bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis of myeloid cells in HPV+tonsillar cancer
Authors: Jimenez David Gomez , Altunbulakli Can , Swoboda Sabine , Sobti Aastha , Askmyr David , Ali Ashfaq , Greiff Lennart , Lindstedt Malin 
Published: October 2022

ABSTRACTThe incidence of Human Papillomavirus positive (HPV+) tonsillar cancer has been sharply rising during the last two decades. Myeloid cells represent an appropriate therapeutic target due to their ability to orchestrate antigen-specific immunity within the tonsil, the availability of viral antigens, and the proximity of the tumor and the underlying lymphoid tissue. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+tonsillar cancer. Our analysis unveiled the existence of four dendritic cell lineages, two macrophage polarization processes, and their sequential maturation profiles. We observed an expansion of the myeloid compartment in HPV+tonsillar cancer, accompanied by interferon-induced cellular responses both in DCs and monocyte-macrophages. Within the DC lineages, we describe a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s, in HPV+lesions. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC profile. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which gave raise to inflammatory-activated, and chemokine-producing macrophages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1, activated DCs and macrophages in patient survival using signature scoring. The current study contributes towards the understanding of myeloid ontogeny and dynamics in human papilloma driven tonsillar cancer, and details myeloid biomarkers that can be used to predict therapy effects and assess patient prognosis.
Patterns of siderophore production and utilization at Station ALOHA from the surface to mesopelagic waters
Authors: Bundy Randelle M. , Manck Lauren E. , Repeta Daniel J. , Church Matthew J. , Hawco Nicholas J. , Boiteau Rene M. , Park Jiwoon , DeLong Edward F. , Saito Mak A. 
Published: October 2022

AbstractThe North Pacific subtropical gyre is a globally important contributor to carbon uptake and an oligotrophic ecosystem primarily limited by nitrogen. The microbial community is also seasonally exposed to low iron due to biological consumption and seasonally variable iron delivery. In this study, we examined changes in iron uptake rates, dissolved siderophore concentrations, and siderophore biosynthesis at Station ALOHA across time (2013-2016) and depth (surface to 500 m) to observe changes in iron acquisition and internal cycling by the microbial community. The genetic potential for siderophore biosynthesis was widespread throughout the upper water column, and biosynthetic gene clusters peaked in spring and summer along with siderophore concentrations, suggesting changes in nutrient delivery, primary production, and carbon export impact iron acquisition over the seasonal cycle. Dissolved iron turnover times, calculated from iron-amended experiments conducted using surface (15 m) and mesopelagic (300 m) waters, ranged from 9-252 days. The shortest average turnover times at both depths were associated with inorganic iron additions (14±9 days) and the longest with iron bound to strong siderophores (148±225 days). Uptake rates of siderophore-bound iron were faster in the mesopelagic waters than in the surface, leading to high Fe:C uptake ratios of heterotrophic bacteria in the upper mesopelagic. The rapid cycling and high demand for Fe at 300 m suggests differences in microbial metabolism and iron acquisition in the mesopelagic compared to surface waters. Together, changes in siderophore production and consumption over the seasonal cycle suggest organic carbon availability impacts iron cycling at Station ALOHA.Scientific Significance StatementMicrobial community production in the subtropical oligotrophic North Pacific is limited by macronutrients such as nitrogen. However, dissolved iron is another important micronutrient that has seasonal inputs from dust and passing eddies, keeping the availability of iron low and episodic. Little attention has been paid to the microbial strategies for dealing with low iron to support primary production in the oligotrophic ocean, or how limited iron availability impacts the processing of sinking particulate organic carbon in this region. In this study, we explore iron cycling including siderophore production and uptake by the microbial community throughout the water column at Station ALOHA to examine how the microbial community adapts and responds to changing iron and carbon availability on seasonal timescales.
Predicting Pacific cod spawning habitat in a changing climate
Authors: Bigman Jennifer S. , Laurel Benjamin J. , Kearney Kelly , Hermann Albert J. , Cheng Wei , Holsman Kirstin K. , Rogers Lauren A. 
Published: October 2022

AbstractWarming temperatures elicit shifts in habitat use and geographic distributions of fishes, with uneven effects across life stages. Spawners and embryos are particularly sensitive to environmental conditions, with direct impacts of temperature on spawning habitat, as well as indirect connections between their population dynamics and fisheries effort, productivity, and management. Here, we ask how changing environmental conditions and thermal sensitivities of developing embryos confer spatiotemporal variability of thermally-suitable spawning habitat for Pacific cod in the eastern Bering Sea. Specifically, we use bottom temperature values from regionally downscaled global climate models coupled with an experimentally-derived relationship between hatch success and temperature to predict how the extent, mean latitude, and consistency of suitable spawning habitat has changed in the past and may change into the future. We then validate our predictions of suitable spawning habitat with distributions of adults and larvae and examine whether thermal habitat availability relates to recruitment success into the adult cod into the population. We find that the extent and mean latitude of suitable spawning habitat increase over time, particularly if no climate change mitigation occurs in the future. Hotspots of suitable spawning habitat are consistent across shorter time periods but do shift across the Bering Sea shelf by the end of the century. Finally, we find no correlation between the availability of suitable spawning habitat and annual estimates of recruitment. Collectively, our results suggest that as temperatures warm, the availability of suitable spawning habitat will increase and expand spatially and, thus, is not likely to limit recruitment. This work highlights the importance of coupling experimental data with climate models to identify the complex and mechanistic dynamics among temperature, life histories, and ecology, and offers a pathway for examining life stage-specific changes in habitat use and distribution with continued climate change.
Mechanical Stimuli such as Shear Stress and Piezo1 Stimulation Generate Red Blood Cell Extracellular Vesicles
Authors: Sangha Gurneet S. , Weber Callie M. , Sapp Ryan M. , Setua Saini , Thangaraju Kiruphagaran , Pettebone Morgan , Doctor Allan , Buehler Paul W. , Clyne Alisa M. 
Published: October 2022

AbstractCirculating red blood cell extracellular vesicles (RBC-EVs) are a promising biomarker for vascular health. However, generating, isolating, and characterizing physiologically relevant RBC-EVs with sufficient yield and purity for biological studies is non-trivial. Here, we present and rigorously characterize an in vitro model to mimic RBC-EV production during shear stress via mechanosensitive piezo1 ion channel stimulation. We optimize our RBC-EV isolation protocol to minimize hemolysis, maximize RBC-EV yield and purity, and improve the ease of EV characterization. RBC-EV purity was measured by quantifying protein (e.g., particles/μg), large particle (e.g., protein aggregates), and platelet EV contamination. This study compared RBC-EV isolation performance using membrane-based affinity (e.g., exoEasy), ultrafiltration (e.g., Amicon Ultra-15), and ultracentrifugation, with and without size exclusion chromatography purification. We found that treating 6% hematocrit with 10 μM piezo1-agonist yoda1 for 30 minutes and isolating RBC-EVs using ultracentrifugation minimized RBC hemolysis and maximized RBC-EV yield (~1012 particles/mL) and purity, provided the most consistent RBC-EV preparations, and improved ease of RBC-EV characterization. Our pressure myography experiments suggest that co-isolated protein contaminants, but not piezo1 RBC-EVs, induce rapid mouse carotid artery vasodilation. These results underscore the importance of characterizing EV purity for biological experiments. The standardized methods outlined here enable mechanistic studies of how RBC-EVs generated in physiological flow affect vascular response.
Factors affecting trust in clinical trials conduct: Views of stakeholders from a qualitative study in Ghana
Authors: Chatio Samuel Tamti , Ganle John Kuumuori , Adongo Philip Baba , Beisel Ulrike 
Published: October 2022

AbstractIntroductionGlobally, there are signs of declining public trust in science, especially in biomedical research. In Ghana, there are equally signs of public distrust in the conduct of biomedical research in Ghana. Typical examples are the unsuccessful conduct of the Ebola vaccine trial and the initial refusal of parents to allow their children to receive the recently piloted malaria vaccine in Ghana. Therefore, this study explored stakeholders’ views on factors affecting trust in clinical trials conduct in Ghana.MethodsThis was a cross-sectional exploratory study using qualitative research approach. Forty-eight in-depth interviews and Key informant interviews were conducted with stakeholders. Purposive sampling technique was used to select participants. All the interviews were recorded, transcribed and coded into main and sub-themes using QSR Nvivo 12 software to aid thematic analysis.ResultsOverall, participants saw the need for the conduct of clinical trials in Ghana because clinical trial studies enable scientists to come out with effective medicines for the management of diseases. Pre-implementation factors such as inadequate stakeholder engagement, rumours and negative influence affected trust. Implementation factors such as perceived risks about clinical trials medicines, apprehensions on drawing and use of blood samples, poor informed consent administration and perceived no illness all negatively affected trust in clinical trials conduct.ConclusionTrust is a fundamental factor affecting a successful conduct of clinical trials. Thus, there is need for collective efforts by all stakeholders including research institutions and clinical trial regulatory bodies to take the issue of trust in clinical trials conduct seriously.
Capturing clinical progression in multisystemic genetic ataxias: lessons from a prospective study of 884 patients with autosomal recessive or early-onset ataxia
Authors: Traschütz Andreas , Adarmes-Gomez Astrid D. , Anheim Mathieu , Baets Jonathan , Brais Bernard , Gagnon Cynthia , Gburek-Augustat Janina , Doss Sarah , Hanagasi Hasmet A. , Kamm Christoph , Klivenyi Peter , Klockgether Thomas , Klopstock Thomas , Minnerop Martina , Münchau Alexander , Renaud Mathilde , Santorelli Filippo M. , Schöls Ludger , Thieme Andreas , Vielhaber Stefan , van de Warrenburg Bart P. , Zanni Ginevra , Hilgers Ralf-Dieter ,   PREPARE consortium, Synofzik Matthis 
Published: October 2022

AbstractObjectiveThe Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.MethodsSubitem-level correlation- and distribution-based analysis of 1637 SARA assessments in 884 patients with autosomal-recessive/early-onset ataxia (370 with 2-8 longitudinal assessments), complemented by linear mixed-effects modeling to estimate progression and sample sizes.ResultsWhile SARA subitem responsiveness varied between ataxia severities,gait/stanceshowed a robust granular linear scaling across the broadest range (SARA<25). Responsiveness was diminished by incomplete sub-scale use at intermediate or upper levels, non-transitions (“static periods”), and fluctuating decreases/increases. All subitems -exceptnose-finger-showed moderate-to-strong correlations to activities of daily living, indicating that metric properties -not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes, e.g., SYNE1-ataxia: 0.55 points/year, AOA2: 1.14, POLG-ataxia: 1.56; but no change in others (ARSACS, COQ8A-ataxia). While sensitivity to change was optimal in mild ataxia (SARA≤10), it substantially deteriorated in advanced ataxia (SARA>25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitemsfinger-chaseandnose-fingerreduces sample sizes by 20-25%.InterpretationThis study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design.
Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review
Authors: Rashid Asrar , Al-Obeida Feras , Krishnan Hari , Benakatti Govind , Hafez Wael , Brierley Joe , Hanisch Benjamin , Khilnani Praveen , Koutentis Christos , Brusletto Berit S , Toufiq Mohammed , Hussain Zain , Vyas Harish , Malik Zainab , Schumacher Maike , Malik Rayaz , Deshpande Shriprasad , Quraishi Nasir , Kadwa Raziya , Sarpal Amrita , Shaikh M. Guftar , Sharief Javed , Zaki Syed Ahmed , Phatak Rajesh , Deep Akash , Al-Dubai Ahmed , Hussain Amir 
Published: October 2022

AbstractSepsis remains a major global health issue in pediatric and adult populations, largely due to a lack of understanding of its complex pathophysiology. Despite its high mortality rate, there have been few advancements in sepsis-specific therapies over recent decades. The study aimed to investigate the potential benefits of a genome-wide transcriptomic approach to sepsis in pediatric and adult populations in reducing sepsis-related mortality and enhancing sepsis guidelines. The scoping review explored gene expression data pertinent to developing sepsis guidelines related to its definition, classification, disease severity, molecular biomarking, and benchmarking. A system-biology approach using transcriptomics was adopted to enhance the understanding of sepsis at the mRNA gene expression level. The study involved a search of the PubMed database for original research or systematic reviews that involved transcriptomic application in the context of clinical sepsis published over a ten-year period, from 2012-2022. Of the 14,048 studies retrieved, a full-text analysis was performed. Five main concepts emerged: case definition, classification, quantifying severity of sepsis, transcriptomic biomarkers, and benchmarking. Studies were categorized according to these five categories. The results showed evidence of a connection between the transcript and clinical sepsis, demonstrating that transcript-driven sepsis categorization is possible. Integrating transcriptomic data with clinical endpoints holds promise for more precise sepsis treatment. Although further exploration is needed, the methodology shows potential for disease modification.
Disparities in Naltrexone Prescriptions to Medicaid Enrollees During the COVID-19 Pandemic
Authors: Subervi Hemmy A. , Varghese Lysine E. , Piper Brian J. 
Published: October 2022

AbstractBackgroundThe COVID-19 pandemic strained healthcare facilities and the isolation and uncertainty associated with the pandemic compromised mental health around the world. The pandemic has also been associated with an exacerbation of the opioid crisis in the United States (US), and previous studies have reported changing trends in opioid misuse during the pandemic. Our study investigated naltrexone, a prescription drug used to treat alcohol and opioid use disorders by blocking opioid receptors to reduce cravings. We sought to investigate the changes in naltrexone prescriptions issued to Medicaid enrollees in light of the COVID-19 pandemic.MethodsThe total number of naltrexone, generic and brand name, prescriptions across the US were obtained from the Medicaid.gov database, expressed as prescriptions per state corrected for the number of enrollees, and organized into two time periods - the pre-pandemic period from January 2019 to December 2019 and the pandemic period from January 2020 to March 2021. Statistical analyses included a paired t-test, a heat map to depict state level variation, and waterfall figures. Procedures were approved by the IRB of Geisinger.ResultsThere were increases in total naltrexone prescriptions throughout the time frame studied, but a decrease in prescriptions per 100,000 Medicaid enrollees. A paired t-test revealed a significant decrease in naltrexone prescriptions during the pandemic period. There was a 398-fold difference between the highest and lowest states in 2019 Quarter 1 and 424-fold in 2021 Quarter 1. Percent change calculations indicated South Dakota (+141%) and Oregon (+172%) showed a significant increase in total naltrexone prescriptions from pre-pandemic to post-pandemic from the national mean (−23.57%+5.60%).ConclusionsThe results of this study were significant and indicated a relationship between the COVID-19 pandemic and declining naltrexone prescription rates. Naltrexone prescriptions per 100,000 enrollees decreased in most states during the pandemic and fell by over 32% nationally from 2019 to 2021 despite a slight increase in total prescription numbers and an increase in Medicaid enrollees. These data suggest wide variation in access to substance use disorder treatment during the pandemic. Further research with privately insured patients may be beneficial.
Gyroscope Vector Magnitude: A proposed measure for accurately measuring angular velocities
Authors: Chen Howard , Schall Mark , Fethke Nathan 
Published: October 2022

AbstractHigh movement velocities are among the primary risk factors for work-related musculoskeletal disorders (MSDs). Ergonomists have commonly used two methods to calculate angular movement velocities of the upper arms using inertial measurement units (accelerometers and gyroscopes). Generalized velocity is the speed of movement traveled on the unit sphere per unit time. Inclination velocity is the derivative of the postural inclination angle relative to gravity with respect to time. Neither method captures the full extent of upper arm angular velocity. We propose a new method, the gyroscope vector magnitude (GVM), and demonstrate how GVM captures angular velocities around all motion axes and more accurately represents the true angular velocities of the upper arm. We use optical motion capture data to demonstrate that the previous methods for calculating angular velocities capture 89% and 77% relative to our proposed method. We propose GVM as the standard metric for reporting angular arm velocities in future research.
COVID-19: impact of original, Gamma, Delta, and Omicron variants of SARS-CoV-2 in vaccinated and unvaccinated pregnant and postpartum women
Authors: Serra Fabiano Elisei , Rosa Elias Ribeiro , de Rossi Patricia , Vieira Francisco Rossana Pulcineli , Rodrigues Agatha Sacramento 
Published: October 2022

ABSTRACTIntroductionThis study compares the clinical characteristics and disease progression of vaccinated and unvaccinated pregnant and postpartum women positive for the original, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Brazilian epidemiological data.MethodsData of pregnant or postpartum patients with coronavirus disease 2019 (COVID-19) SARS-CoV-2 confirmed using polymerase chain reaction from February 2020 to July 2022 were extracted from a Brazilian national database. The patients were divided based on vaccination status and viral variant (original, Gamma, Delta, and Omicron). The patients’ demographic data, clinical characteristics, comorbidities, signs, symptoms, and outcomes were retrospectively compared.ResultsData from 10,003 pregnant and 2,361 postpartum women were extracted from the database. Among unvaccinated patients, postpartum women were more likely to be admitted to the intensive care unit (ICU). These patients were more likely to require invasive ventilation when infected with the original, Gamma, and Omicron variants and were more likely to die when infected with the original and Gamma variants. Patients who were vaccinated had reduced adverse outcomes including ICU admission, requirement for invasive ventilation, and death.ConclusionPostpartum women were more likely to develop severe COVID-19 that required ICU admission or invasive ventilatory support or led to death, among all variants, especially when the patients were unvaccinated. Therefore, the risk of severe COVID-19 should not be underestimated after delivery. Vaccinated patients had a lower risk of severe outcomes. Vaccination should be a top priority in pregnant and postpartum patients.WHAT IS ALREADY KNOWN ON THIS TOPICThe obstetric population has a higher risk of adverse outcomes due to coronavirus disease 2019 (COVID-19). Few studies have compared the outcomes of pregnant and postpartum patients or vaccinated and unvaccinated patients; however, no studies have separately investigated the effects of each viral variant.WHAT THIS STUDY ADDSPostpartum women are more likely to have adverse outcomes, including the requirements for intensive care and invasive ventilation and death, compared with pregnant women. Vaccinated women had fewer adverse outcomes. The viral variants did not significantly affect the outcomes of these patients.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICYThe risks of COVID-19 infection should not be underestimated in postpartum women. Postpartum women infected with COVID-19, especially those who are not vaccinated, should be monitored carefully. Vaccination should be a top priority in pregnant and postpartum women.
Multi-omic Analysis of Primary Human Kidney Tissues Identifies Medulla-Specific Gene Expression Patterns
Authors: Haug Stefan , Muthusamy Selvaraj , Li Yong , Köttgen Anna , Akilesh Shreeram 
Published: October 2022

AbstractThe renal medulla is a specialized region of the kidney with important homeostatic functions. It has also been implicated in genetic and developmental disorders and ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla’s baseline gene expression and epigenomic signatures have not been well described in the adult human kidney. Here we generate and analyze gene expression (RNA-seq), chromatin accessibility (ATAC-seq) and chromatin conformation (Hi-C) data from adult human kidney cortex and medulla. Using data from our carefully annotated specimens, we assign samples in the larger public GTEx database to cortex and medulla, thereby identifying several misassignments and extracting meaningful medullary gene expression signatures. Using integrated analysis of gene expression, chromatin accessibility and conformation profiles, we reveal insights into medulla development and function. Our datasets will also provide a valuable resource for researchers in the GWAS community for functional annotation of genetic variants.