bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation of the role of a lysine demyristoylase in adipose tissue‐myocardium crosstalk in cardiometabolic disease
Authors: Bagchi Rushita A. , Hu Tianjing , Major Jennifer L. , Cao Ji , Cavasin Maria A. , Mestroni Luisa , Lam Maggie P.Y. , Lin Hening , McKinsey Timothy A. 
Published: April 2020

Histone deacetylase 11 (HDAC11) is the lone class IV HDAC whose biological function is largely unexplored. Previously, we demonstrated that deletion of HDAC11 in vivo stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT) via a genomic mechanism dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl‐histone binding protein in brown adipocytes. Here, we hypothesize that HDAC11 inactivation primes the heart for protection from pathological remodeling consequent to diet‐induced obesity (DIO) via modulation of adipose tissue transcriptome and secretome (Figure
). Gene expression analysis showed that selective pharmacologic inhibition of HDAC11 promotes brown adipocyte formation and Ucp1 expression in vitro and in vivo. HDAC11‐deficient mice, in response to high‐fat feeding, exhibit attenuated obesity, insulin resistance, and hepatic steatosis, concomitant with increased levels of the circulating cardioprotective hormone adiponectin. Using histological analysis, atomic force microscopy and quantitative mass spectrometry, we demonstrate that adipose tissue lacking HDAC11 is protected from pathologic remodeling as a consequence of chronic high caloric diet administration. At the level of the heart, we demonstrate for the very first time that HDAC11 functions as a negative regulator of physiological hypertrophy. HDAC11‐deficient hearts exhibit attenuated hypertrophic gene expression after chronic high‐fat feeding. HDAC11 loss also protects cardiomyocytes from pathological hypertrophy and fetal gene activation induced by high fat serum. Using orthogonal click chemistry, fluorescence correlation spectroscopy and super‐resolution microscopy, we establish for the first time that HDAC11 exerts its non‐genomic action by modifying fatty acylation of a cytosolic scaffolding protein, AKAP12 (a.k.a. gravin) and regulation of β‐adrenergic receptor signaling (Figure
). These findings outline a novel and highly druggable pathway for the regulation of cardiometabolic disease at the level of adipose tissue and the heart, and suggest a potential for HDAC11‐selective inhibitors for the treatment of obesity and cardiometabolic disease.Support or Funding InformationThis work was supported by NIH (HL116848, HL127240, HL147558, DK119594) and the American Heart Association (16SFRN31400013) to T.A.M. R.A.B. (FRN‐216927) and J.L.M. (FRN‐395620) received funding from the Canadian Institutes of Health Research.Proposed model for HDAC11‐mediated cross‐talk between adipose tissue and the heart in cardiometabolic disease.Figure 1Schematic of the mechanism for HDAC11 modulation of AKAP12‐mediated βAR signaling.Figure 2
Identifying CoADR and Npsr Function: A Metagenomic Analysis of The Sulfur Reducing Capabilities of CoADR and Npsr
Authors: Wragan Max , Crane E.J. , Cavalcanti Andre , Spindler Archie 
Published: April 2020

Coenzyme‐A disulfide reductase (CoADR) and NADH‐dependent persulfide reductase (Npsr) are enzymes that have long been suspected to metabolize inorganic sulfur compounds due to their anaerobic environments in which they are found. Previous studies have had difficulty proving that CoADR and Npsr perform sulfur respiration through direct approach, which is why this research explored CoADR and Npsr’s relationship with sulfur reduction indirectly through metagenomic analysis. These results compiled the geochemistry, biochemistry, and microbiology of a wide variety of proteins with known functions and explored their relationship with CoADR and Npsr. Our data was compiled through the Joint Genome Institute’s metagenome database and run utilizing their BLAST program. This data was analyzed through Principle Component Analysis (PCA) which suggested CoADR and Npsr’s role as sulfur reducing enzymes via their correlation and alignment with other known sulfur reducing proteins, and their lack of their of with sulfate reducing, oxidative stress, and reversible sulfur cycling proteins.Support or Funding InformationFunding for research came from NSF grant to Dr. EJ Crane. Research was conducted at the Department of Molecular Biology, Pomona College, Claremont, CAContributors: Max Wragan, Archie Spindler, Dr. EJ Crane, and Dr. Andre CavalcantiPlots of the scores of each environment in the first two principal components. Aerobic environments are shown in teal and anaerobic environments are shown in orange. The 95% confidence ellipses are also shown for each category.Figure 1Variable PCA with grouping. Each arrow represents a protein. The color of each arrow corresponds to the predicted function of the protein. Dimensions 2 and 3 were utilized, rather than the default Dimensions 1 and 2, to increase clarity of figure. CoADR and Npsr were found to group among known Elemental Sulfur Reducing Proteins—PsrA, SudHa, and SudHb—suggesting CoADR and Npsr also act as elemental sulfur reducersFigure 2
Effects of a corn/bean‐based beverage on gastrointestinal symptoms in subjects with abdominal obesity
Authors: Gutiérrez-Salmeán Gabriela , Hernández-Ortega Marcela , Hernández-Hernández Cecilia , Ortega-Velázquez Sofía 
Published: April 2020

BackgroundInflammation underlying obesity has been linked to alterations in the gut‐brain axis, clinically manifesting, among others, as defects in intestinal motility thus gastrointestinal distress. Although diet therapy traditionally excludes foods with fermentable components such as corn and beans, it is proposed that some varieties of these have high contents of phytochemicals, such as polyphenols, capable of positively influencing symptomatology.ObjectiveTo assess the effect of a corn and bean‐based beverage on gastrointestinal symptoms in subjects with abdominal obesity.MethodsWe carried out a randomized placebo‐controlled clinical trial (CONBIOETICA approved) in which a beverage was given (supplement: chapalote (red) corn and ayocote (purple) beans, providing 100 mg EAG vs. placebo: white corn and beans) to subjects with abdominal obesity. Gastrointestinal symptoms, stool consistency and abdominal circumference, were assessed every two weeks, for 2 months. After determining the normality of data, an ANOVA for repeated measures with Tukey’s posthoc was performed for intragroup inferential analysis; the effects between treatments were compared with independent t‐Student. p<0.05 was considered as statistical significance.Results40 participants, mostly women, concluded the study. A statistically significant decrease in gastrointestinal symptoms was found in both groups over time; with no intergroup difference. In stool consistency, the supplement showed a statistically significant improvement. Both groups presented a significant decrease in abdominal circumference.ConclusionsCorn and beans may contain elements other than polyphenols that improve gastrointestinal symptoms, so their exclusion from the diet in patients referring irritable bowel traits must be reconsidered.Support or Funding InformationUniversidad Anáhuac México (institutional research fund)Changes in GI symptoms, stool consistency and abdominal circumference after 2‐month intervention.Figure 1
Hayeobtan ameliorates high fat/high cholesterol diet‐induced hypertriglyceridemia and endothelial dysfunction
Authors: Kim Hye Yoom , Hong Mi Hyeon , Na Se Won , Jang Youn Jae , Cho Kyoung Woo , Kang Dae Gill , Lee Ho Sub 
Published: April 2020

The leaves of lotus are called ‘Hayeob’ (
), which is known to have the effect of extinguishing heat, smoothing water metabolism, clearing the blood, and releasing blood(1–2). This experimental study was designed to investigate the inhibitory effects of Hayeobtan on lipid metabolism in high fat/cholesterol diet (HFCD)‐induced hypertriglyceridemia(3–4). Sprague Dawley rats were fed the HFCD diet with/without fluvastatin (Flu, positive control) 3 mg/kg/day, and HYT 100 or 200 mg/kg/day, respectively. All groups received a regular diet or HF diet, respectively, for 13 weeks. The last three groups treatment of Flu and HYT 100, and HYT200 orally for 9 weeks. Treatment of HYT markedly attenuated plasma levels of triglycerides and augmented plasma levels of high‐density lipoprotein (HDL) in HFCD‐fed rats. HYT and Flu also led to an increase in lipoprotein lipase activity in the HFCD group. On the other hand, HYT and Flu led to an decrease in fatty acid synthase and free fatty acid activity in the HFCD group. Treatment with HYT suppressed increased expressions of PPAR‐α and AMPK in HFCD rat liver or muscle. In addition, the HYT attenuated triglyceridemia by inhibition of PPAR‐γ and FABP protein expression levels and LXR and SREBP‐1 gene expression in liver or muscle. The HYT significantly prevented the development of the metabolic disturbances such as hypertriglyceridemia and hyperlipidemia. Taken together, the administration of HYT improves hypertriglyceridemia through the alteration in suppression of triglyceride synthesis and accentuated of triglyceride decomposition. These results suggested that HYT is useful in the prevention or treatment of hypertriglyceridemia‐related disorders such as triglyceride metabolism.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2017R1A5A2015805)(2019R1I1A3A01062432).
Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation
Authors: Trivedi Kavita K. , Bartash Rachel , Letourneau Alyssa R. , Abbo Lilian , Fleisher Jorge , Gagliardo Christina , Kelley Shannon , Nori Priya , Rieg Gunter K. , Silver Phyllis , Srinivasan Arjun , Vargas Jaclyn , Ostrowsky Belinda ,   the Partnership for Quality Care (PQC) Inpatient Antimicrobial Stewardship Working Group
Published: April 2020

Objectives:
To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities.

Design:
Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017.

Setting:
ICUs in 12 U.S. acute care hospitals with median bed size 563.

Patients:
Receiving antibiotics on participating units on March 1, 2017.

Interventions:
The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent.

Measurements and Main Results:
Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8–81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9–82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy.

Conclusions:
In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.
A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019(COVID-19)
Authors: Zhong Ming , Sun Aijun , Xiao Ting , Yao Ge , Sang Ling , Zheng Xia , Zhang Jinyan , Jin Xuejuan , Xu Lei , Yang Wenlong , Wang Peng , Hu Kai , Zhang Dingyu , Ge Junbo 
Published: April 2020

AbstractObjectTo evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19).MethodsA randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days.ResultNine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P=0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P=0.09).ConclusionIn our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19.
The latitudinal diversity gradient in brush-footed butterflies (Nymphalidae): conserved ancestral tropical niche but different continental histories
Authors: Chazot Nicolas , Condamine Fabien L. , Dudas Gytis , Peña Carlos , Matos-Maraví Pavel , Freitas Andre V. L. , Willmott Keith R. , Elias Marianne , Warren Andrew , Aduse-Poku Kwaku , Lohman David J. , Penz Carla M. , DeVries Phil , Kodandaramaiah Ullasa , Fric Zdenek F. , Nylin Soren , Müller Chris , Wheat Christopher , Kawahara Akito Y. , Silva-Brandão Karina L. , Lamas Gerardo , Zubek Anna , Ortiz-Acevedo Elena , Vila Roger , Vane-Wright Richard I , Mullen Sean P. , Jiggins Chris D. , Slamova Irena , Wahlberg Niklas 
Published: April 2020

AbstractThe latitudinal diversity gradient (LDG) is arguably one of the most striking patterns in nature. The global increase in species richness toward the tropics across continents and taxonomic groups stimulated the formulation of many hypotheses to explain the underlying mechanisms of this pattern. We evaluated several of these hypotheses to explain spatial diversity patterns in the butterfly family, Nymphalidae, by assessing the contributions of speciation, extinction, and dispersal to the LDG, and also the extent to which these processes differ among regions at the same latitude. We generated a new, time-calibrated phylogeny of Nymphalidae based on 10 gene fragments and containingca. 2,800 species (∼45% of extant diversity). Neither speciation nor extinction rate variations consistently explain the LDG among regions because temporal diversification dynamics differ greatly across longitude. For example, we found that Neotropical nymphalid diversity results from low extinction rates, not high speciation rates, and that biotic interchanges with other regions were rare. Southeast Asia was also characterized by a low speciation rate but, unlike the Neotropics, was the main source of dispersal events through time. Our results suggest that global climate change throughout the Cenozoic, particularly during the Eocene-Oligocene transition, combined with the conserved ancestral tropical niches, played a major role in generating the modern LDG of butterflies.
Development and Multicenter Performance Evaluation of The First Fully Automated SARS-CoV-2 IgM and IgG Immunoassays
Authors: Qian Chungen , Zhou Mi , Cheng Fangming , Lin Xiaotao , Gong Yijun , Xie Xiaobing , Li Ping , Li Zhiyong , Zhang Pingan , Liu Zejin , Hu Fang , Wang Yun , Li Quan , Zhu Yan , Duan Guikai , Xing Yinting , Song Huanyu , Xu Wenfang , Liu Bi-Feng , Xia Fuzhen 
Published: April 2020

AbstractBACKGROUNDThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid tests. However, there are many limitations of nucleic acid tests, including low throughput and high rates of false negatives. More sensitive and accurate tests to effectively identify infected patients are needed.METHODSThis study has developed fully automated chemiluminescent immunoassays (CLIA) to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients with diseases other than COVID-19, and 586 donors of a normal population. Clinical sensitivity was assessed on 503 confirmed cases of SARS-CoV-2 by RT-PCR and 52 suspected cases.RESULTSThe assays demonstrated satisfied assay precision with coefficient of variation (CV) of less than 4.45%. Inactivation of specimen does not affect assay measurement. SARS-CoV-2 IgM shows clinical specificity of 97.33% and 99.49% for hospitalized patients and normal population respectively. SARS-CoV-2 IgG shows clinical specificity of 97.43% and 99.15% for the hospitalized patients and the normal population respectively. SARS-CoV-2 IgM and IgG show clinical sensitivity of 85.88% and 96.62% respectively for confirmed SARS-Cov-2 infection with RT-PCR, of 73.08% and 86.54% respectively for suspected cases.CONCLUSIONSwe have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.
Survival-Convolution Models for Predicting COVID-19 Cases and Assessing Effects of Mitigation Strategies
Authors: Wang Qinxia , Xie Shanghong , Wang Yuanjia , Zeng Donglin 
Published: April 2020

SummaryCountries around the globe have implemented unprecedented measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic. We aim to predict COVID-19 disease course and compare effectiveness of mitigation measures across countries to inform policy decision making. We propose a robust and parsimonious survival-convolution model for predicting key statistics of COVID-19 epidemics (daily new cases). We account for transmission during a pre-symptomatic incubation period and use a time-varying effective reproduction number (Rt) to reflect the temporal trend of transmission and change in response to a public health intervention. We estimate the intervention effect on reducing the infection rate and quantify uncertainty by permutation. In China and South Korea, we predicted the entire disease epidemic using only data in the early phase (two to three weeks after the outbreak). A fast rate of decline in Rt was observed and adopting mitigation strategies early in the epidemic was effective in reducing the infection rate in these two countries. The lockdown in Italy did not further accelerate the speed at which the infection rate decreases. The effective reproduction number has staggered around Rt = 1.0 for more than 2 weeks before decreasing to below 1.0, and the epidemic in Italy is currently under control. In the US, Rt significantly decreased during a 2-week period after the declaration of national emergency, but afterwards the rate of decrease is substantially slower. If the trend continues after May 1, the first wave of COVID-19 may be controlled by July 26 (CI: July 9 to August 27). However, a loss of temporal effect on infection rate (e.g., due to relaxing mitigation measures after May 1) could lead to a long delay in controlling the epidemic (November 19 with less than 100 daily cases) and a total of more than 2 million cases.
Platelets exploit fibrillar adhesions to assemble fibronectin matrix revealing new force-regulated thrombus remodeling mechanisms
Authors: Lickert Sebastian , Selcuk Kateryna , Kenny Martin , Mehl Johanna L. , Früh Susanna M. , Burkhardt Melanie A. , Studt Jan-Dirk , Schoen Ingmar , Vogel Viola 
Published: April 2020

ABSTRACTUpon vascular injury, platelets are crucial for thrombus formation and contraction, but do they directly initiate early tissue repair processes? Using 3D super-resolution microscopy, micropost traction force microscopy, and specific integrin or myosin IIa inhibitors, we discovered here that platelets form fibrillar adhesions. They assemble fibronectin nanofibrils using αIIbβ3 (CD41/CD61, GPIIb-IIIa) rather than α5β1 integrins, in contrast to fibroblasts. Highly contractile platelets in contact with thrombus proteins (fibronectin, fibrin) pull fibronectin fibrils along their apical membrane, whereas platelets on basement membrane proteins (collagen IV, laminin) are less contractile generating less stretched planar meshworks beneath themselves. As probed by vinculin-decorated talin unfolding, platelets on fibronectin generate similar traction forces in apical fibrillar adhesions as fibroblasts do. These are novel mechanobiology mechanisms by which platelets spearhead the fibrillogenesis of the first de novo ECM, including its 2D versus 3D network architectures depending on their ECM environment, and thereby pave the way for cell infiltration.