bluuebunny/crossref_metadata_2025_split huggingface dataset:
Top End Pulmonary Hypertension Study: Understanding Epidemiology, Therapeutic Gaps and Prognosis in Remote Australian Setting
Authors: Naing Pyi , Playford David , Strange Geoff , Abeyaratne Asanga , Berhane Thomas , Jospeph Sanjay , Costelloe Ellie , Hall Maddison , Scalia Gregory M , Forrester Douglas L , Falhammar Henrik , Kangaharan Nadarajah 
Published: September 2020

AbstractIntroductionThe Top End of Australia has a high proportion of Indigenous people with a high burden of chronic cardiac and pulmonary diseases likely to contribute to pulmonary hypertension (PH). The epidemiology of PH has not been previously studied in this region.MethodsPatients with PH were identified from the Northern Territory echocardiography database from January 2010 to December 2015 and followed to the end of 2019 or death. PH was defined as a tricuspid regurgitation velocity ≥2.75 m/s measured by Doppler echocardiography. The etiology of PH, as categorized by published guidelines, was determined by reviewing electronic health records.Results1764 patients were identified comprising 49% males and 45% Indigenous people. The prevalence of PH was 955 per 100,000 population (with corresponding prevalence of 1587 for Indigenous people). Hypertension, atrial fibrillation, diabetes and respiratory disease were present in 85%, 45%, 41% and 39%, respectively. Left heart disease was the leading cause for PH (58%), the majority suffering from valvular disease (predominantly rheumatic). Pulmonary arterial hypertension (PAH), respiratory disease related PH, chronic thromboembolic PH (CTEPH) and unclear multifactorial PH represented 4%, 16%, 2% and 3%, respectively. Underlying causes were not identifiable in 17% of the patients. Only 31% of potentially eligible patients were on PAH-specific therapy. At census, there was 40% mortality, with major predictors being age, ePASP and Indigenous ethnicity.ConclusionPH is prevalent in Northern Australia, with a high frequency of modifiable risk factors and other treatable conditions. Whether earlier diagnosis, interpretation and intervention improves outcomes merits further assessment.
Quantifying the Effects of Social Distancing on the Spread of COVID-19
Authors: Daghriri Talal , Ozmen Ozlem 
Published: September 2020

AbstractThis paper studies the interplay between the social distancing and the spread of COVID-19 disease—a widely spread pandemic that has affected nearly most of the world population. Starting in China, the virus has reached the United States of America with devastating consequences. Other countries severely affected by the pandemic are Brazil, Russia, United Kingdom, Spain, India, Italy, and France. Even though it is not possible to eliminate the spread of the virus from the world or any other country, it might be possible to reduce its effect by decreasing the number of infected people. Implementing such policies needs a good understanding of the system’s dynamics, generally not possible with mathematical linear equations or Monte Carlo methods because human society is a complex adaptive system with complex and continuous feedback loops. As a result, we use agent-based methods to conduct our study. Moreover, recent agent-based modeling studies for the COVID-19 pandemic show significant promise assisting decision-makers in managing the crisis through applying some policies such as social distancing, disease testing, contact tracing, home isolation, providing good emergency and hospitalization strategies, and preventing traveling would lead to reducing the infection rates. Based on imperial college modeling studies that prove increasing levels of interventions could slow down the spread of disease and infection cases as much as possible, and taking into account that social distancing policy is considered to be the most important factor that was recommended to follow. Our proposed model is designed to test if increasing the social distancing policies strictness can slow down the spread of disease significantly or not, and find out what is the required safe level of social distancing. So, the model was run six times, with six different percentages of social distancing with keeping the other parameters levels fixed for all experiments. The results of our study show that social distancing affects the spread of COVID-19 significantly, where the spread of disease and infection rates decrease once social distancing procedures are implemented at higher levels. Also, the behavior space tool was used to run ten experiments with different levels of social distancing, which supported the previous results. We concluded that applying and increasing social distancing policy levels led to significantly reduced infection rates, which result in decreasing deaths. Both types of experiments prove that infection rates are reduced dramatically when the level of social distancing intervention is implemented between 80% to 100%.
Extracorporeal Shockwave Therapy Versus Ultrasound Therapy for Plantar Fasciitis: Systematic Review and Meta-Analysis
Authors: Al-Siyabi Zeyana , Karam Mohammad , Al-Hajri Ethar , Alsaif Abdulmalik 
Published: September 2020

AbstractObjectiveTo compare the outcomes of Extracorporeal Shockwave Therapy (ESWT) versus Ultrasound Therapy (UST) in plantar fasciitis.MethodsA systematic review and meta-analysis were performed. An electronic search identifying studies comparing ESWT and UST for plantar fasciitis was conducted. Primary outcomes were morning and activity pain, functional impairment and the American Orthopaedic Foot and Ankle Society (AOFAS) scale score. Secondary outcomes included fascial thickness, primary efficacy success rate, activity limitations, pain intensity and satisfaction.ResultsSeven studies enrolling 369 patients were identified. No significant difference was found between ESWT and UST for functional impairment (Mean Difference [MD]= -2.90, P= 0.22), AOFAS scale score (MD= 35, P= 0.20) and pain in the first steps in the morning (MD= -4.72, P= 0.39). However, there was a significant improvement in pain during activity for the ESWT group (MD= -1.36, P= 0.005). For secondary outcomes, ESWT had improved results in terms of primary efficacy success rate, activity limitations and patient satisfaction. Reduction of planter fascia thickness showed no significant difference. Pain intensity after treatment had varied results amongst included studies.ConclusionESWT is superior to UST for plantar fasciitis as it improves pain activity and intensity, primary efficacy success rate and activity limitations.
Early blood transcriptomic markers of necrotizing enterocolitis in preterm pigs
Authors: Pan Xiaoyu , Muk Tik , Ren Shuqiang , Gao Fei , Sangild Per 
Published: September 2020

AbstractPreterm infants frequently develop necrotizing enterocolitis (NEC), a severe intestinal disorder associated with high mortality. Early detection of NEC is difficult due to poor specificity and sensitivity of clinical signs. We hypothesized that early development of NEC, before clear clinical symptoms appear, might affect expression of blood genes, potentially related to early systemic immune responses. Using preterm pigs as models for preterm infants, a retrospective analysis was performed on 129 infant formula fed pigs that had NEC diagnosis at necropsy on day 5. Clinical data including growth, activity, hematology, gastric residuals, incidence of diarrhea, bloody stool and abdominal distention were retrospectively reviewed. During this early postnatal period, except that bloody stool was observed in 19% of NEC pigs and absent in healthy pigs, no other clinical outcomes showed difference between NEC and healthy pigs. Whole blood transcriptome was compared between NEC pigs (NEC, n=20) and their litter-mate healthy controls (CON, n=19) on day 5, and revealed 344 differentially expressed genes (DEGs). PubMed literature search identified 123 genes that co-occurred with at least one of 9 NEC-related keywords (NEC, colitis, necrotic, hemorrhage, epithelial apoptosis, intestinal inflammation, inflammatory bowel disease, Crohn’s disease, ulcerative colitis). Co-expression network analysis suggested PAK2 as one of the hub genes. Using whole blood and dried blood spots (DBS) from another group of preterm pigs for validation, up-regulation of PAK2 and genes that co-occurred with NEC and other keywords in PubMed literatures (AOAH, ARG2, FKBP5 and STAT3) was confirmed in severe NEC cases. Specifically,ex vivostimulation of cord blood withS.epidermidisincreased ARG2. Our results show that whole blood gene expressions are affected in preterm pigs at an early stage when NEC is suspicious. Expression of target genes may be used to indicate NEC severity and associated bacterial infection. Routinely collected neonatal DBS may be used to develop early biomarkers for identifying infants with severe NEC lesions, thus providing better intervention strategy.
A new species of subgenusTyphlodromus(Anthoseius) De Leon (Acari: Phytoseiidae), and phytoseiid mites intercepted in samples imported from 12 different countries to Taiwan
Authors: Liao Jhih-Rong , Ho Chyi-Chen , Ko Chiun-Cheng 
Published: September 2020

AbstractGlobal trade has increased the invasion risk of exotic organisms and damaged agricultural and natural ecosystems. The Bureau of Animal and Plant Health Inspection and Quarantine (BAPHIQ) handles quarantine services of animal- and plant-associated pests and diseases in Taiwan. The predatory mite family Phytoseiidae (Acari: Mesostigmata) is a well-known group due to the potential use of certain species as biocontrol agents for small phytophagous pests. Some species are available in commercial markets and frequently used in biological control in many agricultural systems especially in greenhouse crops. However, exotic biological control agents may interfere with native or naturalized populations of predatory mites and they may threaten indigenous populations via intraguild predation. The present study aims to provide the phytoseiid mite species found in plant quarantine from 2006–2013. Twenty-five species belonging two subfamilies and eight genera were found in samples imported to Tawan from twelve countries, including one new speciesTyphlodromus(Anthoseius)ueckermannisp. nov.from South Africa. The checklist provides distribution, remarks, and also an identification key for all species.
Experimental and computational studies on molecular mechanism by which Curcumin allosterically inhibits Dengue protease
Authors: Lim Liangzhong , Dang Mei , Roy Amrita , Kang Jian , Song Jianxing 
Published: September 2020

ABSTRACTFlaviviruses including DENV and ZIKV encode a unique two-component NS2B-NS3 protease essential for maturation/infectivity, thus representing a key target for designing anti-flavivirus drugs. Here for the first time, by NMR and molecular docking, we reveal that Curcumin allosterically inhibits the Dengue protease by binding to a cavity with no overlap with the active site. Further molecular dynamics (MD) simulations decode that the binding of Curcumin leads to unfolding/displacing the characteristic β-hairpin of the C-terminal NS2B and consequently disrupting the closed (active) conformation of the protease. Our study identified a cavity most likely conserved in all flaviviral NS2B-NS3 proteases, which could thus serve as a therapeutic target for discovery/design of small molecule allosteric inhibitors. Moreover, as Curcumin has been used as a food additive for thousands of years in many counties, it can be directly utilized to fight the flaviviral infections and as a promising starting for further design of potent allosteric inhibitors.
Robust differentiation of human enteroendocrine cells from intestinal stem cells
Authors: Zeve Daniel , Stas Eric , de Sousa Casal Joshua , Mannam Prabhath , Qi Wanshu , Yin Xiaolei , Dubois Sarah , Shah Manasvi S. , Syverson Erin P. , Hafner Sophie , Karp Jeffrey M. , Carlone Diana L. , Ordovas-Montanes Jose , Breault David T. 
Published: September 2020

ABSTRACTEnteroendocrine (EE) cells are the most abundant hormone-producing cells in humans and are critical regulators of energy homeostasis and gastrointestinal function. Challenges in converting human intestinal stem cells (ISCs) into functional EE cells,ex vivo, have limited progress in elucidating their role in disease pathogenesis and in harnessing their therapeutic potential. To address this, we employed small molecule targeting of the endocannabinoid receptor signaling pathway, JNK and FOXO1, known to mediate endodermal development and/or hormone production, together with directed differentiation of human ISCs from the duodenum and rectum. We observed marked induction of EE cell differentiation and gut-derived expression and secretion of SST, 5HT, GIP, CCK, GLP-1 and PYY upon treatment with various combinations of three small molecules: rimonabant, SP600125 and AS1842856. Robust differentiation strategies capable of driving human EE cell differentiation is a critical step towards understanding these essential cells and the development of cell-based therapeutics.
Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels
Authors: Kondapuram Mahesh , Frieg Benedikt , Yüksel Sezin , Schwabe Tina , Sattler Christian , Lelle Marco , Schweinitz Andrea , Schmauder Ralf , Benndorf Klaus , Gohlke Holger , Kusch Jana 
Published: September 2020

ABSTRACTHyperpolarization-activated and cyclic nucleotide (HCN) modulated channels are tetrameric cation channels. In each of the four subunits, the intracellular cyclic nucleotide-binding domain (CNBD) is coupled to the transmembrane domain via a helical structure, the C-linker. High-resolution channel structures suggest that the C-linker enables functionally relevant interactions with the opposite subunit, which might be critical for coupling the conformational changes in the CNBD to the channel pore. We combined mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations to show that residue K464 of the C-linker is essential for stabilizing the closed state of the mHCN2 channel by forming interactions with the opposite subunit. MD simulations revealed that both cAMP and K464E induce a rotation of the intracellular domain relative to the channel pore, weakening the autoinhibitory effect of the unoccupied CL-CNBD region. The adopted poses are in excellent agreement with structural results.
Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish
Authors: García-Jaramillo Manuel , Beaver Laura M. , Truong Lisa , Axton Elizabeth R. , Keller Rosa M. , Prater Mary C. , Magnusson Kathy R. , Tanguay Robyn L. , Stevens Jan F. , Hord Norman G. 
Published: September 2020

AbstractIntroductionDietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. Here we tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We also explored the extent to which nitrate and nitrite treatment affected the brain metabolome in order to understand how nitrate and nitrite supplementation may affect indices of cognitive function.MethodsFish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2-4 weeks and free swim, startle response, innate predator avoidance, social cohesion, and shuttle box assays were performed.ResultsNitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment significantly increased anxiety-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted LC-MS/MS analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. An untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment including an 18-19% reduction in the neurotransmitter γ-aminobutyric acid (GABA), and 17-22% reduction in its precursor, glutamine, which may contribute to the increased anxiety-like behavior.ConclusionNitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health but was associated with mild anxiety-like behavior, changes in the brain metabolome, and caused a short-term decrease in executive function or associative learning.
The genetic status of IDH1/2 and EGFR dictates the vascular landscape and the progression of gliomas
Authors: Segura-Collar Berta , Garranzo-Asensio María , Herranz Beatriz , Hernández-SanMiguel Esther , Casas Bárbara. S. , Matheu Ander , Pérez-Núñez Ángel , Sepúlveda-Sánchez Juan M. , Hernández-Laín Aurelio , Palma Verónica , Gargini Ricardo , Sánchez-Gómez Pilar 
Published: September 2020

AbstractRationaleGlioma progression is driven by the induction of vascular alterations but how the tumor genotype influence these changes is still a pending issue. We propose to study the underlying mechanisms by which the genetic changes in isocitrate dehydrogenase 1/2 (IDH1/2) and epidermal growth factor receptor (EGFR) genes establish the different vascular profiles of gliomas.MethodsWe stratified gliomas based on the genetic status of IDH1/2 and EGFR genes. For that we used in silico data and a cohort of 93 glioma patients, where we analyzed the expression of several transcripts and proteins. For the in vitro and in vivo studies, we used a battery of primary glioblastoma cells derived from patients, as well as novel murine glioma cell lines expressing wild-type or mutant EGFR. In these models, the effect of the small molecule ibrutinib or the downregulation of CD248 and SOX9 was evaluated to establish a molecular mechanism.ResultsWe show that IDH1/2 mutations associate with a normalized vasculature. By contrast, EGFR mutations stimulate the plasticity of glioma cells and their capacity to function as pericytes in a bone-marrow and X-linked (BMX)/SOX9 dependent manner. The presence of tumor-derived pericytes stabilize the profuse vasculature and confers a growth advantage to these tumors, although they render them sensitive to pericyte-targeted molecules. Wild-type/amplified EGFR gliomas are enriched in blood vessels too, but they show a highly disrupted blood-brain-barrier due to a decreased BMX/SOX9 activation and pericyte coverage. This leads to poor nutrient supply, necrosis and hypoxia.ConclusionsThe function of tumor-derived pericytes delimitates two distinct and aggressive vascular phenotypes in IDH1/2 wild-type gliomas. Our results lay the foundations for a vascular dependent stratification of gliomas and suggest different therapeutic vulnerabilities depending on the genetic status of EGFR.Graphical Abstract. Schematic view of IDH and EGFR function in the regulation of glioma microenvironment.Mutant IDH gliomas express low levels of angiogenic molecules and have a vasculature reminiscent of normal tissue. EGFR mutations drive glioma growth by promoting tumor-to-pericyte transdifferentiation and vascular stabilization in a BMX-SOX9 dependent way. Leaky vessels with hypoxia and necrosis characterize tumors overexpressing the wild-type isoform of the receptor. These phenotypes determine the response to therapy of the different IDH wild-type gliomas.
Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease
Authors: Dolan Mary E. , Hill David P. , Mukherjee Gaurab , McAndrews Monica S. , Chesler Elissa J. , Blake Judith A. 
Published: September 2020

AbstractThe emergence of the SARS-CoV-2 virus and subsequent COVID-19 pandemic initiated intense research into the mechanisms of action for this virus. It was quickly noted that COVID-19 presents more seriously in conjunction with other human disease conditions such as hypertension, diabetes, and lung diseases. We conducted a bioinformatics analysis of COVID-19 comorbidity-associated gene sets, identifying genes and pathways shared among the comorbidities, and evaluated current knowledge about these genes and pathways as related to current information about SARS-CoV-2 infection. We performed our analysis using GeneWeaver (GW), Reactome, and several biomedical ontologies to represent and compare common COVID-19 comorbidities. Phenotypic analysis of shared genes revealed significant enrichment for immune system phenotypes and for cardiovascular-related phenotypes, which might point to alleles and phenotypes in mouse models that could be evaluated for clues to COVID-19 severity. Through pathway analysis, we identified enriched pathways shared by comorbidity datasets and datasets associated with SARS-CoV-2 infection.
Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection
Authors: Graham Jessica B. , Swarts Jessica L. , Leist Sarah R. , Schäfer Alexandra , Menachery Vineet D. , Gralinski Lisa E. , Jeng Sophia , Miller Darla R. , Mooney Michael A. , McWeeney Shannon K. , Ferris Martin T. , de Villena Fernando Pardo-Manuel , Heise Mark T. , Baric Ralph S. , Lund Jennifer M. 
Published: September 2020

AbstractThe COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.SummaryWe used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.