bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in Aerosol Production Across Oxygen Delivery Devices in Spontaneously Breathing Human Subjects
Authors: Iwashyna Theodore J. , Boehman Andre , Capecelatro Jesse , Cohn Amy M. , Cooke James M. , Costa Deena Kelly , Eakin Richard M. , Prescott Hallie C. , Woolridge Margaret S. 
Published: April 2020

We sought to assess whether HHFNC results in greater production of aerosolized particles than 6 liters per minute nasal cannula, using state-of-the-art techniques of aerosol measurement, in spontaneously breathing human volunteers in a simulated hospital room.For each volunteer, we first measured background aerosol levels in the room immediately prior to testing. We then measured aerosol levels while the healthy volunteer laid in bed - - with the head of bed at 30 degrees - - wearing the following oxygen delivery devices: (a) 6L/min nasal canula (NC) with humidification; (b) non-re-breather mask (NRB) with 15L/min gas flow, non-humidified; (c) HHFNC with 30L/min gas flow; (d) HHFNC with 60L/min gas flow. Two scanning mobility particle sizing (SMPS) systems (TSI 3080/3030, TSI 3080/3750) were used to measure aerosols 10 to 500 nanometer (nm) in size for each of the oxygen delivery devices.There was no variation in aerosol level within patients between room air, 6 L/min NC, 15 L/min NRB, 30 L/min HHFNC, and 60 L/min HHFNC, regardless of coughing.
Why lockdown? Simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the novel coronavirus
Authors: Killeen Gerry F. , Kiware Samson S 
Published: April 2020

SummaryHalf the world’s population is already under lock-down and the remainder will have to follow if the ongoing novel coronavirus 2019 (COVID-19) virus pandemic is to be contained. Faced with such brutally difficult decisions, it is essential that as many people as possible understand (1) why lock-down interventions represent the only realistic way for individual countries to contain their national-level epidemics before they turn into public health catastrophes, (2) why these need to be implemented so early, so aggressively and for such extended periods, and (3) why international co-operation to conditionally re-open trade and travel between countries that have successfully eliminated local transmission represents the only way to contain the pandemic at global level. Here we present simplified arithmetic models of COVID-19 transmission, control and elimination in user-friendly Shiny and Excel formats that allow non-specialists to explore, query, critique and understand the containment decisions facing their country and the world at large. Based on parameter values representative of the United Republic of Tanzania, which is still early enough in its epidemic cycle and response to avert a national catastrophe, national containment and elimination with less than 10 deaths is predicted for highly rigorous lock down within 5 weeks of the first confirmed cases and maintained for 15 weeks. However, elimination may only be sustained if case importation from outside the country is comprehensively contained by isolating for three weeks all incoming travellers, except those from countries certified as COVID-free in the future. Any substantive relaxation of these assumptions, specifically shortening the lock-down period, less rigorous lock-down or imperfect importation containment, may facilitate epidemic re-initiation, resulting in over half a million deaths unless rigorously contained a second time. Removing contact tracing and isolation has minimal impact on successful containment trajectories because high incidence of similar mild symptoms caused by other common pathogens attenuates detection success of COVID-19 testing. Nevertheless, contact tracing is recommended as an invaluable epidemiological surveillance platform for monitoring and characterizing the epidemic, and for understanding the influence of interventions on transmission dynamics.
Knowledge and practice of preventive measures against COVID-19 infection among pregnant women in a low-resource African setting
Authors: Nwafor Johnbosco Ifunanya , Aniukwu Joseph Kenechi , Anozie Bonaventure Okechukwu , Ikeotuonye Arinze Chidiebere 
Published: April 2020

AbstractBackgroundCoronavirus disease pandemic has resulted in death of thousands of people across several countries. Several preventive measures have been recommended to halt the spread of the disease and its associated mortality. However, the level knowledge and practice of these preventive measures against COVID-19 infection among pregnant women, which constitute vulnerable groups, are yet to be evaluated.AimTo determine the knowledge and practice of preventive measures against COVID-19 infection among pregnant women in Abakaliki.Materials and MethodsThis was a self-administered questionnaire-based cross-sectional study conducted from February 1, 2020 to March 31, 2020 among 284 antenatal clinic attendees at Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State. A pretested and validated questionnaire was used to collect the data. Data analysis was done using SPSS version 22.ResultsOf 284 participants, 60.9% (n=173) had adequate knowledge of the preventive measures against COVID-19 infection. However, the overall practice of these preventive measures among the participants were poor as 69.7% of the participants were not practicing the preventive measures against the coronavirus. The determinants of poor practice of the preventive measures among the participants were being in age group 31-40 years (AOR=2.04, 95%CI: 1.26 - 5.37, p=0.022), married (AOR=2.99, 95%CI: 1.40 - 6.33, p=0.035) grandmultiparous (AOR=3.11, 95%CI: 1.32 - 6.56, p=0.021), residing in rural area (AOR=2.08, 95%CI: 1.32 - 4.05, p=0.031), and having no formal education (AOR=6.73, 95%CI: 2.66 - 18.34, p=0.002).ConclusionThe study showed that most of the participants had adequate knowledge of preventive measures against COVID-19 infection but the practice of these preventive measures were poor among the participants.
Community Memory of COVID-19 Infections Post Lockdown as a Surrogate for Incubation Time
Authors: Prakash Meher K. 
Published: April 2020

AbstractIf the knowledge of the incubation time is helpful in designing non-pharmaceutical interventions such as quarantine measures, can one use the number of cases arising after a lockdown to check (a) if our assumptions of the incubation time were correct and (b) if the quarantine measures were as successful as they could theoretically be. These are the two questions we raise by studying the number of new cases arising after lockdowns in a few European countries. The analysis which purely relies on the publicly available data of the numbers of new infections, rather than extensive contact tracing of individual patients, suggests a “memory” of the infections in the community with a median of 13.3 days. This distribution of the memory of infections which may even be considered as a surrogate of the incubation time in a perfect lockdown, suggests that even a perfect quarantine of 30 days is only 90% complete.
Cadherins regulate nuclear topography and function of developing ocular motor circuitry
Authors: Knüfer Athene , Diana Giovanni , Walsh Gregory S. , Clarke Jonathan , Guthrie Sarah 
Published: April 2020

AbstractIn the vertebrate central nervous system, groups of functionally-related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.
GABABreceptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals
Authors: Bhandari Pradeep , Vandael David , Fernández-Fernández Diego , Fritzius Thorsten , Kleindienst David , Montanaro Jacqueline , Gassmann Martin , Jonas Peter , Kulik Akos , Bettler Bernhard , Shigemoto Ryuichi , Koppensteiner Peter 
Published: April 2020

SummaryThe connection from medial habenula (MHb) to interpeduncular nucleus is critical for aversion- and addiction-related behaviors. This pathway is unique in selective expression of R-type voltage-gated Ca2+channels (Cav2.3) in its terminals, and robust potentiation of release via presynaptic GABABreceptors (GBRs). To understand the mechanism underlying this peculiar GBR effect, we examined the presynaptic localization and function of Cav2.3, GBR, and its auxiliary subunits, K+-channel tetramerization domain-containing (KCTD) proteins. We found selective co-expression of KCTD12b and Cav2.3 at the presynaptic active zone. GBR-mediated potentiation remained intact in KCTD12b KO mice but lasted significantly shorter. This impairment was associated with increased release and an insertion of KCTD8 into the active zone. In heterologous cells, we found direct binding of KCTD8 and KCTD12b to Cav2.3, and potentiation of Cav2.3 currents by KCTD8. The unexpected interaction of Cav2.3 with KCTDs therefore provides a means to scale synaptic strength independent of GBR activation.
Hypomethylated poplars show higher tolerance to water deficit and highlight a dual role for DNA methylation in shoot meristem: regulation of stress response and genome integrity
Authors: Sow M.D. , Le Gac A-L. , Fichot R. , Lanciano S. , Delaunay A. , Le Jan I. , Lesage-Descauses M-C. , Citerne S. , Caius J. , Brunaud V. , Soubigou-Taconnat L. , Cochard H. , Segura V. , Chaparro C. , Grunau C. , Daviaud C. , Tost J. , Brignolas F. , Strauss S.H. , Mirouze M. , Maury S. 
Published: April 2020

AbstractAs fixed and long living organisms subjected to repeated environmental stresses, trees have developed mechanisms such as phenotypic plasticity that help them to cope with fluctuating environmental conditions. Here, we tested the role DNA methylation as a hub of integration, linking plasticity and physiological response to water deficit in the shoot apical meristem of the model tree poplar (Populus). Using a reverse genetic approach, we compared hypomethylated RNAi-ddm1lines to wild-type trees for drought tolerance. An integrative analysis was realized with phytohormone balance, methylomes, transcriptomes and mobilomes.Hypomethylated lines were more tolerant when subjected to moderate water deficit and were intrinsically more tolerant to drought-induced cavitation. The alteration of theDDM1machinery induced variation in DNA methylation in a cytosine context dependent manner, both in genes and transposable elements. Hypomethylated lines subjected to water deficit showed altered expression of genes involved in phytohormone pathways, such as salicylic acid and modified hormonal balance. Several transposable elements showed stress- and/or line-specific patterns of reactivation, and we could detect copy number variations for two of them in stressedddm1lines.Overall, our data highlight two major roles for DNA methylation in the shoot apical meristem: control of stress response and plasticity through transduction of hormone signaling and maintenance of genome integrity through the control of transposable elements.
Estimating COVID-19 outbreak risk through air travel
Authors: Daon Y. , Thompson R.N. , Obolski U. 
Published: April 2020

AbstractBackgroundSubstantial limitations have been imposed on passenger air travel to reduce transmission of SARS-CoV-2 between regions and countries. However, as case numbers decrease, air travel will gradually resume. We considered a future scenario in which case numbers are low and air travel returns to normal. Under that scenario, there will be a risk of outbreaks in locations worldwide due to imported cases. We estimated the risk of different locations acting as sources of future COVID-19 outbreaks elsewhere.MethodsWe use modelled global air travel data and population density estimates from locations worldwide to analyse the risk that 1364 airports are sources of future COVID-19 outbreaks. We use a probabilistic, branching-process based approach that considers the volume of air travelers between airports and the reproduction number at each location, accounting for local population density.ResultsUnder the scenario we model, we identify airports in East Asia as having the highest risk of acting as sources of future outbreaks. Moreover, we investigate the locations most likely to cause outbreaks due to air travel in regions that are large and potentially vulnerable to outbreaks: India, Brazil and Africa. We find that outbreaks in India and Brazil are most likely to be seeded by individuals travelling from within those regions. We find that this is also true for less vulnerable regions, such as the United States, Europe, and China. However, outbreaks in Africa due to imported cases are instead most likely to be initiated by passengers travelling from outside the continent.ConclusionsVariation in flight volumes and destination population densities create a non-uniform distribution of the risk that different airports pose of acting as the source of an outbreak. Accurate quantification of the spatial distribution of outbreak risk can therefore facilitate optimal allocation of resources for effective targeting of public health interventions.
The focus and timing of COVID-19 pandemic control measures under healthcare resource constraints
Authors: Wei Chen , Wang Zhengyang , Liang Zhichao , Liu Quanying 
Published: April 2020

AbstractGeneralizing COVID-19 control strategies in one community to others is confounded by community’s unique demographic and socioeconomic attributes. Here we propose a tailored dynamic model accounting for community-specific transmission controls and medical resource availability. We trained the model using data from Wuhan and applied it to other countries. We show that isolating suspected cases is most effective in reducing transmission rate if the intervention starts early. Having more hospital beds provides leverage that diminishes with delayed intervention onset. The importance of transmission control in turn increases by 65% with a 7-day delay. Furthermore, prolonging outbreak duration by applying an intermediate, rather than strict, transmission control would not prevent hospital overload regardless of bed capacity, and would likely result in a high ratio (21% ∼ 84%) of the population being infected but not treated. The model could help different countries design control policies and gauge the severity of suppression failure.
Prognostic significance of compound physiology variables in oesophageal cancer
Authors: Powell Arfon G M T , Eley Catherine , Coxon Alexandra H , Chin Carven , Bailey Damian M , Lewis Wyn G ,   South East Wales Oesophagogastric Cancer Collaborative
Published: April 2020

AbstractAimsObjective identification of patient risk profile in Oesophageal Cancer (OC) surgery is critical. This study aimed to evaluate to what extent cardiorespiratory fitness and select metabolic factors predict clinical outcome.MethodsConsecutive 186 patients were recruited (median age 69 yr. 160 male, 138 neoadjuvant therapy). All underwent pre-operative cardiopulmonary exercise testing to determine peak oxygen uptake , anaerobic threshold (AT), and ventilatory equivalent for carbon dioxide . Cephalic venous blood was assayed for serum C-reactive protein (CRP), albumin, and full blood count. Primary outcome measures were Morbidity Severity Score (MSS), and Overall Survival (OS).ResultsMSS (Clavien-Dindo >2) developed in 33 (17.7%) and was related to elevated CRP (AUC 0.69, p=0.001) and lower V·O2Peak (AUC 0.33, p=0.003). Dichotomisation of CRP (above 10mg/L) and V·O2Peak (below 18.6mL/kg/min) yielded adjusted Odds Ratios (OR) for MSS CD>2, of 4.01 (p=0.002) and 3.74 (p=0.002) respectively. OC recurrence occurred in 36 (19.4%) and 69 (37.1%) patients died. On multivariable analysis; pTNM stage (Hazard Ratio (HR) 2.20, p=0.001), poor differentiation (HR 2.20, p=0.010), resection margin positivity (HR 2.33, p=0.021), and MSS (HR 4.56, p<0.001) were associated with OS.ConclusionsCRP and V·O2Peak are collective independent risk factors that can account for over half of OC survival variance.
ZBTB18 inhibits SREBP-dependent fatty acid synthesis by counteracting CTBPs and KDM1A/LSD1 activity in glioblastoma
Authors: Ferrarese R. , Izzo A. , Andrieux G. , Lagies S. , Bartmuss J.P. , Masilamani A.P. , Wasilenko A. , Osti D. , Faletti S. , Schulzki R. , Shuai Y. , Kling E. , Ribecco V. , Heiland D.H. , Tholen S.G. , Prinz M. , Pelicci G. , Kammerer B. , Börries M. , Carro M.S. 
Published: April 2020

AbstractEnhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression of enzymes involved in fatty acid and cholesterol synthesis. Yet, little is known about the precise mechanism regulating SREBP gene expression in glioblastoma. Here, we show that a novel interaction between the co-activator/co-repressor CTBP and the tumor suppressor ZBTB18 regulates the expression of SREBP genes. Our study points at CTBP1/2 and LSD1 as co-activators of SREBP genes whose complex functional activity is altered by ZBTB18. ZBTB18 binding to the SREBP gene promoters is associated with reduced LSD1 demethylase activity of H3 active marks leading to increased di-methylation of lysine 4 (H3K4me2). Concomitantly, we observed increased di-methylation of lysine 9 (H3K9me2), and decrease of the active mark H3K4me3 with consequent repression of the SREBP genes. In line with our findings, lipidomic analysis shows a reduction of several phospholipid species upon ZBTB18 expression. Our results outline a new epigenetic mechanism enrolled by ZBTB18 and its cofactors to regulate fatty acid synthesis that could be targeted to treat glioblastoma patients.
Structural Model of the Proline-rich Domain of Huntingtin exon-1 fibrils
Authors: Falk A. S. , Bravo-Arredondo J. M. , Varkey J. , Pacheco S. , Langen R. , Siemer A. B. 
Published: April 2020

AbstractHuntington’s disease (HD) is a heritable neurodegenerative disease that is caused by a CAG expansion in the first exon of the huntingtin gene. This expansion results in an elongated polyglutamine (polyQ) domain that increases the propensity of huntingtin exon-1 (HTTex1) to form cross-β fibrils. While the polyQ domain is important for fibril formation, the dynamic, C-terminal proline-rich domain (PRD) of HTTex1 makes up a large fraction of the fibril surface. Because potential fibril toxicity has to be mediated by interactions of the fibril surface with its cellular environment, we wanted to model the conformational space adopted by the PRD. We ran 800 ns long molecular dynamics (MD) simulations of the PRD using an explicit water model optimized for intrinsically disordered proteins. These simulations accurately predicted our previous solid-state NMR data and newly acquired EPR DEER distances, lending confidence in their accuracy. The simulations show that the PRD generally forms an imperfect polyproline II (PPII) helical conformation. The two polyproline (polyP) regions within the PRD stay in a PPII helix for most of the simulation, whereas occasional kinks in the proline rich linker region cause an overall bend in the PRD structure. The dihedral angles of the glycine at the end of the second polyP region are very variable, effectively decoupling the highly dynamic 12 C-terminal residues from the rest of the PRD.Statement of SignificanceHD is caused by a polyQ expansion in the exon-1 of huntingtin, which results in the formation of fibrillar huntingtin aggregates. Although the polyQ domain is the site of the disease-causing mutation, the PRD domain of HTTex1 is important for fibril toxicity and contains many epitopes of fibril-specific HTTex1 antibodies. Here, we present a structural and dynamic model of the highly dynamic PRD domain using a combination of EPR, solid-state NMR, and MD simulations. This model paves the way for studying known HTTex1 fibril specific binders and designing new ones.
Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations
Authors: Gur Mert , Taka Elhan , Yilmaz Sema Zeynep , Kilinc Ceren , Aktas Umut , Golcuk Mert 
Published: April 2020

ABSTRACTSince its first recorded appearance in December 2019, a novel coronavirus (SARS-CoV-2) causing the disease COVID-19 has resulted in more than 2,000,000 infections and 128,000 deaths. Currently there is no proven treatment for COVID-19 and there is an urgent need for the development of vaccines and therapeutics. Coronavirus spike glycoproteins play a critical role in coronavirus entry into the host cells, as they provide host cell recognition and membrane fusion between virus and host cell. Thus, they emerged as popular and promising drug targets. Crystal structures of spike protein in its closed and open states were resolved very recently in March 2020. These structures comprise 77% of the sequence and provide almost the complete protein structure. Based on down and up positions of receptor binding domain (RBD), spike protein can be in a receptor inaccessible closed or receptor accessible open state, respectively. Starting from closed and open state crystal structures, and also 16 intermediate conformations, an extensive set of all-atom molecular dynamics (MD) simulations in the presence of explicit water and ions were performed. Simulations show that in its down position, RBD has significantly lower mobility compared to its up position; probably caused by the 6 interdomain salt bridges of RBD in down position compared to 3 in up position. Free energy landscapes based on MD simulations revealed a semi-open state located between closed and open states. Minimum energy pathway between down and up positions comprised a gradual salt bridge switching mechanism. Furthermore, although significantly lower than open state, ACE2 binding surface of RBD contained a partial solvent accessibility in its closed state.
Subcircuits of deep and superficial CA1 place cells support efficient spatial coding across heterogeneous environments
Authors: Sharif Farnaz , Tayebi Behnam , Buzsáki György , Royer Sebastien , Fernandez-Ruiz Antonio 
Published: April 2020

AbstractThe hippocampus is thought to guide navigation by forming a cognitive map of space. However, the behavioral demands for such a map can vary depending on particular features of a given environment. For example, an environment rich in cues may require a finer resolution map than an open space. It is unclear how the hippocampal cognitive map adjusts to meet these distinct behavioral demands. To address this issue, we examined the spatial coding characteristics of hippocampal neurons in mice and rats navigating different environments. We found that CA1 place cells located in the superficial sublayer were more active in cue-poor environments, and preferentially used a firing rate code driven by intra-hippocampal inputs. In contrast, place cells located in the deep sublayer were more active in cue-rich environments and expressed a phase code driven by entorhinal inputs. Switching between these two spatial coding modes was supported by the interaction between excitatory gamma inputs and local inhibition.