bluuebunny/crossref_metadata_2025_split huggingface dataset:
How did COVID-19 measures impact sexual behaviour and access to HIV/STI services in Panama? Results from a national cross-sectional online survey
Authors: Gabster Amanda , Erausquin Jennifer Toller , Michielsen Kristien , Mayaud Philippe , Pascale Juan Miguel , Escalé Carles Pericas , Marks Michael , Katz Jennifer , Talavero Gonzalo Cabezas , de Argote Marilu , Murillo Anet , Tucker Joseph D. 
Published: February 2021

AbstractObjectivesTo describe perceived changes in sexual behaviours, including virtual sex (sexting and cybersex), and access to HIV/STI testing and care during COVID-19 measures in Panama. Methods We conducted an online cross-sectional survey from August 8 to September 12, 2020, among adults (≥18 years) residing in Panama. Participants were recruited through social media. Questions included demographics, access to HIV/STI testing and HIV care and sexual behaviours three months before COVID-19 social distancing measures and during social distancing measures (COVID-19 measures). Logistic regression was used to identify associations between variables and behavioural changes.ResultsWe recruited 960 participants; 526 (54.8%) identified as cis-women, 366 (38.1%) cis-men, and 68 (7.1%) non-binary or another gender; median age was 28y (IQR:23-37y), 531/957 (55.5%) were of mixed-ethnicity (mixed-Indigenous/European/Afro-descendant ancestry). Before COVID-19 measures, virtual sex was reported by 38.5% (181/470) cis-women, 58.4% (184/315) cis-men and 45.0% (27/60) non-binary participants; during COVID-19 measures, virtual sex increased among 17.2% cis-women, 24.7% cis-men and 8.9% non-binary participants. During COVID-19 measures, 230/800 [28.8%] of participants reported decreased casual sex compared to pre-COVID-19 measures. Compared to pre-COVID-19 measures, decreased casual sex were reported more frequently during COVID-19 measures by cis-men compared to cis-women (39.2% versus 22.9%, urban/rural adjusted odds ratio [AOR]=2.17, 95% confidence interval [CI]:1.57-3.01); and by Afro-descendant compared to mixed-ethnicity participants (40.0% versus 29.8%, AOR=1.78, 95%CI:1.07-2.94). Compared to no change in virtual sex (16.8%), increase in virtual sex (38.5%, AOR=1.78, 95%CI:1.10-2.88); and decreased virtual sex (86.7%, AOR=16.53, 95%CI:7.74-35.27) were associated with decreased casual sex encounters. During COVID-19 measures, HIV/STI testing could not be obtained by 58.0%(58/100) participants who needed a test, and interrupted HIV care was reported by 53.3% (8/15) HIV-positive participants.ConclusionsCOVID-19 measures in Panama were associated with a decrease in casual sex among cis-men and Afro-descendant peoples, whilst access to HIV/STI testing and care was seriously disrupted.
Outcomes following out-of-hours cholecystectomy: A systematic review and meta-analysis
Authors: Bhat Sameer , Varghese Chris , Xu William , Barazanchi Ahmed W.H. , Ratnayake Bathiya , O’Grady Gregory , Windsor John A. , Wells Cameron I. 
Published: February 2021

ABSTRACTBackgroundCholecystectomy is one of the most commonly performed abdominal operations. Demands on acute operating theatre availability have led to out-of-hours (evenings, nights, or weekend) cholecystectomy being performed, although it is not known whether outcomes differ between out-of-hours and in-hours (daytime on weekdays) cholecystectomy.ObjectiveThis systematic review and meta-analysis aimed to compare outcomes following out-of-hoursversusin-hours urgent cholecystectomy.MethodsMEDLINE, EMBASE and Scopus databases were systematically searched from inception to December 2020 for studies comparing outcomes from out-of-hours and in-hours urgent cholecystectomy in adults. The outcomes of interest were rates of bile leakage, bile duct injury (BDI), overall post-operative complications, conversion to open cholecystectomy, specific intra- and post-operative complications, length of stay (LOS), readmission and mortality. Sensitivity analysis of adjusted multivariate results was also performed.ResultsIn total, 194,135 urgent cholecystectomies (30,001 out-of-hours; 164,134 in-hours) from 11 studies were included. Most studies were of high (64%) or medium (18%) quality. There were no differences between out-of-hours and in-hours cholecystectomy for rates of bile leakage, BDI, overall post-operative complications, conversion to open cholecystectomy, operative duration, readmission, mortality, and post-operative LOS. Higher rates of post-operative sepsis (odds ratio (OR) 1.58, 95% CI: 1.04-2.41; p=0.03) and pneumonia (OR 1.55, 95% CI: 1.06-2.26; p=0.02) were observed following out-of-hours cholecystectomy on univariate meta-analysis but not on adjusted multivariate meta-analysis.ConclusionsThere was no increased risk or difference in specific complications associated with out-of-hours compared with in-hours urgent cholecystectomy.
DMRscaler: A Scale-Aware Method to Identify Regions of Differential DNA Methylation Spanning Basepair to Multi-Megabase Features
Authors: Bondhus Leroy , Wei Angela , Arboleda Valerie A. 
Published: February 2021

ABSTRACTBackgroundPathogenic mutations in genes that control chromatin function have been implicated in rare genetic syndromes. These chromatin modifiers exhibit extraordinary diversity in the scale of the epigenetic changes they affect, from single basepair modifications by DNMT1 to whole genome structural changes by PRM1/2. Patterns of DNA methylation are related to a diverse set of epigenetic features across this full range of epigenetic scale, making DNA methylation valuable for mapping regions of general epigenetic dysregulation. However,existing methods are unable to accurately identify regions of differential methylation across this full range of epigenetic scale directly from DNA methylation data.ResultsTo address this, we developed DMRscaler, a novel method that uses an iterative windowing procedure to capture regions of differential DNA methylation (DMRs) ranging in size from single basepairs to whole chromosomes. We benchmarked DMRscaler against several DMR callers in simulated and natural data comparing XX and XY peripheral blood samples. DMRscaler was the only method that accurately called DMRs ranging in size from 100 bp to 1 Mb (pearson’s r = 0.96) and up to 152 Mb on the X-chromosome. We then analyzed methylation data from rare-disease cohorts that harbor chromatin modifier gene mutations in NSD1, EZH2, and KAT6A where DMRscaler identified novel DMRs spanning gene clusters involved in development.ConclusionTaken together, our results show DMRscaler is uniquely able to capture the size of DMR features across the full range of epigenetic scale and identify novel, co-regulated regions that drive epigenetic dysregulation in human disease.
A novel capsid protein network allows the characteristic inner membrane structure of Marseilleviridae giant viruses
Authors: Chihara Akane , Burton-Smith Raymond N. , Kajimura Naoko , Mitsuoka Kaoru , Okamoto Kenta , Song Chihong , Murata Kazuyoshi 
Published: February 2021

AbstractMarseilleviridae is a family of the new order of giant viruses, which exhibit a characteristic inner membrane. Here, we investigated the entire structure of tokyovirus, a species of Marseillevirus at 7.7 Å resolution using 1 MV high-voltage cryo-EM and single particle analysis. The minor capsid lattice formed by five proteins, shows a novel structure compared to other icosahedral giant viruses. Under the minor capsid proteins, scaffold proteins connect two five-fold vertices and interact with the inner membrane. Previously reported giant viruses utilise “tape measure” proteins, proposed to control its capsid size, which could not be identified in tokyovirus, but scaffold proteins appear to perform a similar role. A density on top of the major capsid protein was identified, which suggested to be a 14kDa glycoprotein. Our observations suggest that the icosahedral particle of Marseilleviridae is constructed with a novel capsid protein network, which allows the characteristic inner membrane structure.
Cold-acclimation induces life stage-specific responses in the cardiac proteome of Western painted turtles (Chrysemys picta bellii): implications for anoxia tolerance
Authors: Alderman Sarah L. , Riggs Claire L. , Bullingham Oliver , Gillis Todd E. , Warren Daniel E. 
Published: February 2021

AbstractWestern painted turtles(Chrysemys picta bellii)are the most anoxia-tolerant tetrapod. Survival time improves at low temperature and during ontogeny, such that adults acclimated to 3°C survive far longer without oxygen than either warm-acclimated adults or cold-acclimated hatchlings. Since protein synthesis is rapidly suppressed to save energy at the onset of anoxia exposure, this study tested the hypothesis that cold-acclimation would evoke preparatory changes in protein expression that would support enhanced anoxia survival in adult but not hatchling turtles. To test this, adult and hatchling turtles were acclimated to either 20°C (warm) or 3°C (cold) for 5 weeks, and then the heart ventricles were collected for quantitative proteomic analysis using labeled isobaric tags and mass spectrometry. The relative abundances of 1316 identified proteins were compared between temperatures and developmental stages. The effect of cold-acclimation on the cardiac proteome was most evident when life stage was included as a covariable, suggesting that ontogenic differences in anoxia tolerance may be predicated on successful maturation of the heart from its hatchling to adult form and, only after this maturation occurs, will cold-acclimation induce protein expression changes appropriate for supporting heart function during prolonged anoxia. The main differences between the hatchling and adult cardiac proteomes reflect an increase in metabolic scope that included more myoglobin and increased investment in both aerobic and anaerobic energy pathways. Mitochondrial structure and function were key targets of life stage- and temperature-induced changes to the cardiac proteome, including reduced complex II proteins in cold-acclimated adults that may help down-regulate the electron transport system and avoid succinate accumulation during anoxia. Therefore, targeted cold-induced changes to the cardiac proteome may be a contributing mechanism for stagespecific anoxia tolerance in turtles.
Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens
Authors: Goldstein Stephen A. , Brown Joe , Pedersen Brent S. , Quinlan Aaron R. , Elde Nels C. 
Published: February 2021

AbstractThe ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in the last twenty years. Enzootic and epizootic coronaviruses of diverse lineages also pose a significant threat to livestock, as most recently observed for virulent strains of porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea-associated coronavirus (SADS-CoV). Unique to RNA viruses, coronaviruses encode a proofreading exonuclease (ExoN) that lowers point mutation rates to increase the viability of large RNA virus genomes, which comes with the cost of limiting virus adaptation via point mutation. This limitation can be overcome by high rates of recombination that facilitate rapid increases in genetic diversification. To compare dynamics of recombination between related sequences, we developed an open-source computational workflow (IDPlot) to measure nucleotide identity, locate recombination breakpoints, and infer phylogenetic relationships. We analyzed recombination dynamics among three groups of coronaviruses with noteworthy impacts on human health and agriculture:SARSr-CoV, Betacoronavirus-1, and SADSr-CoV. We found that all three groups undergo recombination with highly diverged viruses from sparsely sampled or undescribed lineages, which can disrupt the inference of phylogenetic relationships. In most cases, no parental origin of recombinant regions could be found in genetic databases, suggesting that much coronavirus diversity remains unknown. These patterns of recombination expand the genetic pool that may contribute to future zoonotic events. Our results also illustrate the limitations of current sampling approaches for anticipating zoonotic threats to human and animal health.
The yeast eIF2 kinase Gcn2 facilitates H2O2-mediated feedback inhibition of both protein synthesis and ER oxidative folding during recombinant protein production
Authors: Gast Veronica , Campbell Kate , Campos Cecilia Picazo , Engqvist Martin , Siewers Verena , Molin Mikael 
Published: February 2021

AbstractRecombinant protein production is a known source of oxidative stress. Knowledge of which ROS are involved or the specific growth phase in which stress occurs however remains lacking. Using modern, hypersensitive genetic H2O2-specific probes, micro-cultivation and continuous measurements in batch culture, we observed H2O2accumulation during and following the diauxic shift in engineeredSaccharomyces cerevisiae, correlating with peak α-amylase production. In agreement with previous studies supporting a role of the translation initiation factor kinase Gcn2 in the response to H2O2, we find Gcn2-dependent phosphorylation of eIF2α to increase alongside translational attenuation in strains engineered to produce large amounts of α-amylase. Gcn2 removal significantly improved α-amylase production in two previously optimized high-producing strains, but not in the wild-type. Gcn2-deficiency furthermore reduced intracellular H2O2levels and the unfolded protein response whilst expression of antioxidants and the ER disulfide isomerasePDI1increased. These results suggest protein synthesis and ER oxidative folding to be coupled and subject to feedback inhibition by H2O2.ImportanceReactive oxygen species (ROS) accumulate during recombinant protein production both in yeast and Chinese hamster ovary cells, two of the most popular organisms used in the multi-million dollar protein production industry. Here we document increased H2O2in the cytosol of yeast cells producing α-amylase. Since H2O2predominantly targets the protein synthesis machinery and activates the translation initiation factor kinase Gcn2, we removed Gcn2, resulting in increased recombinant α-amylase production in two different previously engineered high-producing protein production strains. Removal of this negative feed-back loop thus represents a complementary strategy for improving recombinant protein production efforts currently used in yeast. Gcn2-deficiency also increased the expression of antioxidant genes and the ER-foldasePDI1, suggesting that protein synthesis and ER oxidative folding are linked and feed-back regulated via H2O2. Identification of additional components in this complex regulation may further improve protein production and contribute to the development of novel protein-based therapeutic strategies.
Parallel Rap1>RalGEF>Ral and Ras signals sculpt theC. elegansnervous system
Authors: Mardick Jacob I. , Rasmussen Neal R. , Wightman Bruce , Reiner David J. 
Published: February 2021

ABSTRACTRas is the most commonly mutated oncogene in humans and uses three oncogenic effectors: Raf, PI3K, and RalGEF activation of Ral. Understanding the importance of RalGEF>Ral signaling in cancer is hampered by the paucity of knowledge about their function in animal development, particularly in cell movements. We found that mutations that disrupt function of RalGEF or Ral enhance migration phenotypes of mutations in genes with established roles in cell migration. We used as a model the migration of the canal associated neurons (CANs), and validated our results in HSN cell migration, neurite guidance, and general animal locomotion. These functions of RalGEF and Ral are specific to their control of Ral signaling output rather than other published functions of these proteins. In this capacity Ral functions cell autonomously as a permissive developmental signal. In contrast, we observed Ras, the canonical activator of RalGEF>Ral signaling in cancer, to function as an instructive signal. Furthermore, we unexpectedly identified a function for the close Ras relative, Rap1, consistent with activation of RalGEF>Ral. These studies define functions of RalGEF>Ral, Rap1 and Ras signaling in morphogenetic processes that fashion the nervous system. We have also defined a model for studying how small GTPases partner with downstream effectors. Taken together, this analysis defines novel molecules and relationships in signaling networks that control cell movements during development of the nervous system.
Microbiota analysis of rural and urban surface waters and sediments in Bangladesh identifies human waste as driver of antibiotic resistance
Authors: McInnes Ross Stuart , uz-Zaman Md. Hassan , Alam Imam Taskin , Ho Siu Fung Stanley , Moran Robert A. , Clemens John D. , Islam Md. Sirajul , van Schaik Willem 
Published: February 2021

AbstractIn many low- and middle-income countries antibiotic resistant bacteria spread in the environment due to inadequate treatment of wastewater and the poorly regulated use of antibiotics in agri- and aquaculture. Here we characterised the abundance and diversity of antibiotic-resistant bacteria and antibiotic resistance genes in surface waters and sediments in Bangladesh through quantitative culture of Extended-Spectrum Beta-Lactamase (ESBL)-producing coliforms and shotgun metagenomics. Samples were collected from highly urbanised settings (n= 7), from rural ponds with a history of aquaculture-related antibiotic use (n= 11) and from rural ponds with no history of antibiotic use (n= 6). ESBL-producing coliforms were found to be more prevalent in urban samples than in rural samples. Shotgun sequencing showed that sediment samples were dominated by the phylum Proteobacteria (on average 73.8% of assigned reads), while in the water samples Cyanobacteria (on average 60.9% of assigned reads) were the predominant phylum. Antibiotic resistance genes were detected in all samples, but their abundance varied 1,525-fold between sites, with the highest levels of antibiotic resistance genes being present in urban surface water samples. We identified an IncQ1 sulphonamide resistance plasmid ancestral to the widely studied RSF1010 in one of the urban water samples. The abundance of antibiotic resistance genes was significantly correlated (R2= 0.73;P= 8.9 × 10−15) with the abundance of bacteria originating from the human gut, which suggests that the release of untreated sewage is a driver for the spread of environmental antibiotic resistance genes in Bangladesh, particularly in highly urbanised settings.ImportanceLow- and middle-income countries (LMICs) have higher burdens of multidrug-resistant infections than high-income countries and there is thus an urgent need to elucidate the drivers of the spread of antibiotic-resistant bacteria in LMICs. Here we study the diversity and abundance of antibiotic resistance genes in surface water and sediments from rural and urban settings in Bangladesh. We found that urban surface waters are particularly rich in antibiotic resistance genes, with a higher number of them associated with plasmids indicating that they are more likely to spread horizontally. The abundance of antibiotic resistance genes was strongly correlated with the abundance of bacteria that originate from the human gut, suggesting that uncontrolled release of human waste is a major driver for the spread of antibiotic resistance in the urban environment. Improvements in sanitation in LMICs may thus be a key intervention to reduce the dissemination of antibiotic resistant bacteria.
Follow-up of a hospital cohort during the first 3,530 suspected cases of COVID-19 in Sao Jose do Rio Preto, Sao Paulo, Brazil
Authors: Pacca Carolina Colombelli , Zini Nathalia , Versiani Alice F. , de O. Lobl Edoardo E. , Milhim Bruno H. G. A. , Campos Guilherme R. F. , Moraes Marília M. , dos Santos Thayza M.I.L , Dourado Fernanda S. , Marques Beatriz C. , da Rocha Leonardo C. , dos Santos Andresa L , da Silva Gislaine C.D. , Ruiz Leonardo G. P. , Nicesio Raphael , Queiroz Flávia , Reis Andreia F. N. , da Silva Natal S. , Nogueira Maurício L. , Estofolete Cássia F. 
Published: February 2021

AbstractIntroductionIn a global context, COVID-19 is the most significant health threat in the present days, evidenced by the fact that, in just over four months, SARS-CoV-2 has spread to 171 countries, reaching a Pandemic status. Most patients with COVID-19 have a mild course of the disease. However, approximately 20% develop severe illness with a high mortality rate which is associated with age, comorbidities, and immunosuppression. Epidemiological studies are used to reveal the extent of viral spread in homes, communities, and hospitals. Thus, preventive and control measures can be established by the authorities.ObjectiveIn this study, patients with suspect COVID-19 symptoms who search for hospital care at the city of Sao José do Rio Preto (Sao Paulo, Brazil) were monitored, in order to identify the first case of this new disease in the region. In the first two months (March and April), more than 3000 individuals looked for the public and private health system with suspected respiratory symptoms, but only 164 (8.4%) were COVID-19 confirmed.ResultsFrom those, males (56.1%) and patients of the age distribution of 16-59 (91.2%), with diarrhea (22.2%), runny nose (25%), altered taste (15.9%), and anosmia (11.6%) presented statistical significance, although none comorbidities were related with COVID-19 occurrence. The odds ratio analysis supports this finding. Days of onset of symptoms are positively associated with whit viral load, and the same happens with the occurrence of symptoms (dyspnea and low saturation).
Cellular and biochemical response to chaperone versus substrate reduction therapies in neuropathic Gaucher disease
Authors: Ivanova Margarita , Dao Julia , Kasaci Neil , Adewale Benjamin , Nazari Shaista , Noll Lauren , Fikry Jacqueline , Sanati Armaghan Hafez , Goker-Alpan Ozlem 
Published: February 2021

AbstractGaucher disease (GD) is caused by the deficiency of the lysosomal membrane enzyme glucocerebrosidase (GCase), and the subsequent accumulation of its substrate, glucosylceramide substrate (GC). Mostly missense mutations of the glucocerebrosidase gene (GBA) lead to GCase misfolding and inhibiting the lysosome’s proper trafficking. The accumulated GC leads to lysosomal dysfunction and impairs the autophagy pathway.GD types 2 and 3 (GD2-3), or the neuronopathic forms, affect not only the Central Nervous System (CNS) but also have severe systemic involvement and progressive bone disease. Enzyme replacement therapy (ERT) successfully treats the hematologic manifestations; however, due to the lack of equal distribution of the recombinant enzyme in different organs, it has no impact on the nervous system and has minimal effect on bone involvement. Small molecules have the potential for better tissue distribution. Ambroxol (AMB) is a pharmacologic chaperone that partially recovers the mutated GCase activity and crosses the blood-brain barrier. Eliglustat (EGT) works by inhibiting UDP-glucosylceramide synthase, an enzyme that catalyzes the GC biosynthesis, reducing a GC influx load into the lysosome. Substrate reduction therapy (SRT) using EGT is associated with improvement in GD bone marrow burden score and bone mineral density.The effects of EGT and ABX on GCase activity and autophagy-lysosomal pathway (ALP) were assessed in primary cell lines derived from patients with GD2-3 and compared to cell lines from healthy controls. While both compounds enhanced GCase activity in control cells, an individualized response was observed in cells from patients with GD2-3 that varied withGBAmutations. EGT and AMB enhanced the formation of lysosomal/ late endosomal compartments and autophagy, and this effect was independent ofGBAmutations. Both AMB and EGT increased mitochondrial mass and density in GD2-3 fibroblasts, suggesting enhancement of the mitochondrial function by activating the mitochondrial membrane potential.These results suggest that EGT and ABX may have different molecular mechanisms of action, but both enhance GCase activity, improve autophagy-lysosome dynamics and mitochondrial functions.