bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoscopic findings in patients with persistent dyspepsia in a tertiary care hospital of south Punjab
Authors: Din Chaudhary Farooq Mohyud , Gul Muhammad Asif , Hameed Rizwan , Zaidi Yasir Abbas , Kanju Shehryar , Ilyas Muhammad , Zubair Muhammad , Umar Qasim , Altaf Syeda Manal , Tameez-ud-din Ahsan 
Published: December 2021

ABSTRACTBackgroundOne of the most common clinical problem encountered by physicians in clinical practice is dyspepsia. This symptom has great impact on quality of life of patients. There are numerous causes of dyspepsia, organic as well as functional. Endoscopy is the diagnostic test of choice in these patients.AimThe aim of our study was to see the endoscopic findings in patients with persistent dyspepsia.MethodsRetrospective analysis of data of patients who underwent Esophagogastroduodenoscopy (EGD) for persistent dyspepsia was collected and evaluated.ResultsThere were 495 patients in our study, 244 females and 251 males, with a mean age of 41 years. Almost half of the patients belonged to 21-40 years age group. The most common endoscopic finding in patients with persistent dyspepsia was gastritis (n=219, 44.2%), followed by normal endoscopy (n= 94, 19%), incompetent lower esophageal sphincter (n=67, 13.5%), gastric malignancy (n=48, 9.7%). Ulcer disease was found in just 15 patients (3%).ConclusionMost common endoscopic finding in patients with persistent dyspepsia was gastritis followed by normal endoscopy.
The HUNT Study: a population-based cohort for genetic research
Authors: Brumpton Ben M. , Graham Sarah , Surakka Ida , Skogholt Anne Heidi , Løset Mari , Fritsche Lars G. , Wolford Brooke , Zhou Wei , Nielsen Jonas Bille , Holmen Oddgeir L. , Gabrielsen Maiken E. , Thomas Laurent , Bhatta Laxmi , Rasheed Humaira , Zhang He , Kang Hyun Min , Hornsby Whitney , Moksnes Marta R. , Coward Eivind , Melbye Mads , Giskeødegård Guro F. , Fenstad Jørn , Krokstad Steinar , Næss Marit , Langhammer Arnulf , Boehnke Michael , Abecasis Gonçalo R. , Åsvold Bjørn Olav , Hveem Kristian , Willer Cristen J. 
Published: December 2021

SummaryThe Trøndelag Health Study (HUNT) is a population-based cohort of ∼229,000 individuals recruited in four waves beginning in 1984 in Trøndelag County, Norway. ∼88,000 of these individuals have available genetic data from array genotyping. HUNT participants were recruited during 4 community-based recruitment waves and provided information on health-related behaviors, self-reported diagnoses, family history of disease, and underwent physical examinations. Linkage via the Norwegian personal identification number integrates digitized health care information from doctor visits and national health registries including death, cancer and prescription registries. Genome-wide association studies of HUNT participants have provided insights into the mechanism of cardiovascular, metabolic, osteoporotic and liver-related diseases, among others. Unique features of this cohort that facilitate research include nearly 40 years of longitudinal follow-up in a motivated and well-educated population, family data, comprehensive phenotyping, and broad availability of DNA, RNA, urine, fecal, plasma, and serum samples.
Continuous genomic diversification of long polynucleotide fragments drives the emergence of new SARS-CoV-2 variants of concern
Authors: Murugadoss Karthik , Niesen Michiel J.M. , Raghunathan Bharathwaj , Lenehan Patrick J. , Ghosh Pritha , Feener Tyler , Anand Praveen , Simsek Safak , Suratekar Rohit , Hughes Travis K. , Soundararajan Venky 
Published: December 2021

AbstractHighly transmissible or immuno-evasive SARS-CoV-2 variants have intermittently emerged and outcompeted previously circulating strains, resulting in repeated COVID-19 surges, reinfections, and breakthrough infections in vaccinated individuals. With over 5 million SARS-CoV-2 genomes sequenced globally over the last 2 years, there is unprecedented data to decipher how competitive viral evolution results in the emergence of fitter SARS-CoV-2 variants. Much attention has been directed to studying how specific mutations in the Spike protein impact its binding to the ACE2 receptor or viral neutralization by antibodies, but there is limited knowledge of a genomic signature that is shared primarily by the sequential dominant variants. Here we introduce a methodology to quantify the genome-wide distinctiveness of polynucleotide fragments of various lengths (3-to 240-mers) that constitute SARS-CoV-2 sequences (freely available at https://academia.nferx.com/GENI). Compared to standard phylogenetic distance metrics and overall mutational load, the quantification of distinctive 9-mer polynucleotides provides a higher resolution of separation between VOCs (Reference = 89, IQR: 65-108; Alpha = 166, IQR: 150-182; Beta 130, IQR: 113-147; Gamma = 165, IQR: 152-180; Delta = 234, IQR: 216-253; and Omicron = 294, IQR: 287-315). Omicron’s exceptionally high genomic distinctiveness may confer a competitive advantage over both prior VOCs (including Delta) and the recently emerged and highly mutated B.1.640.2 (IHU) lineage. Expanding on this analysis, evaluation of genomic distinctiveness weighted by intra-lineage 9-mer conservation for 1,363 lineages annotated in GISAID highlights that genomic distinctiveness has increased over time (R2=0.37) and that VOCs score significantly higher than contemporary non-VOC lineages, with Omicron among the most distinctive lineages observed till date. This study demonstrates the value of characterizing new SARS-CoV-2 variants by their genome-wide polynucleotide distinctiveness and emphasizes the need to go beyond a narrow set of mutations at known functionally or antigenically salient sites on the Spike protein. The consistently higher distinctiveness of each emerging VOC compared to prior VOCs suggests that real-time monitoring of genomic distinctiveness would aid in more rapid assessment of viral fitness.
Influenza A H1N1–mediated pre-existing immunity to SARS-CoV-2 predicts COVID-19 outbreak dynamics
Authors: Almazán Nerea Martín , Rahbar Afsar , Carlsson Marcus , Hoffman Tove , Kolstad Linda , Rönnberg Bengt , Pantalone Mattia Russel , Fuchs Ilona Lewensohn , Nauclér Anna , Ohlin Mats , Sacharczuk Mariusz , Religa Piotr , Amér Stefan , Molnár Christian , Lundkvist Åke , Susrud Andres , Sörensen Birger , Söderberg-Nauclér Cecilia 
Published: December 2021

AbstractBackgroundSusceptibility to SARS-CoV-2 infections is highly variable, ranging from asymptomatic and mild infections in most, to deadly outcome in few. This individual difference in susceptibility and outcome could be mediated by a cross protective pre-immunity, but the nature of this pre-immunity has remained elusive.MethodsAntibody epitope sequence similarities and cross-reactive T cell peptides were searched for between SARS-CoV-2 and other pathogens. We established an ELISA test, a Luminex Multiplex bead array assay and a T cell assay to test for presence of identified peptide specific immunity in blood from SARS-CoV-2 positive and negative individuals. Mathematical modelling tested if SARS-CoV-2 outbreak dynamics could be predicted.FindingsWe found that peptide specific antibodies induced by influenza A H1N1 (flu) strains cross react with the most critical receptor binding motif of the SARS-CoV-2 spike protein that interacts with the ACE2 receptor. About 55–73% of COVID-19 negative blood donors in Stockholm had detectable antibodies to this peptide, NGVEGF, in the early pre-vaccination phase of the pandemic, and seasonal flu vaccination trended to enhance SARS-CoV-2 antibody and T cell immunity to this peptide. Twelve identified flu/SARS-CoV-2 cross-reactive T cell peptides could mediate protection against SARS-CoV-2 in 40–71% of individuals, depending on their HLA type. Mathematical modelling taking pre-immunity into account could fully predict pre-omicron SARS-CoV-2 outbreaks.InterpretationThe presence of a specific cross-immunity between Influenza A H1N1 strains and SARS-CoV-2 provides mechanistic explanations to the epidemiological observations that influenza vaccination protects people against SARS-CoV-2 infection.
Mitigating isolation: The use of rapid antigen testing to reduce the impact of self-isolation periods
Authors: Bays Declan , Whiteley Timothy , Pindar Matt , Taylor Johnathon , Walker Brodie , Williams Hannah , Finnie Thomas J. R. , Gent Nick 
Published: December 2021

AbstractIsolating, either enforced or self-guided, is a well-recognised and used technique in the limitation and reduction of disease spread. This usually balances the societal harm of disease transmission against the individual harm of being isolated and is typically limited to a very small number of individuals. With the widespread transmission of SARS-CoV-2 and requirements to self-isolate when symptomatic or having tested positive, the number of people affected has grown very large causing noticeable individual cost, and disruption to the provision of essential services. With widespread access to reliable rapid antigen tests (also known as LFD or LFTs), in this paper we examine strategies to utilise this testing technology to limit the individual harm whist maintaining the protective effect of isolation. We extend this work to examine how isolation may be improved and mitigate the release of infective individuals into the population caused by fixed time-periods.
Extending upon: What effect might border screening have on preventing importation of COVID-19 compared with other infections? – Considering the additional effect of post-arrival isolation
Authors: Bays Declan , Bennett Emma , Finnie Thomas 
Published: December 2021

AbstractWe recently described a simple model through which we assessed what effect subjecting travellers to a single on-arrival test might have on reducing risk of importing disease cases during simulated outbreaks of COVID-19, Influenza, SARS, and Ebola. We build upon this work to allow for the additional requirement that inbound travellers also undergo a period of self-isolation upon arrival, where upon completion the traveller is again tested for signs of infection prior to admission across the border. Prior results indicated that a single on-arrival test has the potential to detect 9% of travellers infected with COVID-19, compared to 35%, 10% and 3% for travellers infected with influenza, SARS, and Ebola respectively. Our extended model shows that testing administered after a 2-day isolation period may be able to detect up to 41%, 97%, 44% and 15% of COVID-19, Influenza, SARS, and Ebola infected travellers respectively. Longer self-isolation periods increase detection rates further, with an 8-day self-isolation period suggesting detection rates of up to 94%, 100%, 98% and 62% for travellers infected with COVID-19, Influenza, SARS, and Ebola respectively. These results therefore suggest that testing arrivals after an enforced period of self-isolation may present a reasonable method of protecting against case importation during international outbreaks.
Unsuspected clonal spread of Methicillin-resistant Staphylococcus aureus causing bloodstream infections in hospitalized adults detected using whole genome sequencing
Authors: Talbot Brooke M. , Jacko Natasia F. , Petit Robert A. , Pegues David A. , Shumaker Margot J. , Read Timothy D. , David Michael Z. 
Published: December 2021

AbstractBackgroundThough detection of transmission clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections is a priority for infection control personnel in hospitals, the transmission dynamics of MRSA among hospitalized patients with bloodstream infections (BSIs) has not been thoroughly studied. Whole genome sequencing (WGS) of MRSA isolates for surveillance is valuable for detecting outbreaks in hospitals, but the bioinformatic approaches used are diverse and difficult to compare.MethodsWe combined short-read WGS with genotypic, phenotypic, and epidemiological characteristics of 106 MRSA BSI isolates collected for routine microbiological diagnosis from inpatients in two hospitals over 12 months. Clinical data and hospitalization history were abstracted from electronic medical records. We compared three genome sequence alignment strategies to assess similarity in cluster ascertainment. We conducted logistic regression to measure the probability of predicting prior hospital overlap between clustered patient isolates by the genetic distance of their isolates.ResultsWhile the three alignment approaches detected similar results, they showed some variation. A pangenome-based alignment method was most consistent across MRSA clonal complexes. We identified nine unique clusters of closely-related BSI isolates. Most BSI were healthcare-associated and community-onset. Our logistic model showed that with 13 single nucleotide polymorphisms the likelihood that any two patients in a cluster overlapped in a hospital was 50 percent.ConclusionsMultiple clusters of closely related MRSA isolates can be identified using WGS among strains cultured from BSI in two hospitals. Genomic clustering of these infections suggest that transmission resulted from a mix of community spread and healthcare exposures long before BSI diagnosis.SummaryMultiple clusters of closely related MRSA bloodstream infections were identified using WGS in two hospitals using three bioinformatic workflows. Genomic epidemiology suggests that transmission resulted from a mix of community spread and healthcare exposures long before symptom onset.
Personalized Feeding Infusion Rate of Nutrition to Improve Glycemic Variability Control in Critical Care Patients
Authors: Abohtyra Rammah 
Published: December 2021

AbstractControl-based algorithms in the intensive care unit (ICU) patients have been developed to deliver a sufficient amount of insulin, but optimizing the rate of feeding of nutrition in ICU patients to improve glycemic variability control has not been done yet. Continuous feeding is commonly used for nutrition in critically ill patients who cannot be fed orally to maintain a normal blood sugar concentration, but optimizing its rate, for these individuals, is needed to avoid the adverse outcomes caused by medications such as insulin. This paper develops a control-based algorithm combines a predictive control algorithm with a revised nonlinear compartmental model used in the ICU to design personalized feeding function rates to improve patient glycemic variability. Our control algorithm is robust and acts very quickly to avoid medical intervention effects.
Identifying Mitral Valve Prolapse at Risk for Ventricular Arrhythmias and Myocardial Fibrosis from 12-lead Electrocardiograms using Deep Learning
Authors: Tison Geoffrey H. , Abreau Sean , Lim Lisa , Crudo Valentina , Barrios Joshua , Nguyen Thuy , Hu Gene , Dixit Shalini , Nah Gregory , Lee Yoojin , Delling Francesca N. 
Published: December 2021

ABSTRACTBackgroundMitral valve prolapse (MVP) is a common valvulopathy, with a subset of MVP patients developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) represents a marker of arrhythmic risk that is associated with myocardial fibrosis and increased mortality in MVP. We hypothesize that an ECG-based machine-learning model can identify MVP with ComVE and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging.MethodsA deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients evaluated at the University of California San Francisco (UCSF) between 2012 and 2020. A separate CNN was also trained to detect late gadolinium enhancement (LGE) using 87 ECGs from MVP patients with contrast CMR.Results: The prevalence of ComVE was 160/569 or 28% (20 patients or 3% had cardiac arrest or sudden cardiac death). The area under the curve (AUC) of the CNN to detect ComVE was 0.81 (95% CI, 0.78-0.84). AUC remained high even after excluding patients with moderate-severe mitral regurgitation (MR) [0.80 (95% CI, 0.77-0.83)], or with bileaflet MVP [0.81 (95% CI, 0.76-0.85)]. The top ECG segments able to discriminate ComVE vs no ComVE were related to ventricular depolarization and repolarization (early-mid ST and QRS fromV1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 21 (24%) of 87 patients with available CMR. The AUC for detection of LGE was 0.75 (95% CI, 0.68-0.82).ConclusionsStandard 12-lead ECGs analyzed with machine learning can detect MVP at risk for ventricular arrhythmias and fibrosis and can identify novel ECG correlates of arrhythmic risk regardless of leaflet involvement or mitral regurgitation severity. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.
Early Treatment with Fluvoxamine Among Patients with COVID-19: A Cost-Consequence Model
Authors: Mills Fergal P. , Reis Gilmar , Thorlund Kristian , Forrest Jamie I. , Guo Christina M. , Boulware David R , Mills Edward J. ,   for the TOGETHER Investigators
Published: December 2021

SummaryBackgroundThree randomized trials have been conducted indicating a clinical benefit of early treatment with fluvoxamine versus placebo for adults with symptomatic COVID-19. We assessed the cost-consequences associated with the use of this early treatment in outpatient populations.MethodsUsing results from the three completed trials of fluvoxamine vs. placebo for the treatment of COVID-19, we performed a meta-analysis. We conducted a cost-consequence analysis using a decision-model to assess the health system benefits of the avoidance of progression to severe COVID-19. Outcomes of relevance to resource planning decisions in the US and elsewhere, including costs and days of hospitalization avoided, were reported. We constructed a decision-analytic model in the form of a decision tree to evaluate two treatment strategies for high-risk patients with confirmed, symptomatic COVID-19, from the perspective of a third-party payer:(1) treatment with a 10-day course of fluvoxamine (100mg twice daily); (2) current standard-of-care; (3) molnupiravir 5-day course. We used a time horizon of 28 days.ResultsAdministration of fluvoxamine to symptomatic outpatients with COVID-19 at high-risk of developing progression to severe COVID-19 complications is substantially cost-saving in the US, in the amount of $232 per eligible patient, and saves an average of 0.15 hospital days per patient treated is likely to be similarly beneficial in other settings. Fluvoxamine is cost saving in locations where total hospital costs are >$738. Molnupiravir had an additional cost to the healthcare system of $404 per patient treated.ConclusionsFluvoxamine is cost-saving for COVID-19 outpatient therapy.FundingFastGrants and Rainwater Charitable Foundation
In vitro evolution predicts emerging CoV-2 mutations with high affinity for ACE2 and cross-species binding
Authors: Bate Neil , Savva Christos G , Moody Peter CE , Brown Edward A , Ball Jonathan K , Schwabe John WR , Sale Julian E , Brindle Nicholas PJ 
Published: December 2021

AbstractEmerging SARS CoV-2 variants are creating major challenges in the ongoing Covid-19 pandemic. Predicting CoV-2 mutations that increase transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines and prioritising viral monitoring and containment. Using in vitro evolution, we identify a double mutation in CoV-2 receptor binding domain (RBD) that increases affinity for ACE2 almost 20-fold. We determine the mutant:ACE2 structure to reveal the binding mechanism and show the main affinity driver, Q498H, boosts binding of other RBD variants. We find this mutation incompatible with the common N501Y mutation, but N501Y variants can acquire Q498R to access a similar bonding network and affinity gain. We show Q498H, and Q498R plus N501Y, enable variants to bind rat ACE2 with high affinity. These mutations are now emerging in CoV-2 variants, such as the Omicron variant, where they would be expected to drive increased human-to-human and cross-species transmission.
Pathological slow-wave activity and impaired working memory binding in post-traumatic amnesia
Authors: Mallas Emma-Jane , Gorgoraptis Nikos , Dautricourt Sophie , Pertzov Yoni , Scott Gregory , Sharp David J. 
Published: December 2021

AbstractThe mechanism by which information is bound together in working memory is a central question for cognitive neuroscience. This binding is transiently disrupted during periods of post-traumatic amnesia following significant head injuries. The reason for this impairment is unclear but may be due to electrophysiological changes produced by head impacts. These are common and include pathological low frequency activity, which is associated with poorer neurological outcomes and may disrupt cortical communication. Here, we investigate associative memory binding during post-traumatic amnesia and test the hypothesis that misbinding is caused by a disruption in cortical communication produced by the pathological slowing of brain activity. Thirty acute moderate-severe traumatic brain injury patients (mean time since injury = 10 days) and 26 healthy controls were tested with a precision working memory paradigm that required the association of object and location information. A novel entropy ratio measure was calculated from behavioural performance. This provided a continuous measure of the degree of misbinding and the influence of distracting information. Resting state EEG was used to assess the electrophysiological effects of traumatic brain injury. Patients in post-traumatic amnesia showed abnormalities in working memory function and made significantly more misbinding errors than patients who were not in post-traumatic amnesia and controls. Patients showed a higher entropy ratio in the distribution of spatial responses, indicating that working memory recall was abnormally biased by the locations of non-target items suggesting a specific impairment of object and location binding. Slow wave activity was increased following traumatic brain injury. Increases in the delta-alpha ratio indicative of an increase in low frequency power specifically correlated with binding impairment in working memory. In contrast, although connectivity was increased in the theta band and decreased in the alpha band after traumatic brain injury, this did not correlate with working memory impairment. Working memory and electrophysiological abnormalities both normalised at six-month follow-up, in keeping with a transient increase in slow-wave activity causing post-traumatic amnesia that impaired working memory function. These results show that patients in post-traumatic amnesia show high rates of working memory misbinding that are associated with a pathological shift towards lower frequency oscillations.
Genomic surveillance reveals the emergence of SARS-CoV-2 Lineage A from Islamabad Pakistan
Authors: Umair Massab , Ikram Aamer , Rehman Zaira , Haider Syed Adnan , Badar Nazish , Ammar Muhammad , Ali Qasim , Ahad Abdul , Suleman Rana , Salman Muhammad 
Published: December 2021

AbstractThe lineage A of SARS-CoV-2 has been around the world since the start of the pandemic. In Pakistan the last case of lineage A was reported in April, 2021 since then no case has been reported. In November, 2021 during routine genomic surveillance at National Institute of Health we have found 07 cases of lineage A from Islamabad, Pakistan. The study reports two novel deletions in the spike glycoprotein. One 09 amino acid deletion (68-76 a.a) is found in the S1 subunit while another 10 amino acid deletion (679-688 a.a) observed at the junction of S1/S2 referred as furin cleavage site. The removal of furin cleavage site may result in impaired virus replication thus decreasing its pathogenesis. The actual impact of these two deletions on the virus replication and disease dynamics needs to be studied in detail. Moreover, the enhanced genomic surveillance will be required to track the spread of this lineage in other parts of the country.