the long evolutionary history of viruses. Tracing these evolutionary histories contextualises virus spill over events and may help to elucidate how and why they occur. We used a combination of total RNA sequencing and transcriptome data mining to extend the diversity and evolutionary history of the orderArticulavirales, which includes the influenza viruses. From this, we identified the first instance ofArticulaviralesin the Cnidaria (including corals), constituting a novel and divergent family that we tentatively named theCnidenomoviridae. This may be the basal group within theArticulavirales. We also extended the known evolutionary history of the influenza virus lineage by identifying a highly divergent, sturgeon-associated influenza virus. This suggests that fish were among the first hosts of influenza viruses. Finally, we substantially expanded the known diversity of quaranjaviruses and proposed that this genus be reclassified as a family (theQuaranjaviridae). We find evidence that vertebrate infectingQuaranjaviridaemay have initially evolved in crustaceans before spilling into terrestrial Chelicerata (i.e., ticks). Together, our findings indicate that theArticulaviraleshas evolved over at least 600 million years, first emerging in aquatic animals. Importantly, the evolution of this order was not shaped by strict virus-host codivergence, but rather by multiple aquatic-terrestrial transitions and substantial host jumps, some of which are still observable today.