bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of real-time RT-PCR based SARS-CoV-2 detection methods and its application to human derived and surface swabbed material
Authors: Tastanova Aizhan , Stoffel Corinne Isabelle , Dzung Andreas , Cheng Phil Fang , Bellini Elisa , Johansen Pål , Duda Agathe , Nobbe Stephan , Lienhard Reto , Bosshard Philipp Peter , Levesque Mitchell Paul 
Published: November 2020

AbstractReal-time reverse transcription polymerase chain reaction (RT-PCR) remains a gold standard in detection of various viral diseases. In the COVID-19 pandemic, multiple RT-PCR based tests were developed to screen for viral infection. As an emergency response to growing testing demand, we established a SARS-CoV-2 PCR diagnostics platform for which we compared different commercial and in-house RT-PCR protocols. We evaluated four commercial (CDC 2019-nCoV, Applied Biosystems™ 2019-nCoV Assay Kit v1 TF-SinglePlex, 2019-nCoV Assay Kit v2 TF-MultiPlex, and EURORealTime SARS-CoV-2), one customized (Institute Pasteur), and one in-house RT-PCR protocols with 92 SARS-CoV-2 positive and 92 SARS-CoV-2 negative samples. Furthermore, we compared economical and practical characteristics of these protocols. We also developed a highly sensitive digital droplet PCR (ddPCR) method. Finally, we conducted a local environmental study for the presence and infectivity of SARS-CoV-2 on different surfaces in a quarantined household using RT- and ddPCR methods. We found very low limits of detection (1 or 2 viral copies/μL), high sensitivities (93.6-97.8%) and specificities (98.7-100%) for the tested RT-PCR protocols. We further demonstrated the feasibility of downscaling two of the commercial protocols, which could optimize testing capacity. In the local environmental study, only one surface sample tested positive for viral RNA, but without detectable infectivity in vitro. Tested commercial and customized RT-PCR detection kits show very good and comparable sensitivity, and specificity, and the kits could be further optimized for use on SARS-CoV-2 viral samples derived from human and surface swabbed samples.
Statistical Analyses of the Public Health and Economic Performance of Nordic Countries in Response to the COVID-19 Pandemic
Authors: Gordon Daniel V. , Grafton R. Quentin , Steinshamn Stein Ivar 
Published: November 2020

AbstractAimTo compare trends and undertake statistical analyses of differences in public health performance (confirmed cases and fatalities) of Nordic countries; Denmark, Finland, Norway and Sweden, and New Zealand, in response to the COVID-19 pandemic.MethodsPer capita trends in total cases and per capita fatalities were analysed and difference-in-difference statistical tests undertaken to assess whether differences in stringency of mandated social distancing (SD) measures, testing rates and border closures explain cross-country differences.ResultsSweden is a statistical outlier, relative to its Nordic neighbours, for both per capita cases and per capita fatalities associated with COVID-19 but not in terms of the reduction in economic growth. Sweden’s public health differences, compared to its Nordic neigbours, are partially explained by differences in terms of international border closures and the level of stringency of SD measures (including testing) implemented from early March to June 2020.ConclusionsWe find that: one, early imposition of full international travel restrictions combined with high levels of government-mandated stringency of SD reduced the per capita cases and per capita fatalities associated with COVID-19 in 2020 in the selected countries and, two, in Nordic countries, less stringent government-mandated SD is not associated with higher quarterly economic growth.
Perceived mental health, wellbeing and associated factors among Nepali migrant and non-migrant workers: A qualitative study
Authors: Devkota Hridaya Raj , Bhandari Bishnu , Adhikary Pratik 
Published: November 2020

AbstractBackgroundPoor mental health and illness among the working population have serious socio-economic and public health consequences for both the individual and society/country. With a dramatic increase in work migration over the past decades, there is recent concern about the health and wellbeing of migrant workers and their accessibility to healthcare services in destination countries. This study aimed to explore the mental health and wellbeing experiences of Nepali returnee-migrants and non-migrant workers, and identify their perception on the risk factors for poor health and health service accessibility for them.MethodsThis qualitative study was conducted among Nepali migrant and non-migrant workers in February 2020. Four focus group discussions (n=25) and 15 in-depth interviews were conducted with male non-migrant and returnee migrant workers from Gulf countries and Malaysia. The discussions and interviews were audio-recorded, transcribed, translated into English and analysed thematically.ResultMigrant workers reported a higher risk of developing adverse mental health conditions than non-migrant workers. In addition, fever, upper respiratory infection, abdominal pain, ulcer, and occupational injuries were common health problems among both migrant and non-migrant workers. Other major illnesses reported by the migrant workers were heat burns and rashes, snake-bites, dengue, malaria, gallstone, kidney failure, and sexually transmitted diseases, while non-migrants reported hypertension, diabetes, and heart diseases. Adverse living and working conditions including exploitation and abuse by employers, lack of privacy and congested accommodation, language barriers, long hours’ hard physical work without breaks, and unhealthy lifestyles were the contributing factors to migrant workers’ poor mental and physical health. Both migrant and non-migrants reported poor compliance of job conditions and labor protection by their employers such as application of safety measures at work, provision of insurance and healthcare facilities that affected for their wellbeing negatively. Family problems compounded by constant financial burdens and unmet expectations were the most important factors linked with migrant workers’ poor mental health condition.ConclusionBoth migrant and non-migrant workers experienced poor mental and physical health condition largely affected by their adverse living and working conditions, unmet familial and financial needs and adherence to unhealthy life styles. It is needed to ensure the compliance of work agreement by employers and promotion of labor rights in relation to worker’s health and safety. In addition, policy interventions on raising awareness on occupational health risk and effective safety training to all migrant and non-migrant workers are recommended.
Deciphering early-warning signals of SARS-CoV-2 elimination and resurgence from limited data at multiple scales
Authors: Parag Kris V , Cowling Benjamin J , Donnelly Christl A 
Published: November 2020

AbstractInferring the transmission potential of an infectious disease during low-incidence periods following epidemic waves is crucial for preparedness. In such periods, scarce data may hinder existing inference methods, blurring early-warning signals essential for discriminating between the likelihoods of resurgence versus elimination. Advanced insight into whether elevating caseloads (requiring swift community-wide interventions) or local elimination (allowing controls to be relaxed or refocussed on case-importation) might occur, can separate decisive from ineffective policy. By generalising and fusing recent approaches, we propose a novel early-warning framework that maximises the information extracted from low-incidence data to robustly infer the chances of sustained local-transmission or elimination in real time, at any scale of investigation (assuming sufficiently good surveillance). Applying this framework, we decipher hidden disease-transmission signals in prolonged low-incidence COVID-19 data from New Zealand, Hong Kong and Victoria, Australia. We uncover how timely interventions associate with averting resurgent waves, support official elimination declarations and evidence the effectiveness of the rapid, adaptive COVID-19 responses employed in these regions.
A simple, effective enclosure with disposable coverings for inexpensive containment of aerosolized COVID viruses during tracheal intubation and extubation
Authors: Monroe Luke W. , Johnson Jack S. , Gutstein Howard B. , Lawrence John P. , Lejeune Keith , Sullivan Ryan C. , Jen Coty N. 
Published: November 2020

Structured AbstractBackgroundSARS-CoV-2 (COVID-19) is a severe respiratory virus that can be transmitted through aerosol particles produced by coughing, talking, and breathing. Medical procedures used to treat severe cases such as tracheal intubation, extubation, and tracheal suctioning produce infectious aerosol particles. This presents significant risk for viral exposure of nearby healthcare workers during and following tracheal operations. This study looks at an enclosure to limit medical personnel’s exposure to these particles.MethodsA low-cost plastic enclosure was designed to reduce aerosol spread and viral transmission during intubation and extubation procedures. The enclosure consists of clear polycarbonate for maximum visibility. Large side cutouts provide health care providers with ease of access to the patient. Aerosol particle instruments measured the aerosol containment efficacy after applying various types of plastic coverings to seal the side openings. The use of negative pressure was also tested.ResultsThe enclosure with 2 layers of plastic coverings sealing the side openings reduced total escaped particle number concentrations (diameter > 0.01 μm) by over 93% at 3 inches away from all openings. Concentration decay experiments indicated that the enclosure without active suction should be left on the patient for 15-20 minutes following a tracheal manipulation to allow sufficient time for >90% of aerosol particles to settle upon interior surfaces. This decreases to 5 minutes when 30 LPM suction is applied.ConclusionsThis enclosure is an inexpensive, easily implemented additional layer of protection that can be used to reduce the risk of SARS-CoV-2 aerosol transmission between patients and healthcare workers.
Association of antihypertensive agents with the risk of in-hospital death in patients with Covid-19
Authors: Chouchana Laurent , Beeker Nathanaël , Garcelon Nicolas , Rance Bastien , Paris Nicolas , Salamanca Elisa , Polard Elisabeth , Burgun Anita , Treluyer Jean-Marc , Neuraz Antoine 
Published: November 2020

ABSTRACTIn this retrospective multicenter cohort study, we aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19. Of 8,078 hospitalized patients for Covid-19, 3,686 (45.6%) had hypertension including 2043 (55.4%) patients exposed to a renin-angiotensin-aldosterone inhibitors (RAASi), 1624 (44.1%) to calcium channel blockers (CCB) and 1154 (37.7%) to beta-blockers. Overall in-hospital 30-day mortality was 23.1%. Compared to non-users, the risk of mortality was lower in CCB (aOR, 0.83 [0.70-0.99]) and beta-blockers users (aOR, 0.80 [0.67-0.95]), and not different in RAASi users. These findings support the continuation of antihypertensive agents in patients with Covid-19.
Fever temperatures impair hemolysis caused by strains ofEscherichia coliandStaphylococcus aureus
Authors: Palela Mihaela , Giol Elena Diana , Amzuta Andreia , Ologu Oxana G. , Stan Razvan C. 
Published: November 2020

AbstractHemolysis modulates susceptibility to bacterial infections and predicts poor sepsis outcome. Hemolytic bacteria induce upon infection a reversible fever response from the host that may aid in pathogen clearance. To delineate the role of fever temperatures on the growth and infectivity of two hemolytic bacteria that are known to evoke fever in patients via hemotoxins, we used high-sensitivity microcalorimetry to measure the evolution of heat production by fever-inducing strains ofEscherichia coliandStaphylococcus aureusunder fever conditions. We determined specific aggregation profiles at temperatures equal to or exceeding 38.5□. We confirmed these results through bacterial incubation at relevant temperatures revealing the presence or absence of hemolysis. We thus reveal an additional positive role of febrile temperatures in directly contributing to the immune response, through the abolishment of hemolysis.
PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells
Authors: Grasmann Gabriele , Planque Mélanie , Madreiter-Sokolowski Corina T. , Hrzenjak Andelko , Graier Wolfgang F. , Fendt Sarah-Maria , Olschewski Horst , Leithner Katharina 
Published: November 2020

AbstractCancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. A decrease of extracellular glucose is accompanied by enhanced mitochondrial respiration in cancer cells, which promotes the formation of potentially harmful reactive oxygen species (ROS). Here we show that a gluconeogenesis enzyme, mitochondrial phosphoenolpyruvate carboxykinase, PCK2, acts as a regulator of mitochondrial respiration and maintains the redox balance in nutrient-deprived lung cancer cells. PCK2 silencing increased the abundance and interconversion of tricarboxylic acid (TCA) cycle intermediates, augmented mitochondrial respiration and enhanced glutathione oxidation under glucose and serum starvation, in a PCK2 re-expression reversible manner. Moreover, augmenting the TCA cycle by PCK2 inhibition severely reduced colony formation. As a conclusion, PCK2 contributes to maintaining a reduced glutathione pool upon starvation besides mediating the biosynthesis of gluconeogenic/glycolytic intermediates. The study sheds light on adaptive responses in cancer cells to nutrient deprivation and identifies gluconeogenesis as starvation-induced pathway that limits respiration-induced oxidative stress.
The role of SOX9 in non-small cell lung cancer progression is histopathology-selective
Authors: Bao Jie , Närhi Katja , Teodòsio Ana , Hemmes Annabrita , Linnavirta Nora M , Mäyränpää Mikko I , Salmenkivi Kaisa , Quesne John Le , Verschuren Emmy W 
Published: November 2020

AbstractThe transcription factor SOX9 is a key regulator of multiple developmental processes, and is frequently re-expressed in non-small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histopathologies has however remained elusive. We show that SOX9 expression relates to poor outcome and invasive histopathology in human adenocarcinomas, and is absent in murine early minimally invasive and humanin situadenocarcinoma. Interestingly, despite wide SOX9 expression across advanced NSCLC histotypes, its genetic deletion in the murineKrasG12D;Lkb1-/-model selectively disrupted only the growth of papillary NSCLC, without affecting the initiation of precursor lesions or growth of mucinous or squamous tissue. Spatial tissue phenotyping indicated a requirement of SOX9 expression for the progression of surfactant protein C-expressing progenitor cells, which gave rise to papillary tumours. Intriguingly, while SOX9 expression was dispensable for squamous tissue formation, its loss in fact led to enhanced squamous tumour metastasis, which was associated with altered collagen IV deposition in the basement membrane. Our work therefore demonstrates histopathology-selective roles for SOX9 in NSCLC progression, namely a requirement for papillary adenocarcinoma progression, but opposing metastasis-suppressing function in squamous histotype tissue. This attests to a pleiotropic SOX9 function, linked to the cell of origin and microenvironmental tissue contexts.
SEPIA: Simulation-based Evaluation of Prioritization Algorithms
Authors: Almaraz Kimberly , Jang Tyler , Lewis McKenna , Ngo Titan , Song Miranda , Moshiri Niema 
Published: November 2020

AbstractBackgroundThe ability to prioritize people living with HIV by risk of future transmissions could aid public health officials in optimizing epidemiological intervention. While methods exist to perform such prioritization based on molecular data, their effectiveness and accuracy are poorly understood, and it is unclear how one can directly compare the accuracy of different methods. We introduce SEPIA (Simulation-based Evaluation of PrIoritization Algorithms), a novel simulation-based framework for determining the effectiveness of prioritization algorithms. Under several metrics of effectiveness that we propose, we utilize various properties of the simulated contact networks and transmission histories to compare existing prioritization approaches: one phylogenetic (ProACT) and one distance-based (growth of HIV-TRACE transmission clusters).ResultsUsing all metrics of effectiveness that we propose, ProACT consistently slightly outperformed the transmission cluster growth approach. However, both methods consistently performed just marginally better than random, suggesting that there is significant room for improvement in prioritization tools.ConclusionWe hope that, by providing ways to quantify the effectiveness of prioritization methods in simulation, SEPIA will aid researchers in developing novel tools for prioritizing people living with HIV by risk of future transmissions.
Micronuclei arising due to loss of KIF18A form stable micronuclear envelopes and do not promote tumorigenesis
Authors: Sepaniac Leslie A. , Martin Whitney , Dionne Louise A. , Stearns Timothy M. , Reinholdt Laura G. , Stumpff Jason 
Published: November 2020

AbstractMicronuclei, whole or fragmented chromosomes which are spatially separated from the main nucleus, are strongly associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically,Kif18amutant mice produce micronuclei due to unaligned chromosomesin vivobut do not develop spontaneous tumors, raising questions about whether all micronuclei contribute similarly to genomic instability and cancer. We report here that micronuclei inKif18amutant mice form stable nuclear envelopes. ChallengingKif18amutant mice via deletion of theTrp53gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss ofKif18ahad modest or no effect on survival ofTrp53homozygotes and heterozygotes, respectively. To further explore micronuclear envelope stability inKIF18AKO cells, we compared micronuclei induced via different insults in cultured cells. Micronuclei inKIF18AKO cells form stable nuclear envelopes characterized by increased recruitment of core and non-core nuclear envelope components and successful expansion of decondensing chromatin compared to those induced by microtubule drug washout or exposure to radiation. We also observed that lagging chromosomes, which lead to micronucleus formation, were positioned closer to the main chromatin masses, and further from the central spindle, inKIF18AKO cells. Our studies providein vivosupport to models suggesting that micronuclear fate depends on the sub-cellular location of late lagging chromosomes and suggest that not all micronuclei actively promote tumorigenesis.
Prefrontal cortical activity predicts the extra-place field spiking of hippocampal place cells
Authors: Yu Jai Y. , Frank Loren M. 
Published: November 2020

AbstractThe receptive field of a neuron describes the regions of a stimulus space where the neuron is consistently active. Sparse spiking outside of the receptive field is often considered to be noise, rather than a reflection of information processing. Whether this characterization is accurate remains unclear. We therefore contrasted the sparse, temporally isolated spiking of hippocampal CA1 place cells to the consistent, temporally adjacent spiking seen within their spatial receptive fields (“place fields”). We found that isolated spikes, which occur during locomotion, are more strongly phase coupled to hippocampal theta oscillations than adjacent spikes and, surprisingly, transiently express coherent representations of non-local spatial representations. Further, prefrontal cortical activity is coordinated with, and can predict the occurrence of future isolated spiking events. Rather than local noise within the hippocampus, sparse, isolated place cell spiking reflects a coordinated cortical-hippocampal process consistent with the generation of non-local scenario representations during active navigation.
Excess mortality across regions of Europe during the first wave of the COVID-19 pandemic – impact of the winter holiday travelling and government responses
Authors: Björk Jonas , Mattisson Kristoffer , Ahlbom Anders 
Published: November 2020

AbstractBackgroundThis aggregated population study of 219 regions in 11 European countries investigated the effect of the seemingly quasi-randomly assigned school winter holiday week on excess mortality associated with the COVID-19 pandemic during spring 2020. A secondary aim was to evaluate the impact of stringency and timing of the government responses to the early inflow of infected cases.MethodsRegional data on mortality week 14-23 in 2020 compared with the same period 2015-2019 were retrieved from Eurostat and national statistical agencies. Data on initial government responses were obtained from the Oxford COVID-19 Government Response Tracker. Variance-weighted least square regression was used with further adjustment for population density and age distribution.ResultsBeing a region with winter holiday exclusively in week 9 was in the adjusted analysis associated with 16 weekly excess deaths (95% confidence interval 13 to 20) per million inhabitants, which corresponds to 38% of the excess mortality during the study period in these regions. A more stringent response implemented in week 11, corresponding to 10 additional units on the 0-100 ordinal scale, was associated with 20 fewer weekly deaths (95% confidence interval 18 to 22) per million inhabitants.ConclusionsTravelling during winter holiday in week 9 was an amplifying event that contributed importantly to the excess mortality observed in the study area during the spring 2020. Timely government responses to the resulting early inflow of cases was associated with lower excess mortality.
Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics
Authors: Markin C.J. , Mokhtari D.A. , Sunden F. , Appel M.J. , Akiva E. , Longwell S.A. , Sabatti C. , Herschlag D. , Fordyce P.M. 
Published: November 2020

AbstractSystematic and extensive investigation of enzymes is needed to understand their extraordinary efficiency and meet current challenges in medicine and engineering. We present HT-MEK, a microfluidic platform for high-throughput expression, purification, and characterization of >1500 enzyme variants per experiment. For 1036 mutants of the alkaline phosphatase PafA, we performed >670,000 reactions to determine >5000 kinetic and physical constants for multiple substrates and inhibitors. These constants allowed us to uncover extensive kinetic partitioning to a misfolded state and isolate catalytic effects, revealing spatially contiguous “regions” of residues linked to particular aspects of function. These regions included active-site proximal residues but also extended to the enzyme surface, providing a map of underlying architecture that could not be derived from existing approaches. HT-MEK, using direct and coupled fluorescent assays, has future applications to a wide variety of problems ranging from understanding molecular mechanisms to medicine to engineering and design.One Sentence SummaryHT-MEK, a microfluidic platform for high-throughput, quantitative biochemistry, reveals enzyme architectures shaping function.