bluuebunny/crossref_metadata_2025_split huggingface dataset:
The usefulness of a quantitative olfactory test for the detection of COVID-19
Authors: Lessa Marcos A , Cotta-Pereira Stella M , Ferreira Frederico A , Castiñeiras Therezinha Marta P P , Galliez Rafael M , Faffe Débora S , Leitão Isabela de C , Mariani Diana , Nascimento Erica R , Lessa Flávia S , Succi Isabela Brasil , Pedreira Carlos A 
Published: January 2021

AbstractBackgroundDuring the COVID-19 pandemic, olfactory dysfunction (anosmia or hyposmia) has been reported by many patients and recognized as a prevalent and early symptom of infection. This finding has been associated with viral-induced olfactory neuron dysfunction rather than the nasal congestion typically found in cold- or flu-like states. In literature, the prevalence of anosmia varies from 15% to 85%, and the studies, in general, were based on the subjective evaluation of patients’ self-reports of loss of smell (yes or no question). In the present study, we quantitatively evaluated olfactory dysfunction and the prevalence of fever in symptomatic patients suspected of having COVID-19 using a scratch-and-sniff olfactory test and infrared temperature testing with RT-PCR as the gold-standard comparator method to diagnose COVID-19 infection.MethodsOutpatients had their forehead temperature checked with an infrared non-contact thermometer (temperature guns). After that, they received two olfactory smell identification test (SIT) cards (u-Smell-it™; CT, USA) that each had 5 scent windows and were asked to scratch with a pencil and sniff each of the 10 small circles containing the microencapsulated fragrances and mark the best option on a response card. Nasopharyngeal swabs were then collected for Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to determine if the patients were positive or negative for COVID-19 infection. We considered the number of ‘hits’ (correct answers) ≤ 5 as positive for loss of smell (LOS) in the olfactory test; ≥ 6 hits was considered negative for LOS (i.e. normal olfactory function). All data were analyzed using Excel and Matlab software.ResultsIn the present study, 165 patients were eligible for the olfactory test and nasopharyngeal swab collection RT-PCR. Five patients were excluded because of inconclusive PCR results (n=2) and missing data (n=3). A total of 160 patients completed all the protocols. The RT-PCR positivity rate for COVID-19 was 27.5% (n=44), and PCR+ patients scored significantly worse in the olfactory test (5.5±3.5) compared to RT-PCR-patients (8.2±1.8, p<0.001). 0/44 PCR+ patients presented with a fever (≥37.8°C). In contrast an olfactory SIT had a specificity of 94.8% (95% CI, 89.1 – 98.1), sensitivity of 47.7% (95% CI, 32.7 – 63.3), accuracy of 0.82 (95% CI, 0.75 – 0.87), positive predictive value of 77.8% (95% CI, 59.6 – 88.8), negative predictive value of 82.7% (85% CI, 78.7 – 86.7), and odds ratio of 16.7.ConclusionOur results suggest that temperature checking failed to detect COVID-19 infection, while an olfactory test may be useful to help identify COVID-19 infection in symptomatic patients.
Prediction of Celiac Disease Severity and Associated Endocrine Morbidities through Deep Learning-based Image Analytics
Authors: Ehsan Lubaina , Khan Marium , Sali Rasoul , Catalano Alexis M. , Adorno William , Kowsari Kamran , Cheng Lin , Pramoonjago Patcharin , Raghavan Shyam , Silvester Jocelyn , DeBoer Mark , Moskaluk Christopher A. , Moore Sean R. , Brown Donald E. , Syed Sana 
Published: January 2021

AbstractObjectiveDevelop a deep learning-based methodology using the foundations of systems pathology to generate highly accurate predictive tools for complex gastrointestinal diseases, using celiac disease (CD) as a prototype.DesignTo predict the severity of CD, defined by Marsh–Oberhüber classification, we used deep learning to develop a model based on histopathologic features.ResultsThe study was based on a pediatric cohort of 124 patients identified with different classes of CD severity. The model predicted CD with an overall 88.7% accuracy with the highest for Marsh IIIc (91.0%; 95% sensitivity; 91% specificity). The model identified EECs as a defining feature of children with Marsh IIIc CD and endocrinopathies which was confirmed using immunohistochemistry.ConclusionThis deep learning image analysis platform has broad applications in disease treatment, management, and prognostication and paves the way for precision medicine.SummaryWhat is already known about this subject?–Deep Learning has the potential to generate predictive models for complex gastrointestinal diseases.What are the new findings?–Our deep learning-based model used the foundations of systems pathology to generate a highly accurate predictive tool for complex gastrointestinal diseases, using a celiac disease (CD) pediatric cohort as a prototype.–The model predicated CD severity with high accuracy and identified enteroendocrine cells as a defining feature of children with severe CD and endocrinopathies.How might it impact on clinical practice in the foreseeable future?–Assessment of histopathological markers at the time of diagnosis that can predict risk of severity or complications can have broad applications in disease treatment, management, and prognostication and pave the way for precision medicine.
Genomic insights into early SARS-CoV-2 strains isolated in Reunion Island
Authors: Wilkinson David A , Lebarbenchon Camille , Atyame Célestine , Hafsia Sarah , Jaffar-Bandjee Marie-Christine , Yemadje-Menudier Luce , Tanaka Sébastien , Meilhac Olivier , Mavingui Patrick 
Published: January 2021

AbstractThe relative isolation of many island communities provides some protection from the COVID-19 pandemic, as imported cases can be limited and traced effectively. Until recently, this was true for the population of the French overseas department, Reunion Island, where only limited numbers of autochthonous cases were observed prior to August 2020. Since the report of the first case of COVID-19, contact tracing has been carried out for each new case identified in Reunion Island to identify transmission and clusters. To contribute to the public health response and understand the diffusion of SARS-Cov-2 strains in Reunion Island, we established in-house genome sequencing capability in Reunion using Oxford nanopore technology (MinION) as an inexpensive option for genomic typing of SARS-CoV-2 lineages on the island, and cross-validated typing results between viral isolation methods and different sequencing technologies. The results of our work during the early phase of the epidemics are presented herein.Article Summary LineThe COVID-19 pandemic has had an unprecedented impact on the global community. Here we provide epidemiological and genomic details of the early stages of the pandemic on Reunion Island.
A Reproducible Protocol to Assess Arrhythmia Vulnerability in Silico: Pacing at the End of the Effective Refractory Period
Authors: Azzolin Luca , Schuler Steffen , Loewe Axel , Dössel Olaf 
Published: January 2021

AbstractIn both clinical and computational studies, different pacing protocols are used to induce arrhythmia and non-inducibility is often considered as the endpoint of treatment. The need for a standardized methodology is urgent since the choice of the protocol used to induce arrhythmia could lead to contrasting results, e.g., in assessing atrial fibrillation (AF) vulnerabilty. Therefore, we propose a novel method – pacing at the end of the effective refractory period (PEERP) – and compare it to state-of-the-art protocols such as phase singularity distribution (PSD) and rapid pacing (RP) in a computational study. All methods were tested by pacing from 227 evenly distributed endocardial points in a bi-atrial geometry. 6 different atrial models were implemented: 4 cases without specific AF-induced remodelling but with decreasing global conduction velocity and 2 persistent AF cases with an increasing amount of fibrosis resembling different substrate remodeling stages. Compared with PSD and RP, PEERP induced a larger variety of arrhythmia complexity requiring, on average, only 2.7 extra-stimuli and 3 s of simulation time to initiate reentry. Moreover, PEERP and PSD were the protocols which unveiled a larger number of areas vulnerable to sustain stable long living reentries compared to RP. Finally, PEERP can foster standardization and reproducibility, since, in contrast to the other protocols, it is a parameter-free method. Furthermore, we discuss its clinical applicability. We conclude that the choice of the inducing protocol has an influence on both initiation and maintenance of AF and we propose and provide PEERP as a reproducible method to assess arrhythmia vulnerability.
Understanding Vaccine Hesitancy: Empirical Evidence from India*
Authors: Sur Pramod Kumar 
Published: January 2021

AbstractWhy do vaccination rates remain low even in countries where long-established immunization programs exist and vaccines are provided for free? We study this paradox in the context of India, which contributes to the world’s largest pool of under-vaccinated children and about one-third of all vaccine-preventable deaths globally. Combining historical records with survey datasets, we examine the Indian government’s forced sterilization policy, a short-term aggressive family planning program implemented between 1976 and 1977. Using multiple estimation methods, including an instrumental variable (IV) and a geographic regression discontinuity design (RDD) approach, we document that the current vaccination completion rate is low in places where forced sterilization was high. We also explore the heterogeneous effects, mechanisms, and reasons for the mechanism. Finally, we examine the enduring consequence and present evidence that places more exposed to forced sterilization have an average 60 percent higher child mortality rate today. Together, these findings suggest that government policies implemented in the past can have persistent adverse impacts on demand for health-seeking behavior, even if the burden is exceedinglyhigh.
Adherence to the CONSORT statement and risk of bias assessment in Randomized Controlled Trials in rehabilitation journals: a protocol for a meta-research study
Authors: Innocenti Tiziano , Giagio Silvia , Salvioli Stefano , Feller Daniel , Minnucci Silvia , Brindisino Fabrizio , Ostelo Raymond , Chiarotto Alessandro 
Published: January 2021

ABSTRACTObjectiveThe aim of this study will be to assess the adherence to the reporting quality standards set forth in the CONSORT Statement checklist of a random sample of randomized controlled trials (RCTs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these RCTs.Methods and AnalysisA cross-sectional analysis is planned on a random sample of 200 RCTs published between 2011and 2020 in the 68 journals indexed under “rehabilitation” category in InCites Journal Citation Report.Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). RCT with parallel group design will be included. Observational or cohort studies, interim analyses, economic analyses of RCTs, RCT protocols, quasi-experimental design post-trial follow-up studies, subgroup and secondary analyses of previously reported RCTs, RCT with cross-over design, pilot feasibility RCTs, n-of-1 trials, cluster trials, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between CONSORT adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.Ethics and DisseminationSeveral studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Adherence to the PRISMA statement and risk of bias assessment in Systematic Reviews in rehabilitation journals: a protocol for a meta-research study
Authors: Innocenti Tiziano , Feller Daniel , Giagio Silvia , Salvioli Stefano , Minnucci Silvia , Brindisino Fabrizio , Chiarotto Alessandro , Ostelo Raymond 
Published: January 2021

ABSTRACTObjectiveThe aim of this study will be to assess the adherence to the reporting quality standards set forth in the PRISMA Statement checklist of a random sample of systematic reviews (SRs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these SRs.Methods and AnalysisA cross-sectional analysis is planned on a random sample of 200 SRs published between 2011and 2020 in the 68 journals indexed under “rehabilitation” category in InCites Journal Citation Report.Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). SRs (with or without meta-analysis) published between 2011 and 2020 as full-text scientific articles in the 68 rehabilitation journals will be included. Narrative reviews, mixed-methods reviews, meta-ethnography reviews, umbrella reviews, scoping reviews, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between PRISMA adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.Ethics and DisseminationSeveral studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Myelin pathology in ataxia-telangiectasia is the cell autonomous effect of ATM deficiency in oligodendrocytes
Authors: Tse Kai-Hei , Cheng Aifang , Yeung Sunny Hoi-Sang , Ng Jia-Nian , Cheng Gerald Wai-Yeung , Wang Qingyang , Zhu Beika , Cui Yong , Jiang Liwen , Kofler Julia , Herrup Karl 
Published: January 2021

ABSTRACTAtaxia-telangiectasia (A-T) is a rare genetic disease caused by mutations in the gene encoding the ATM (ataxia-telangiectasia mutated) protein. Although neuronal degeneration in the cerebellum remains the most prominent sign in A-T pathology, neuroimaging studies reveal myelin abnormalities as early comorbidities. We hypothesize that these myelin defects are the direct consequence of ATM deficiencies in the oligodendrocytes (OL) lineage. We examined samples from ten A-T brains in which the ATM mutations had been mapped by targeted genomic sequencing and fromAtm-/-mice. In healthy human cerebellum, we confirmed the presence of ATM in white matter OLs. In A-T, a significant reduction in OL density was found along with a massive astrogliosis. This white matter pathology was recapitulated inAtm-/-mice in an age- and gene dose-dependent fashion. Activated ATM was found expressed both in the nucleus and cytoplasm of OL progenitor cells (OPC) and myelinating mature OL. Its presence in the OL lineage is associated with novel OL-specific functions of the ATM protein affecting all stages of the OL life cycle. Blockage of ATM activity with KU-60019 or inducing DNA damage induced with etoposide altered the cell cycle in self-renewing OPC and triggered ectopic cell cycle re-entry in mature OLin vitro. Further, the differentiation program of OPC is highly sensitive to DNA damage either induced directly or by blocking DNA repair. As much of the impact of ATM deficiency in OL is independent of neuronal loss, our findings have important implications for the complex neurological symptoms of human A-T.HIGHLIGHTSOligodendrocytes are highly vulnerable to DNA double strand breaksATM regulates cell cycle control and differentiation of oligodendrocytesMyelin-pathology in Ataxia Telangiectasia is likely the cell-autonomous consequence of ATM deficiency in oligodendrocytes
Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection
Authors: Cheemarla Nagarjuna R. , Watkins Timothy A. , Mihaylova Valia T. , Wang Bao , Zhao Dejian , Wang Guilin , Landry Marie L. , Foxman Ellen F. 
Published: January 2021

AbstractThe interferon response is a potent antiviral defense mechanism, but its effectiveness depends on its timing relative to viral replication. Here, we report viral replication and host response kinetics in patients at the start of SARS-CoV-2 infection and explore the impact of these kinetics experimentally. In both longitudinal patient nasopharyngeal samples and airway epithelial organoids, we found that SARS-CoV-2 initially replicated exponentially with a doubling time of ∼6hr, and induced interferon stimulated genes (ISGs) with delayed timing relative to viral replication. Prior exposure to rhinovirus increased ISG levels and blocked SARS-CoV-2 replication. Conversely, inhibiting ISG induction abrogated interference by rhinovirus and enhanced SARS-CoV-2 replication rate. These results demonstrate the importance of initial interferon-mediated defenses in determining the extent to which SARS-CoV-2 can replicate at the start of infection and indicate that biological variables that alter the airway interferon response, including heterologous induction of innate immunity by other viruses, could profoundly impact SARS-CoV-2 susceptibility and transmission.
Longevity of SARS-CoV-2 immune responses in haemodialysis patients and protection against reinfection
Authors: Clarke Candice L , Prendecki Maria , Dhutia Amrita , Edwards Claire , Prout Virginia , Lightstone Liz , Parker Eleanor , Marchesin Federica , Griffith Megan , Charif Rawya , Pickard Graham , Cox Alison , McClure Myra , Tedder Richard , Randell Paul , Greathead Louise , Guckian Mary , McAdoo Stephen P. , Kelleher Peter , Willicombe Michelle 
Published: January 2021

ABSTRACTBackgroundPatients with end stage kidney disease (ESKD) receiving in-centre haemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, ICHD patients frequently develop serological evidence of infection, even with asymptomatic disease. The aim of this study is to investigate the durability and functionality of immune responses to SARS-CoV-2 infection in ICHD patients.MethodsThree hundred and fifty-six ICHD patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies. Patients who became seronegative at 6 months were investigated for SARS-CoV-2 specific T-cell responses.ResultsOne hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at Time 0, of which 127 (98.4%) also had detectable anti-RBD. At 6 months, of 111 patients tested, 71(64.0%) and 97 (87.4%) remained anti-NP and anti-RBD seropositive respectively, p<0.001. For patients who retained antibody, both anti-NP and anti-RBD levels reduced significantly after 6 months. Ten patients who were anti-NP and anti-RBD seropositive at Time 0, had no detectable antibody at 6 months; of which 8 were found to have SARS-CoV-2 antigen specific T cell responses.Independent of antibody status at 6 months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following 6 months.ConclusionsICHD patients mount durable immune responses 6 months post SARS-CoV-2 infection, with <3% of patients showing no evidence of humoral or cellular immunity. These immune responses are associated with a reduced risk of subsequent reinfection.SIGNIFICANCE STATEMENTFollowing infection with SARS-CoV-2, patients with end stage kidney disease (ESKD) frequently develop serological evidence of infection, even with asymptomatic disease. Patients with ESKD receiving in-centre haemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. What is not known is how durable the serological responses in ESKD patients are or whether evidence of prior immune responses protect patients from reinfection. In this study of 356 ICHD patients, at 6 months following the detection of SARS-CoV-2 antibodies, fewer than 3% of patients lacked evidence of either humoral or cellular immunity. Furthermore, patients with serological evidence of infection had a significantly lower risk of being diagnosed with subsequent infection or ‘reinfection’, suggesting functional immune protection.
Strategic Treatment Optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C
Authors: Cooke Graham S. , Pett Sarah , McCabe Leanne , Jones Chris , Gilson Richard , Verma Sumita , Ryder Stephen D , Collier Jane D , Barclay Stephen T. , Ala Aftab , Bhagani Sanjay , Nelson Mark , Ch’Ng Chinlye , Stone Ben , Wiselka Martin , Forton Daniel , McPherson Stuart , Halford Rachel , Nguyen Dung , Smith David , Ansari Azim , Dennis Emily , Hudson Fleur , Barnes Eleanor J , Walker Ann Sarah 
Published: January 2021

ABSTRACTBackgroundThe WHO has identified the need for a better understanding of which patients can be cured with ultrashort course hepatitis C (HCV) therapyMethods202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks’ sofosbuvir/ledipasvir/ribavirin. Primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment.ResultsAll evaluable participants achieved SVR12 overall (197/197, 100%[95%CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95%CI −3.8%,+3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91%[86%-97%] (92/101) for fixed-duration vs 48%[39%-57%] (47/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23/32)) than VUS1 (36% [25%-48%] (24/66)). Overall first-line SVR12 was 72%[65%-78%] (70/101) without ribavirin and 68%[61%-76%] (69/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3/26)) than without (38% [21%-58%] (11/29), p=0.01).ConclusionsUnsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir/ledipasvir/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly reduced resistance emergence in those failing first-line therapy.RegistrationISRCTN 37915093.FundingNational Institutes of Health Research.