bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study
Authors: Flisiak Robert , Zarębska-Michaluk Dorota , Berkan-Kawińska Aleksandra , Tudrujek-Zdunek Magdalena , Rogalska Magdalena , Piekarska Anna , Kozielewicz Dorota , Kłos Krzysztof , Rorat Marta , Bolewska Beata , Szymanek-Pasternak Anna , Mazur Włodzimierz , Lorenc Beata , Podlasin Regina , Sikorska Katarzyna , Oczko-Grzesik Barbara , Iwaszkiewicz Cezary , Szetela Bartosz , Pabjan Paweł , Pawłowska Małgorzata , Tomasiewicz Krzysztof , Polańska Joanna , Jaroszewicz Jerzy 
Published: November 2020

AbstractBackgroundRemdesivir (RDV) is the only antiviral drug registered currently for treatment of COVID-19 after a few clinical trials with controversial results. The purpose of this study was to evaluate the effectiveness and safety of RDV in patients with COVID-19 in real world settings.MethodsPatients were selected from 1496 individuals included in the SARSTer national database; 122 of them received therapy with RDV and 211 were treated with lopinavir/ritonavir (LPV/r)-based therapy. The primary end-point of effectiveness was clinical improvement in the ordinal 8-point scale, which was defined as a 2-point decrease from baseline to 7, 14, 21 and 28 days of hospitalization. The secondary end-points of effectiveness included: death rate, rate of no clinical improvement within 28 days of hospitalization in the ordinal scale, rate of the need for constant oxygen therapy, duration of oxygen therapy, rate of the need for mechanical ventilation, total hospitalization time, and rate of positive RT PCR for SARS-CoV-2 after 30 days.FindingsSignificantly higher rates of clinical improvement, by 15% and 10% respectively, were observed after RDV treatment compared to LPV/r at days 21 and 28. The difference between regimens increased with worsening of oxygen saturation (SpO2) and depending on the baseline score from the ordinal scale. Statistically significant differences supporting RDV were also noted regarding the rate of no clinical improvement within 28 days of hospitalization and hospitalization duration in patients with baseline SpO2 ≤90%. In the logistic regression model only the administration of remdesivir was independently associated with at least a 2-point improvement in the ordinal scale between baseline and day 21.InterpretationIn conclusion, data collected in this retrospective, observational, real world study supported use of remdesivir for treatment of SARS-CoV-2 infection particularly in patients with oxygen saturation ≤95%.
Glucose response to low-dose glucagon for insulin-induced mild hypoglycaemia after 12 weeks of high versus low carbohydrate diet. A pilot study
Authors: Ranjan Ajenthen G. , Schmidt Signe , Holst Jens J. , Christensen Merete B. , Nørgaard Kirsten 
Published: November 2020

AbstractObjectiveTo compare the glucose response to low-dose glucagon after high carbohydrate diet (HCD) versus low carbohydrate diet (LCD).MethodsIndividuals with insulin pump-treated type 1 diabetes went through 12 weeks of HCD (>250 g/day) and 12 weeks of LCD (<100 g/day) in random order and separated by 12 weeks. At end of each diet, mild hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus. When plasma glucose (PG) reached 3.9 mmol/L, 100 µg glucagon was given subcutaneously.ResultsFour of six participants completed both study visits while the remaining two only completed the study visit following LCD. They were 37 (28-52) years old (median (IQR)), had BMI 25.0 (24.5-25.2) kg/m2, and HbA1c 57 (55-59) mmol/mol or 7.4 (7.2-7.5) %. Daily carbohydrate intake was 95 (86-97) g during LCD and 254 (184-259) g during HCD. Compared with HCD, LCD had a significantly lower area under the PG curve from 0-120 min (521 (394-617) vs 663 (546-746) mmol/l x min, p=0.045) and insignificant lower incremental PG peak after the glucagon bolus (1.5 (0.6-3.2) vs 3.0 (2.2-4.2) mmol/L, p=0.317).ConclusionIn conclusion, the glucose response to low-dose glucagon was reduced after 12 weeks of LCD compared with HCD.
Cost-effectiveness of intensive care for hospitalized Covid-19 patients: experience from South Africa
Authors: Cleary SM , Wilkinson T , Tchuem CR Tamandjou , Docrat S , Solanki GC 
Published: November 2020

AbstractBackgroundAmidst the shortages of critical care resources in the public sector resulting from the COVID-19 pandemic, the South African Government embarked on an initiative to purchase critical bed capacity from the private sector. Within an already under-funded public health sector, it is imperative that the costs and effects of potential interventions to care are assessed and weighed against the opportunity costs of their required investment.ObjectiveTo assess the cost-effectiveness of ICU management for admitted COVID-19 patients across the public and private health sector in South Africa.MethodsUsing a Markov modelling framework and a health system perspective, the costs and health outcomes of inpatient management of severe and critical COVID-19 patients in (1) general ward and intensive care (GW+ICU) and (2) general ward only were assessed. Disability adjusted life years (DALYs) were evaluated as health outcomes, and the cost per admission from public and private sectors was determined. The models made use of four variables: mortality rates, utilisation of inpatient days for each management approach, disability weights associated to the severity of the disease, and the unit cost per general ward day and per ICU day in public and private hospitals. The unit costs were multiplied by utilisation estimates to determine the cost per admission. DALYs were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). An incremental cost-effectiveness ratio (ICER) representing the difference in costs and health outcomes of the two management strategies - was calculated and compared to a cost-effectiveness threshold to determine the value for money of ICU management.ResultsA cost per admission of ZAR 75,127 was estimated for inpatient management of severe and critical COVID-19 patients in general wards only as opposed to ZAR 103,030 in GW+ICU. DALYs were 1.48 and 1.10 in the general ward only and GW+ICU, respectively. The ratio of difference in costs and health outcomes between the two management strategies produced an ICER equal to ZAR 73 091 per DALY averted, a value above the cost-effectiveness threshold of ZAR 38 465.ConclusionsThis study indicated that purchasing additional ICU capacity from the private sector may not be a cost-effective use of limited health resources. The ‘real time’, rapid, pragmatic, and transparent nature of this analysis demonstrates a potential approach for further evidence generation for decision making relating to the COVID-19 pandemic response and South Africa’s wider priority setting agenda.
Association of COVID-19 RT-qPCR test false-negative rate with patient age, sex and time since diagnosis
Authors: Levine-Tiefenbrun Matan , Yelin Idan , Uriel Hedva , Kuint Jacob , Schreiber Licita , Herzel Esma , Katz Rachel , Ben-Tov Amir , Patalon Tal , Chodick Gabriel , Kishony Roy 
Published: November 2020

AbstractBackgroundRoutine testing for SARS-CoV-2 in the community is essential for guiding key epidemiological decisions from the quarantine of individual patients to enrolling regional and national preventive measures. Yet, the primary testing tool, the RT-qPCR based testing, is notoriously known for its low sensitivity, i.e. high risk of missed detection of carriers. Quantifying the false-negative rate (FNR) of the RT-qPCR test at the community settings and its dependence on patient demographic and disease progression is therefore key in designing and refining strategies for disease spread prevention.MethodsAnalyzing 843,917 test results of 521,696 patients, we identified false-negative (FN) and true-positive (TP) results as negative and positive results preceded by a COVID-19 diagnosis and followed by a later positive test. Regression analyses were used to determine associations of false-negative results with time of sampling after diagnosis, patient demographics and viral loads based on RT-qPCR Ct values of the next positive tests.FindingsThe overall FNR was 22.8%, which is consistent with previous studies. Yet, this rate was much lower at the first 5 days following diagnosis (10.7%) and only increased in later dates. Furthermore, the FNR was strongly associated with demographics, with odds ratio of 1.74 (95% CI: 1.58-1.90) for women over men and 1.36 (95% CI: 1.34-1.39) for 10 years younger patients. Finally, FNR was associated with viral loads (p-value 0.0005), with a difference of 1.50 (95% CI: 0.70-2.30) between the average Ct of the N gene in a positive test following a false-negative compared to a positive test following a true-positive.InterpretationOur results show that in the first few days following diagnosis, when results are critical for quarantine decisions, RT-qPCR testing is more reliable than previously reported. Yet the reliability of the test result is reduced in later days as well as for women and younger patients, where the viral loads are typically lower.FundingThis research was supported by the ISRAEL SCIENCE FOUNDATION (grant No. 3633/19) within the KillCorona – Curbing Coronavirus Research Program.
Prognostic factors of chest CT findings for ICU admission and mortality in patients with COVID-19 pneumonia
Authors: Kazemi Mohammad Ali , Ghanaati Hossein , Moradi Behnaz , Chavoshi Mohammadreza , Hashemi Hassan , Hemmati Samira , Rouzrokh Pouria , Gity Masoumeh , Ahmadinejad Zahra , Abdollahi Hamed 
Published: November 2020

AbstractBackgroundStudies have shown that CT could be valuable for prognostic issues in COVID-19Objectiveto investigate the prognostic factors of early chest CT findings in COVID-19 patients.Materials and MethodsThis retrospective study included 91 patients (34 women, and 57 men) of RT-PCR positive COVID-19 from 3 hospitals in Iran between February 25, 2020, to march 15, 2020. Patients were divided into two groups as good prognosis, discharged from the hospital and alive without symptoms (48 patients), and poor prognosis, died or needed ICU care (43 patients). The first CT images of both groups that were obtained during the first 8 days of the disease presentation were evaluated considering the pattern, distribution, and underlying disease. The total CT-score was calculated for each patient. Univariate and multivariate analysis with IBM SPSS Statistics v.26 was used to find the prognostic factors.ResultsThere was a significant correlation between poor prognosis and older ages, dyspnea, presence of comorbidities, especially cardiovascular and pulmonary. Considering CT features, peripheral and diffuse distribution, anterior and paracardiac involvement, crazy paving pattern, and pleural effusion were correlated with poor prognosis. There was a correlation between total CT-score and prognosis and an 11.5 score was suggested as a cut-off with 67.4% sensitivity and 68.7% specificity in differentiation of poor prognosis patients (patients who needed ICU admission or died. Multivariate analysis revealed that a model consisting of age, male gender, underlying comorbidity, diffused lesions, total CT-score, and dyspnea would predict the prognosis better.ConclusionTotal chest CT-score and chest CT features can be used as prognostic factors in COVID-19 patients. A multidisciplinary approach would be more accurate in predicting the prognosis.
A gain and dynamic range independent index to quantify spillover spread to aid panel design in flow cytometry
Authors: Bhowmick Debajit , van Diepen Frank , Pfauth Anita , Tissier Renaud , Ratliff Michelle 
Published: November 2020

AbstractIn conventional flowcytometry one detector (primary) is dedicated for one fluorochrome. However, photons usually end up in other detectors too (fluorescence spillover). ‘Compensation’ is a process that corrects the spillover signal from all detectors except the primary detector. Post ‘compensation’, the photon counting error of spillover signals become evident as spreading of the data. The spreading induced by spillover impairs the ability to resolve stained cell population from the unstained one, potentially reducing or completely losing cell populations. For successful multi-color panel design, it is important to know the expected spillover to maximize the data resolution. The Spillover Spreading Matrix (SSM) can be used to estimate the spread, but the outcome is dependent on detector sensitivity. Simply, the same single stained sample produces different spillover spread values when detector(s) sensitivity is altered. Many researchers mistakenly use this artifact to “reduce” the spread by decreasing detector sensitivity. This can result in diminished capacity to resolve dimly expressing cell populations. Here, we introduce SQI (Spread Quantification Index), that can quantify the spillover spread independent of detector sensitivity and independent of dynamic range. This allows users to compare spillover spread between instruments having different types of detectors, which is not possible using SSM.
Standard Procedures for Native CZE-MS of Proteins and Protein Complexes up to 800 kDa
Authors: Jooss Kevin , McGee John P. , Melani Rafael D. , Kelleher Neil L. 
Published: November 2020

AbstractNative mass spectrometry (nMS) is a rapidly growing method for the characterization of large proteins and protein complexes, preserving “native” non-covalent inter- and intramolecular interactions. Direct infusion of purified analytes into a mass spectrometer represents the standard approach for conducting nMS experiments. Alternatively, CZE can be performed under native conditions, providing high separation performance while consuming trace amounts of sample material. Here, we provide standard operating procedures for acquiring high quality data using CZE in native mode coupled online to various Orbitrap mass spectrometers via a commercial sheathless interface, covering a wide range of analytes from 30 – 800 kDa. Using a standard protein mix, the influence of various CZE method parameters were evaluated, such as BGE/conductive liquid composition and separation voltage. Additionally, a universal approach for the optimization of fragmentation settings in the context of protein subunit and metalloenzyme characterization is discussed in detail for model analytes. A short section is dedicated to troubleshooting of the nCZE-MS setup. This study is aimed to help normalize nCZE-MS practices to enhance the CE community and provide a resource for production of reproducible and high-quality data.
Engineered Red Blood Cells Carrying PCSK9 Inhibitors Persistently Lower LDL and Prevent Obesity
Authors: Deshycka Rhogerry , Sudaryo Valentino , Huang Nai-Jia , Xie Yushu , Smeding Liyan Y. , Choi Moon Kyung , Ploegh Hidde L. , Lodish Harvey F. , Pishesha Novalia 
Published: November 2020

AbstractLow plasma levels of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) are associated with decreased low-density lipoprotein (LDL) cholesterol and a reduced risk of cardiovascular disease. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of LDL receptors (LDLR), very low-density lipoprotein receptors (VLDLR), apolipoprotein E receptor 2 (ApoER2), and lipoprotein receptor–related protein 1 (LRP1) and accelerates their degradation, thus acting as a key regulator of lipid metabolism. Antibody and RNAi - based PCSK9 inhibitor treatments lower cholesterol and prevent cardiovascular incidents in patients, but their high cost hampers market penetration. We sought to develop a safe, long-term and one-time solution to treat hyperlipidemia. We created a cDNA encoding a chimeric protein in which the extracellular N-terminus of glycophorin A was fused to the LDLR EGFA domain and introduced this gene into mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). Following transplantation into irradiated mice, the animals produced red blood cells (RBCs) with the EGFA domain (EGFA-GPA RBCs) displayed on their surface. These animals showed significantly reduced plasma PCSK9 (66.5% decrease) and reduced LDL levels (40% decrease) for as long as 12 months post-transplantation. Furthermore, the EGFA-GPA mice remained lean for life and maintained normal body weight under high-fat diet. Hematopoietic stem cell gene therapy can generate red blood cells expressing an EGFA - glycophorin A chimeric protein as a practical and long-term strategy for treating chronic hyperlipidemia and obesity.
Music for cells? A systematic review of studies investigating the effects of audible sound played through speaker-based systems to cell cultures
Authors: Kwak Dongho , Combriat Thomas , Wang Chencheng , Scholz Hanne , Danielsen Anne , Jensenius Alexander Refsum 
Published: November 2020

AbstractThere have been several studies investigating whether musical sound can be used as cell stimuli in recent years. We systematically searched publications to get an overview of studies that have used audible sound played through speaker-based systems to induce mechanical perturbation in cell cultures. A total of 12 studies were identified. We focused on the experimental setups, the sound materials used as stimuli, and the outcomes. The stimuli were categorized into simple and complex sounds. The effects were reported as enhanced cell migration, proliferation, colony formation, and differentiation ability. However, there are significant differences in methodologies and cell type-specific outcomes, which made it difficult to find a systematic pattern in the results. We suggest that future experiments should consider using: 1) a more controlled acoustic environment), 2) standardized sound and noise measurement methods, and 3) a more comprehensive range of controlled sound stimuli.
Short-Beaked Echidna (Tachyglossus aculeatus) Home Range at Fowlers Gap Arid Zone Research Station, NSW
Authors: Badgery Georgia J. , Lawes Jasmin C. , Leggett Keith E.A. 
Published: November 2020

ABSTRACTEchidnas(Tachyglossus aculeatus)are found Australian-wide and appear to be remarkably well-adapted to arid zones, yet, nearly all echidna research has been conducted in temperate, tropical and alpine zones. This study investigated the home range and movement of echidnas in western New South Wales. Radio telemetry tracking was used to locate the echidnas daily during the study period (March-May 2019 and August 2019); the home range was 1.47± 1.21 km2. This is over twice the reported home range of temperate environments (>0.65 km2) suggesting that echidnas exhibit larger home ranges in arid zones. This study provides insight into the movement and home range of echidnas in arid zones, revealing that desert echidnas have large home ranges, dependent on the availability of resources.
Experimental evolution of adaptive divergence under varying degrees of gene flow
Authors: Tusso Sergio , Nieuwenhuis Bart P.S. , Weissensteiner Bernadette , Immler Simone , Wolf Jochen B.W. 
Published: November 2020

ABSTRACTAdaptive divergence is the key evolutionary process generating biodiversity by means of natural selection. Yet, the conditions under which it can arise in the presence of gene flow remain contentious. To address this question, we subjected 132 sexually reproducing fission yeast populations sourced from two independent genetic backgrounds to disruptive ecological selection and manipulated the level of migration between environments. Contrary to theoretical expectations, adaptive divergence was most pronounced when migration was either absent (‘allopatry’) or maximal (‘sympatry’), but was much reduced at intermediate rates (‘parapatry’, ‘local mating’). This effect was apparent across central life history components (survival, asexual growth, and mating), but differed in magnitude between ancestral genetic backgrounds. The evolution of some fitness components was constrained by pervasive negative correlations (trade-off between asexual growth and mating), while others changed direction under the influence of migration (e.g. survival and mating). In allopatry, adaptive divergence was mainly conferred by standing genetic variation and resulted in ecological specialization. In sympatry, divergence was mainly mediated by novel mutations enriched in a subset of genes and was characterized by the repeated emergence of two strategies: an ecological generalist and an asexual growth specialist. Multiple loci showed consistent evidence for antagonistic pleiotropy across migration treatments and provide a conceptual link between adaptation and divergence. This evolve-and-resequence experiment demonstrates that rapid ecological differentiation can arise even under high rates of gene flow. It further highlights that adaptive trajectories are governed by complex interactions of gene flow, ancestral variation and genetic correlations.
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity
Authors: Alles Sascha R.A. , Odem Max A. , Lu Van B. , Cassidy Ryan M. , Smith Peter A. 
Published: November 2020

AbstractBrain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of ‘silent’ neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]ifluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.