bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the Role of Norovirus VP1 in Viral Infectivity and Persistence
Authors: Mills Jake , Snowden Joseph , Herod Morgan 
Published: May 2022

Human noroviruses (HNV) are a prevalent cause of gastroenteritis that contribute to >200,000 deaths each year and cost >£40 billion worldwide per annum. There is currently no approved vaccine or therapy, and a greater understanding of the virus life-cycle could help develop new approaches towards disease control. Although HNV infection is usually self-limiting, persistent infections can establish in immunocompromised people - however the underlying mechanisms are poorly understood. Our studies use the murine norovirus (MNV) model system to investigate fundamental virus biology, and several strains of MNV can also persist in the murine host. The primary receptor for MNV, CD300lf, interacts with a network of amino acids (AAs) on the protruding domain of the virus major capsid protein (VP1). We hypothesised that genetic variations leading to changes within this network of AAs could influence the VP1-CD300lf interaction and viral persistence.
Bioinformatic analysis of the VP1-receptor interface highlighted variation in just a single AA that correlates with persistent MNV strains. To confirm this AA is important for receptor interactions we conducted in vitro evolution experiments on suspension or adherent grown cells. Passage through suspension cells resulted in the selection of hydrophobic residues at this position co-incidental with a 1.5-fold increase in viral titre. In contrast, small polar residues were maintained at this position during passage on adherent cells. Furthermore, infectivity assays with infectious clones suggest that hydrophobic residues favour infection of suspension cells over adherent cells. Work is ongoing to understand the importance of this AA on viral infectivity and persistence.
Control Of Hepatitis E Virus Polyprotein Processing By Cellular Proteases
Authors: Pierce Danielle M. , Buchanan Frazer J. T. , Cox Abigail , Stonehouse Nicola J. , Herod Morgan R. 
Published: May 2022

Hepatitis E Virus (HEV) is one of the leading causes of acute viral hepatitis, with ~20 million HEV infections worldwide per annum, and mortality rates up to 25% in pregnant women. However, many aspects of the biology of the virus are poorly understood. HEV has a positive-sense single-stranded RNA genome. ORF1 encodes the non-structural polyprotein required for viral RNA replication. This polyprotein (sometimes termed pORF1) is predicted to contain seven domains based on sequence homology to related viruses and it is hypothesised that this polyprotein must undergo proteolysis to generate functional protein units. However, it is unknown if the pORF1 polyprotein undergoes full proteolysis, the potential locations of any cleavage boundaries and whether a viral or host cell protease is responsible.
We have adapted our in vitro-based proteolysis assays to investigate cleavage of HEV pORF1. In comparison to related RNA viruses, our data suggest that pORF1 has no auto-catalytic activity. Previous studies have shown that the liver-produced protease, thrombin, is essential for replication. In the presence of thrombin, we have shown that the ORF1 polyprotein undergoes specific proteolysis to produce eight distinct protein products. Combining bioinformatics with pORF1 truncations/mutagenesis, we have located the position of the pORF1 thrombin cleavage sites. Interestingly, these cleavage sites correspond to the junctions between the predicted pORF1 protein domains. Our data suggests that thrombin is an important cellular protease for controlling pORF1 proteolysis. Work is ongoing to understand the importance of each thrombin cleavage site in viral replication.
KNOWLEDGE AND AWARENESS OF OSTEOPOROSIS AMONG 144 YOUNG WOMEN AT CALMETTE HOSPITAL
Authors: Satha SUM , Putthimundul UY 
Published: May 2022

ABSTRACTObjectivesTo evaluate the level of knowledge and awareness about osteoporosis of young women at Calmette hospital.MethodsWe conveniently selected 144 women based on the selecting criteria. They were interviewed in Khmer language, face-to-face using structured-questionnaire which include demographic characteristic, lifestyle information, knowledge of osteoporosis and interest in an osteoporosis prevention.ResultsThe average age of the participants was 28.43 (±4.42) years. Self-employed represented a large proportion. The study showed that only one fourth of participants went to a higher education. Most of the participants stated that they have known about osteoporosis while friends or family was the most common source of information. Only 16.67% have known osteoporotic patient. Most of them have a moderately bone-friendly lifestyle. Their calcium source depended largely on green vegetable. The average mean score of knowledge was 9.34 (±3.08) (range from 0 to 20). However, a half of them worried about suffering of osteoporosis in their later years of life. Around two thirds wanted to undergo an osteoporosis screening test. A majority was interested in osteoporosis prevention. Social media and community outreach were recommended as sensitizing measures. The osteoporosis knowledge was only correlated significantly (P-value: 0.007) with educational level.ConclusionDespite of low level of knowledge of osteoporosis, young Cambodian women was interested in osteoporosis screening and prevention. Educational intervention, such as public awareness programs regarding a bone-friendly lifestyle and osteoporosis screening, is crucial in sensitizing the general population about osteoporosis and its complication.
Fast and Accurate Species Trees from Weighted Internode Distances
Authors: Liu Baqiao , Warnow Tandy 
Published: May 2022

AbstractSpecies tree estimation is a basic step in many biological research projects, but is complicated by the fact that gene trees can differ from the species tree due to processes such as incomplete lineage sorting (ILS), gene duplication and loss (GDL), and horizontal gene transfer (HGT), which can cause different regions within the genome to have different evolutionary histories (i.e., “gene tree heterogeneity”). One approach to estimating species trees in the presence of gene tree heterogeneity resulting from ILS operates by computing trees on each genomic region (i.e., computing “gene trees”) and then using these gene trees to define a matrix of average internode distances, where the internode distance in a tree T between two species x and y is the number of nodes in T between the leaves corresponding to x and y. Given such a matrix, a tree can then be computed using methods such as neighbor joining. Methods such as ASTRID and NJst (which use this basic approach) are provably statistically consistent, very fast (low degree polynomial time) and have had high accuracy under many conditions that makes them competitive with other popular species tree estimation methods. In this study, inspired by the very recent work of weighted ASTRAL, we present weighted ASTRID, a variant of ASTRID that takes the branch uncertainty on the gene trees into account in the internode distance. Our experimental study evaluating weighted ASTRID shows improvements in accuracy compared to the original (unweighted) ASTRID while remaining fast. Moreover, weighted ASTRID shows competitive accuracy against weighted ASTRAL, the state of the art. Thus, this study provides a new and very fast method for species tree estimation that improves upon ASTRID, has comparable accuracy with the state of the art while remaining much faster. Weighted ASTRID is available at https://github.com/RuneBlaze/internode.
Overuse in US Medicare during the COVID-19 pandemic: 2020 versus 2019
Authors: Chalmers Kelsey , Brownlee Shannon , Gopinath Valérie , Saini Vikas 
Published: May 2022

BackgroundThe COVID-19 pandemic and March 2020 shutdown in the US reduced the volume of healthcare services, but the impact on overuse has not been investigated.ObjectiveTo examine the change in overuse rates and volumes through 2020.DesignA retrospective cohort study using Medicare fee-for-service claims.SettingOutpatient and inpatient claims.ParticipantsPatients who met the criteria for one of 10 overuse measures with a claim between January 1 2019 to December 31 2020.MeasurementsOveruse volumes were reported as patients with claims meeting overuse metric criteria per 100,000 Medicare beneficiaries. Overuse rates were measured by the same overuse cohort per 100 patients meeting the denominator criteria of the metric. Rates in 2020 were compared to the same date period in 2019 using incidence rate ratios (IRRs) estimated from Poisson regressions.ResultsIn 2019, 302,379 patients had an overuse claim (14.72% of 2,053,792 patients in the cohort) versus 234,481 (13.79% of 1,699,807) in 2020. The overall cohort included 2,112,904 (61.0%) women and a mean (SD) age of 76.5 (8.1) years. There was a 52.3% decrease in overall cohort volume during the COVID-19 shutdown; 2,341,017 patients in 2020 versus 4,912,453 in 2019. There was a 72.57% decrease in patients with an overuse procedure between April 2019 (N = 11,794) and 2020 (N = 3,220) (IRR 0.27 (95% CI 0.25 to 0.3; p <0.001)), including spinal fusion/laminectomy, carotid endarterectomy, knee arthroscopy, hysterectomy and vertebroplasty.LimitationsThis study uses claim-based measures of overuse and is limited to the first ten months of the COVID-19 pandemic.ConclusionsThe shutdown period during March through May in 2020 had a drastic impact on both the overuse volume and rates for these 10 overuse metrics.
Limited induction of lung-resident memory T cell responses against SARS-CoV-2 by mRNA vaccination
Authors: Pieren Daan K.J. , Kuguel Sebastián G. , Rosado Joel , Robles Alba G. , Rey-Cano Joan , Mancebo Cristina , Esperalba Juliana , Falcó Vicenç , Buzón María J. , Genescà Meritxell 
Published: May 2022

AbstractResident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen (Ag)-specific TRMare detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. We found that the frequency of CD4+T cells secreting interferon (IFN)γ in response to S-peptides was variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses presented less frequently a TRMphenotype compared to convalescent infected individuals and polyfunctional CD107a+IFNγ+TRMwere virtually absent. Thus, a robust and broad TRMresponse established in convalescent-infected individuals may be advantageous in limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Still, mRNA vaccines might induce responses within the lung parenchyma, potentially contributing to the overall disease control.
Effects of Sensorimotor Voice Training on Event-Related Potentials to Pitch-Shifted Auditory Feedback
Authors: Patel Sona , Hebert Karen , Korzyukov Oleg , Larson Charles R. 
Published: May 2022

AbstractThe pitch perturbation technique is a validated technique that has been used for over 30 years to understand how people control their voice. This technique involves altering a person’s voice pitch in real-time while they produce a vowel (commonly, a prolonged /a/ sound). Although post-task changes in the voice have been observed in several studies (e.g., a change in mean F0 across the duration of the experiment), the potential for using the pitch perturbation technique as a training tool for voice pitch regulation and/or modification has not been explored. The present study examined changes in event related potentials (ERPs) and voice pitch in three groups of subjects due to altered voice auditory feedback following a brief, four-day training period. Participants in the opposing group were trained to change their voice F0 in the opposite direction of a pitch perturbation stimulus. Participants in the following group were trained to change their voice F0 in the same direction as the pitch perturbation stimulus. Participants in the non-varying group did not voluntarily change their pitch, but instead were asked to hold their voice constant when they heard pitch perturbations. Results showed that all three types of training affected the ERPs (N1 peak latency, P2 peak latency, and P2 peak amplitude) and the response latency and magnitude of the voice pitch shift response in the baseline, “hold your voice pitch steady” task (an indicator of voice pitch regulation). These results demonstrate that participation in pitch-shifted auditory feedback tasks even for brief periods of time can modulate the automatic tendency to compensate for alterations in voice pitch feedback and has therapeutic potential.
Airborne Pathogen Detection in Fine Aerosol Exhaled Breath Condensates
Authors: Henderson John , Mantso Theodora , Ali Saqib , Groß Rüdiger , Müller Janis A. , Wilkinson Amie , Shah Kavit , Usher Louise , Auld Beth , Nelson Andrew , Cheung William , Namdeo Anil , Combrinck Madeleine , Hackney Phil , Turgul Volkan , Jahaj Edison , Athanasiou Nikolaos , Nikolouzakis Taxiarchis , Almeida Pedro J. , Rokka Chrysa , Queiroz Daniel C. , Wright Edward , Zafiropoulos Alexandros , Kale Izzet , Smith Darren , Kofteridis Diamantis P. , Tsatsakis Aristides , Münch Jan , Katsaounou Paraskevi A. , Kotanidou Anastasia , Lagiou Pagona , Magiorkinis Gkikas , Aquiar Renato S , Teixeira Mauro M. , Moschos Sterghios A. 
Published: May 2022

AbstractRationaleExhaled breath condensate (EBC) promises a valuable, non-invasive, and easy to obtain clinical sample. However, it’s not currently used diagnostically due to poor reproducibility, sample contamination, and sample loss.ObjectiveWe evaluated whether a new, hand-held EBC collector (PBM-HALETM) that separates inertially impacted large droplets (LD) before condensing fine aerosols (FA) in distinct, self-sealing containers, overcomes current limitations.MethodsSampling consistency was determined in healthy volunteers by microbial culture, 16S phylogenetics, spectrophotometry, RT-PCR, and HILIC-MS. Capture of aerosolised polystyrene beads, liposomes, virus-like particles, or pseudotyped virus was analysed by nanoparticle tracking analysis, reporter expression assays, and flow cytometry. Acute symptomatic COVID-19 case tidal FA EBC viral load was quantified by RT-qPCR. Exhaled particles were counted by laser light scattering.Measurements and Main ResultsSalivary amylase-free FA EBC capture was linear (R2=0.9992; 0.25-30 min) yielding RNA (6.03 μg/mL) containing eukaryotic 18S rRNA (RT-qPCR; p<0.001) but not human GAPDH, RNase P, or beta actin mRNA;141 non-volatile metabolites included eukaryotic cell membrane components, and cuscohygrine 3 days after cocaine abuse. Culturable aerobe viability was condensation temperature-dependent. Breath fraction-specific microbiota were stable, identifying Streptococcus enrichment in a mild dry cough case. Nebulized pseudotyped virus infectivity loss <67% depended on condensation temperature, and particle charge-driven aggregation. SARS-CoV-2 RNA genomes were detected only by forced expiration FA EBC capture, in 100% of acute COVID-19 patients.ConclusionsHigh purity, distal airway FA EBC can reproducibly and robustly inform contamination-free infectious agent emission sources, and be quantitatively assayed for multiple host, microbial, and lifestyle biomarker classes.
Impact of ‘Black Race’ coefficient in eGFR on Our Community and Medical Education
Authors: Kanungo Shibani , Lorber Amy R. , Schmitt Christine , VanRiper Kaitlyn , Billian Joseph 
Published: May 2022

AbstractA critical national conversation over the use of race in estimation of glomerular filtration rate (eGFR) was stimulated by medical students at the University of Washington over the past few years. They explored, with overdue scrutiny, the ways race is portrayed and used in medical education and practice. Questions were raised about the inclusion of the multiplicative factor for Black race in eGFR calculation, with implications for differential clinical management, and the possibility of disadvantaging patients, solely based on race. Their call for investigation and action, among the rising voices of many, started a reexamination of eGFR and the numerous other areas of medicine touched by racism. As a result, national groups of physicians, scientists, specialists, and patients (including the American Society of Nephrology and National Kidney Foundation) have called for removal of race from calculation of eGFR. We scrutinized use of ‘Black race’ coefficient in eGFR calculation and consequence of its use on our local community in SW Michigan. A cross-sectional analysis of electronic health record (EHR) data from local hospital systems demonstrates the impact removal of race from eGFR calculation could have on our community. Our work may serve as a prototype for ongoing and thorough examination of questions of race in medicine. Truly eradicating racism from medicine may require continuous critical evaluation of current established norms of medical education and care. As similar issues arise in medical education, we can identify how such changes shape healthcare on a local level and integrate this knowledge into our education.Key pointsQuestionCan use of Black race in eGFR equation affects our local community?FindingsCross sectional study of a community population accessing local health care system for assessment of kidney function, found significant association between self-identified ‘Black’ population advance to CKD Stage 3 or higher upon removal of “black race” coefficient in eGFR MDRD calculation.MeaningRace use in medical practice and medical education further perpetuates systemic racism and widens health care access inequity.
The International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN Study)
Authors: Turner Michael , Beirne Cliff , Belli Antonio , Blennow Kaj , Zetterberg Henrik , Dewar Bonnie Kate , di Pietro Valentina , Gissane Conor , Heslegrave Amanda , Laverse Etienne , McEneaney Victoria , McGoldrick Adrian , Murray James , O’Halloran Patrick , Pearson Ben , Pitsiladis Yannis , Toffoli Marco , Williams Huw , McCrory Paul 
Published: May 2022

AbstractIntroduction and aimsTraumatic brain injury (TBI) is a leading cause of death and disability worldwide. Large registry studies have demonstrated a dose–response relationship between TBI and neurodegenerative disease ; however, disentangling the direct effects of TBI from ageing and/or a progressive neurodegenerative process is problematic. This study is a prospective long-term cohort study to examine a population of retired elite athletes at high risk of concussion and mTBI during their sporting careers compared to age- and sex-matched controls with no history of TBI. The aim is to determine the incidence and risk factors for neurodegenerative disease and/or age-related effects on brain health in this population.Methods and analysisA population of retired male and female elite athletes and controls aged 40-85 years, will be assessed at baseline and serial time points over 10 years during life using a multi-dimensional assessment including: Questionnaire; SCAT3/5; Neurological and physical examination; Instrumented balance assessment; Computerised neurocognitive screen; Neuropsychological assessment; Advanced MR brain neuroimaging; Visual saccades; Blood workup; Fluid biomarkers; Gut metabolomics; Salivary MicroRNA analysis; Genetic analysis; and where available Brain banking and neuropathologyEthics and disseminationEthics approval was granted by St Mary’s University SMEC as well as at the various satellite trial sites. The trial is registered with ISRCTN (BioMed Central) with ID number: 11312093. In addition to the usual dissemination process, this phenotypically well-characterised dataset will reside in a publicly accessible infrastructure of integrated databases, imaging repositories, and biosample repositories and de-identified data will be made available to collaborating researchers.
African Ancestry GWAS of Dementia in a Large Military Cohort Identifies Significant Risk Loci
Authors: Sherva Richard , Zhang Rui , Sahelijo Nathan , Jun Gyungah , Anglin Tori , Chanfreau Catherine , Cho Kelly , Fonda Jennifer R. , Gaziano J. Michael , Harrington Kelly M. , Ho Yuk-Lam , Kremen William , Litkowski Elizabeth , Lynch Julie , Neale Zoe , Roussos Panos , Marra David , Mez Jesse , Miller Mark W. , Salat David H. , Tsuang Debby , Wolf Erika , Zeng Qing , Panizzon Matthew S. , Merritt Victoria C. , Farrer Lindsay A. , Hauger Richard L. , Logue Mark W. 
Published: May 2022

AbstractWe conducted the largest genome-wide association study (GWAS) of Alzheimer’s disease and related dementia (ADRD) in individuals of African-ancestry (AFR) to date using participants from the Million Veteran Program (MVP; 4,012 ADRD cases and 18,435 controls). A proxy GWAS based on survey-reported parental dementia (n=6,641 proxy cases, 45,970 controls) was also performed. The MVP AFR ADRD GWAS and proxy GWAS results were meta-analyzed and combined with the Alzheimer’s Disease Genetics Consortium’s (ADGC) AFR AD GWAS results. The MVP meta-analysis yielded genome-wide significant associations in or near APOE, ROBO1, and RP11-340A13.2. The MVP/ADGC meta-analysis yielded additional genome-wide significant variants near known risk genes TREM2, CD2AP, and ABCA7. We examined differences in expression of the implicated genes in a cohort of AD case and control brains. This study provides insight into dementia pathophysiology in historically understudied individuals of AFR and may help to address health disparities.