bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: a meta-analysis
Authors: Simadibrata Daniel Martin , Calvin Julius , Wijaya Alya Darin , Ibrahim Naufal Arkan Abiyyu 
Published: September 2020

AbstractThe neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients, thus allowing early risk stratification. In this study, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients. A literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. The risk of bias was assessed using the Newcastle Ottawa Scale (NOS). A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI). Meta-regression analysis was done to identify potential confounders. A total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72-1.04; I2=75% and 1.68; 95%CI 0.98-2.39; I2=99%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.75 (95%CI 0.97-7.72). Meta-regression analysis showed that the association between NLR levels on admission and COVID-19 severity and mortality was unaffected by age (p=0.236; p=0.213, respectively). High NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.Key PointsHigh neutrophil-to-lymphocyte ratio (NLR) is associated with severe COVID-19 and mortalityNLR is a simple, accessible, near real-time, and cost-effective biomarker recommended for use in resource-limited healthcare settings
Elucidating the Joint Genetic Architecture of Mood Disorder and Schizophrenia
Authors: Lam Max , Thompson Meiling , Li Baijia , Edwards Alexis C. , Chen Chia-Yen , Ge Tian , Cai Na , Bigdeli Tim , Lencz Todd , Kendler Kenneth , Huang Hailiang 
Published: September 2020

AbstractIntroductionRecent advances in psychiatric genomics have enabled large-scale genome-wide scans that elucidated genetic architecture both in mood disorder and schizophrenia across individuals of East Asian and European descent. Investigating joint genetic architecture of these psychiatric traits enables the identification of common and diverging etiological mechanisms underlying these psychiatric illnesses. Here, we leverage on the largest GWAS of schizophrenia and mood disorder conducted to date in East Asian and European descent samples to elucidate the joint genetic architecture that underlie these psychiatric disorders.MethodologyWe carried out GWAS meta-analysis on both European (EUR) and East Asian (EAS) Ancestry summary statistics for Major Depressive Disorder (MDD) and Schizophrenia via Multi-Trait Analysis of GWAS. Downstream pathway, eQTL, chromatin interaction analysis were carried out to characterize genome-wide results. In addition we carried out genetic correlations and polygenic risk prediction analysis to further study the joint genetic architectures of mood disorder and schizophrenia.ResultsThere were 308 loci that was significantly associated with at least one trait. Specifically, there were 98 independent loci in EUR-MDD, 5 loci for MTAGx-EAS-MDD, 121 loci for MTAGx-EUR-MDD, 8 independent loci for EAS-SZ, 171 independent loci for EUR-SZ, 124 independent loci for MTAGx-EAS-SZ, and 159 independent loci for MTAGx-EUR-SZ. In all, 61 loci were novel across traits. SOAT1 and FOXO3 genes were implicated based on genome-wide associations. 114 gene(s) were implicated in eQTL analysis of gene expression in brain tissue. Gene-set analysis show support for GABA-egic pathways implicated in MDD, driven by several GABA-alpha receptor genes as well as more peripheral PLCL1 and NISCH genes that are responsible for endocytosis and neuronal trafficking. Cross-Ancestry genetic correlations ascertained that the CONVERGE MDD phenotype generally holds higher SNP based heritability and is likely driven by case-ascertainment procedures. Finally, polygenic risk score modelling indicates that MTAGx procedures were effective in enriching GWAS signals in the EAS-MDD for prediction in an independent case-control sample.DiscussionHere we are able to demonstrate that cross-trait cross-ancestry approaches in schizophrenia and MDD not only yields new discoveries to the genetic architecture of these illnesses; we were able to identify new biological underpinnings within the GABA pathways for depressive disorders. The evidence in the current report underscores the importance of taking into consideration both phenotype and ancestry complexities in genome-wide studies.
What is the Relationship Between Obesity and new Circadian Rhythm Parameters in Turkish Children and Adolescents? A Case-Control Study
Authors: Karadag Mehmet , Yilmaz Gulay Can 
Published: September 2020

AbstractAlthough the relationship between circadian rhythm parameters and obesity in children and adolescents are widely recognized, there are still not enough studies. The concept of Sleep Corrected Social Jet lag (SJLsc) has been formulated recently and its relationship with childhood obesity has not been established. In this study, we aimed to compare circadian rhythm parameters between obese and normal-weight children and adolescents. Seventy-nine obese and eighty-two normal-weighted children and adolescents aged between 8–17 years participated in this case-control study which took place in Turkey’s Mardin province. Sociodemographic information, Childhood Chronotype Questionnaire, and anthropometric data were collected. The average age of the obese and controls were 12.3 ± 2.3, 12.4±2.2 respectively. Obese young had more evening preference, sleep dept duration, SJL duration, SJLsc duration and morning Evening Scale (MeScale) scores; less mean sleep duration (p<0.005). In regression analyses, BMI z scores were significant correlated with all circadian rhythm parameters, except SJLsc duration, WC z scores were significant correlated with all circadian rhythm parameters, except mean sleep duration. After adjustment, the high mescale scores (OR:1.142, p<0.05) and the presence of a psychiatric disease in the mother (OR:15.075, p<0.05) were associated with obesity. Circadian rhythm parameters can play an important role in the etiology of obesity. Future studies with larger samples and fewer confounding factors are needed to clarify the etiological factors.
Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): a randomized controlled trial
Authors: Haq Kazi T. , Rogovoy Nichole M. , Thomas Jason A. , Hamilton Christopher , Lutz Katherine J. , Wirth Ashley , Bender Aron B. , German David M. , Przybylowicz Ryle , van Dam Peter , Dewland Thomas A. , Dalouk Khidir , Stecker Eric , Nazer Babak , Jessel Peter M. , MacMurdy Karen S. , Zarraga Ignatius Gerardo E. , Beitinjaneh Bassel , Henrikson Charles A. , Raitt Merritt , Fuss Cristina , Ferencik Maros , Tereshchenko Larisa G. 
Published: September 2020

AbstractIntroductionAdaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT; however, their effects on the electrical dyssynchrony have not been compared.MethodsWe conducted a double-blind, randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrodes body surface mapping. We measured electrical dyssynchrony on the epicardial surface using noninvasive electrocardiographic imaging (ECGI) before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times.ResultsWe randomized 27 participants (mean age 64±12 y; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 155±21 ms; strict left bundle branch block (LBBB) in 13%). In atypical LBBB (n=11;41%) with S-waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in those who met the strict LBBB criteria. As compared to baseline, VEU reduced post-CRT in aCRT (median reduction 18.9(interquartile range 4.3-29.2 ms; P=0.034), but not in conventional CRT (21.4(−30.0 to 49.9 ms; P=0.525) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups.ConclusionThe effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar. Further studies are needed to investigate if atypical LBBB with prominent S wave in V5-V6responds to His bundle pacing.
Experimental evidence that UV/yellow colouration functions as a signal of parental quality in the blue tit
Authors: García-Campa Jorge , Müller Wendt , Morales Judith 
Published: September 2020

AbstractIn bi-parental species, reproduction is not only a crucial life-history stage where individuals must take fitness-relevant decisions, but these decisions also need to be adjusted to the behavioural strategies of a partner. Hence, communication is required, which could be facilitated by condition-dependent signals of parental quality. Yet, these traits have (co-)evolved in multiple contexts within the family, as during reproduction different family members may coincide and interact at the site of breeding. In this study we explore whether a condition-dependent trait acts a quality signal and regulates intra-family interactions in a bird species, the blue tit (Cyanistes caeruleus). As a family is a complex network where signals could be perceived by multiple receivers, we expected that experimentally blocking the reflectance of an adult’s UV/yellow colouration of breast feathers may affect the behavioural strategies of all family members. We found an increase of parental investment in nests with an UV-blocked adult, as the partner compensated for the perceived lower rearing capacity. As the UV-blocked adult did not change its provisioning behaviour, as was to be expected, their partner must have responded to the (manipulated) signal but not to a behavioural change. However, offspring did not co-adjust their begging intensity to a signal of parental quality. Opposite to adults, we propose that offspring respond to the behaviour but not to the parental signal. Overall, our results show experimentally at the first time that UV/yellow colouration of blue tits acts as a quality signal revealing the rearing capacity to mates.
Hyaluronic Acid Fuels Pancreatic Cancer Growth
Authors: Kim Peter K. , Halbrook Christopher J. , Kerk Samuel A. , Wisner Stephanie , Kremer Daniel M. , Sajjakulnukit Peter , Hou Sean W. , Thurston Galloway , Anand Abhinav , Yan Liang , Salamanca-Cardona Lucia , Welling Samuel D. , Zhang Li , Pratt Matthew R. , Keshari Kayvan R. , Ying Haoqiang , Lyssiotis Costas A. 
Published: September 2020

AbstractRewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not impair tumor growth, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. Here, we show that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Furthermore, HA facilitates proliferation in nutrient-starved wild-type PDA. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles.
ASXL1 Directs Neutrophilic Differentiation via Modulation of MYC and RNA Polymerase II
Authors: Braun Theodore P. , Estabrook Joseph , Darmusey Lucie , Coleman Daniel J. , Schonrock Zachary , Smith Brittany M. , Taherinasab Akram , Enright Trevor , Coblentz Cody , Yashar William , Callahan Rowan , Mohammed Hisham , Druker Brian J. , Lusardi Theresa A. , Maxson Julia E. 
Published: September 2020

AbstractMutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. An epigenetic regulator, ASXL1 canonically directs the deposition of H3K27me3 via the polycomb repressive complex 2. However, its precise role in myeloid lineage maturation is incompletely described. We utilized single cell RNA sequencing (scRNA-seq) on a murine model of hematopoietic-specific ASXL1 deletion and identified a specific role for ASXL1 in terminal granulocyte maturation. Terminal maturation is accompanied by down regulation of Myc expression and cell cycle exit. ASXL1 deletion leads to hyperactivation of Myc in granulocyte precursors and a quantitative decrease in neutrophil production. This failure of normal developmentallyassociated Myc suppression is not accompanied by significant changes in the landscape of covalent histone modifications including H3K27me3. Examining the genome-wide localization of ASXL1 in myeloid progenitors revealed strong co-localization with RNA Polymerase II (RNAPII) at the promoters and spread across the gene bodies of transcriptionally active genes. ASXL1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription, consistent with the known role of ASXL1 as a mediator of RNAPII pause release. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator and highlighting a novel potential oncogenic mechanism for ASXL1 mutations in myeloid malignancies.
SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA
Authors: Jack Amanda , Ferro Luke S. , Trnka Michael J. , Wehri Eddie , Nadgir Amrut , Nguyenla Xammy , Costa Katelyn , Stanley Sarah , Schaletzky Julia , Yildiz Ahmet 
Published: September 2020

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes COVID-19, a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. Phase separation is driven, in part, by hydrophobic and electrostatic interactions. While the N protein forms spherical assemblies with unstructured RNA, it forms asymmetric condensates with viral RNA strands that contain secondary structure elements. Cross-linking mass spectrometry identified a region that forms interactions between N proteins in condensates, and truncation of this region disrupts phase separation. We also identified small molecules that alter the formation of N protein condensates. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.
Discovery of new antibacterial accramycins from a genetic variant of the soil bacterium,Streptomycessp. MA37
Authors: Maglangit Fleurdeliz , Zhang Yuting , Kyeremeh Kwaku , Deng Hai 
Published: September 2020

AbstractContinued mining of natural products from the strainStreptomycessp. MA37 in our laboratory led to the discovery of a minor specialised metabolite (SM) called accramycin A. Owing to its low yield (0.2mg/L) in the wild type strain, we investigated the roles of regulatory genes in the corresponding biosynthetic gene cluster (accBGC) through gene inactivation with the aim of improving the titre of this compound. One of the resulting mutants (ΔaccJ) dramatically upregulated the production of accramycin A1by 330-fold (66mg/L). Furthermore, ten new metabolites, accramycins B-K2-11, were discovered, together with two known compounds, naphthacemycin B112and fasamycin C13from the mutant extract. This suggested thataccJ, annotated as Multiple Antibiotic Resistance Regulator (MarR), is a negative regulator gene in the accramycin biosynthesis. Compounds1-13inhibited the Gram-positive pathogens (S. aureus, E. faecalis) and clinical isolates,E. faecium(K59-68 and K60-39), andS. haemolyticuswith minimal inhibitory concentration (MIC) values in the range of 1.5-12.5µg/mL. Remarkably, compounds1-13displayed superior activity against K60-39 (MIC = 3.1-6.3µg/mL) than ampicillin (MIC = 25µg/mL), and offer promising potential for the development of accramycin-based antibiotics that target multidrug-resistantEnterococcusclinical isolates. Our results highlight the importance of identifying the roles of regulatory genes in natural product discovery.
Ageratina adenophoraandLantana camarain Kailash Sacred Landscape, India: Current distribution and future climatic scenarios through modeling
Authors: Chaudhary Alka , Sarkar Mriganka Shekhar , Adhikari Bhupendra Singh , Rawat Gopal Singh 
Published: September 2020

AbstractThe Himalayan region is one of the global biodiversity hotspots. However, its biodiversity and ecosystems are threatened due to abiotic and biotic drivers. One of the major biotic threats to biodiversity in this region is the rapid spread of invasive alien species (IAS). Natural forests and grasslands are increasingly getting infested by IAS affecting regeneration of native species and decline in availability of bio-resources. Assessing the current status of IAS and prediction of their future spread would be vital for evolving specific species management interventions. Keeping this in view, we conducted an in-depth study on two IASs, viz.,Ageratina adenophoraandLantana camarain the Indian part of Kailash Sacred Landscape (KSL), Western Himalaya. Intensive field surveys were conducted to collect the presence ofA. adenophora(n= 567) andL. camara(n= 120) along an altitudinal gradient between 300 and 3000 m a.s.l. We performed Principle Component Analysis to nullify the multi-colinearity effects of the environmental predictors followingMaxEntspecies distribution model in the current and future climatic scenarios for both the species. All current and future model precision (i.e. Area Under the Curve; AUC) for both species was higher than 0.81. It is predicted that under the current rate of climate change and higher emission (i.e. RCP8.5 pathway),A. adenophorawill spread 45.3% more than its current distribution and is likely to reach up to 3029 m a.s.l. Whereas,L. camarawill spread 29.8% more than its current distribution range and likely to reach up to 3018 m a.s.l. Our results will help in future conservation planning and participatory management of forests and grasslands in the KSL– India.
Linking mountaintop removal mining to water quality for imperiled species using satellite data
Authors: Evans Michael J. , Kay Kathryn , Proctor Chelsea , Thomas Christian , Malcom Jacob W. 
Published: September 2020

AbstractEnvironmental laws need sound data to protect species and ecosystems. In 1996, a proliferation of mountaintop removal coal mines in a region home to over 50 federally protected species was approved under the Endangered Species Act. Although this type of mining can degrade terrestrial and aquatic habitats, the available data and tools limited the ability to analyze spatially extensive, aggregate effects of such a program. We used two large, public datasets to quantify the relationship between mountaintop removal coal mining and water quality measures important to the survival of imperiled species at a landscape scale across Kentucky, Tennessee, Virginia, and West Virginia. We combined an annual map of the extent of surface mines in this region from 1985 to 2015 generated from Landsat satellite imagery with public water quality data collected over the same time period from 4,260 monitoring stations within the same area. The water quality data show that chronic and acute thresholds for levels of aluminum, arsenic, cadmium, conductivity, copper, lead, manganese, mercury, pH, selenium, and zinc safe for aquatic life were exceeded thousands of times between 1985 and 2015 in streams that are important to the survival and recovery of species on the Endangered Species List. Linear mixed models showed that levels of manganese, sulfate, sulfur, total dissolved solids, total suspended solids, and zinc increased by 6.73E+01 to 6.87E+05 µg/L and conductivity by 3.30E+06 µS /cm for one percent increase in the mined proportion of the area draining into a monitoring station. The proportion of a drainage area that was mined also increased the likelihood that chronic thresholds for copper, lead, and zinc required to sustain aquatic life were exceeded. Finally, the proportion of a watershed that was mined was positively related to the likelihood that a waterway would be designated as impaired under the Clean Water Act. Together these results demonstrate that the extent of mountaintop removal mining, which can be derived from public satellite data, is predictive of water quality measures important to imperiled species - effects that must be considered under environmental law. These findings and the public data used in our analyses are pertinent to ongoing re-evaluations of the effects of current mine permitting regulations to the recovery and survival of federally protected species.