bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystatin C and Sarcopenia Predict Acute on Chronic Liver Failure Development and Mortality in Patients on the Liver Transplant Waiting List
Authors: Mauro Ezequiel , Crespo Gonzalo , Martinez-Garmendia Agustina , Gutierrez-Acevedo María Nelly , Diaz Juan Manuel , Saidman Julia , Bermudez Carla , Ortiz-Patron Jorge , Garcia-Olveira Lucrecia , Zalazar Fernanda , Narvaez Adrían , Spina Juan Carlos , Orta Ramiro , Savluk Lorena , Piano Salvatore , Marciano Sebastián , Gadano Adrían 
Published: March 2020

Background.
Cystatin C (CysC) is an early biomarker of renal dysfunction scarcely studied in patients awaiting liver transplantation (LT). Sarcopenia is frequent in cirrhosis and impacts prognosis. We aimed to assess the capability of these factors to predict survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT outcomes.

Methods.
Single-center study that included all cirrhotic patients listed for LT between 2014 and 2017. Competing risk regression analysis was used to evaluate the capability of liver-, kidney-, and global status-related variables at waitlist (WL) inclusion to predict WL mortality and ACLF. Variables associated with post-LT outcomes were evaluated with logistic regression analysis.

Results.
One-hundred-and-eighty patients were included. Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died. In the adjusted competing risk regression analysis, CysC ≥ 1.5 mg/L, sarcopenia and MELD-Na were independent predictors of ACLF in the WL, while CysC ≥ 1.5 mg/L, sarcopenia and albumin were independent predictors of mortality. The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in patients with sarcopenia and CysC ≥1.5 mg/L. An estimated glomerular filtration rate by chronic kidney disease (CKD)-EPI-CysC-creatinine <60 mL/min/1.73 m2 at WL inclusion was an independent predictor of the need for renal replacement therapy (RRT) in the first month post-LT.

Conclusions.
Higher levels of CysC and sarcopenia are strongly associated with the ACLF and mortality in WL. The assessment of both risk factors may improve the prognostic evaluation and allow identifying a group of patients with a very high risk of poor outcomes while awaiting LT.
Cocaine Use and Levamisole-Induced Vasculitis
Authors: Engels Dawn 
Published: March 2020

BACKGROUND:
Levamisole is an immunomodulatory medication previously used to treat rheumatoid arthritis and some types of cancers; it was banned for use in humans in 2000 owing to its harmful side effects. Use of levamisole-laced cocaine is associated with a life-threatening syndrome characterized by a necrotizing purpuric rash leading to tissue destruction and necrotic wounds. This Clinical Challenges article summarizes our experience with the care of 2 adult women diagnosed with levamisole-related vasculitis.

CASE:
Case 1 is a 46-year-old woman who presented with joint pain in her hands and legs, along with bilateral ear pain, swelling, and bleeding. She was initially diagnosed with vasculitis and possible systemic lupus erythematosus. She experienced multiple recurrences and exacerbation of her condition over a period of months. She was ultimately diagnosed with levamisole-related vasculitis from recurrent cocaine use resulting in bilateral above the knee amputations. The second case is a 50-year-old woman who presented to our emergency department with redness and swelling of her bilateral lower extremities. She developed blisters and pustules that rapidly evolved into abscesses and red lesions over the course of several months. Her wounds also deteriorated despite topical therapy that occurred in a context of recurring use of cocaine.

CONCLUSIONS:
Our experience with these cases suggests that WOC nurses should consider levamisole-induced vasculitis in all patients presenting with unexplained vasculitis-type lesions, and particularly when these lesions occur in the context of known or suspected use of illicit substances such as cocaine. Given the absence of clinical guidelines for this increasingly prevalent condition, we recommend wound care based on principles of moist wound healing, combined with judicious use of therapies with antimicrobial activity and nonadherent dressings to reduce pain. Finally, we strongly recommend that care of these patients occurs as one part of a multidisciplinary care approach that focuses on cessation of the use of cocaine and all other illicit substances.
Evolving Epidemiology and Impact of Non-pharmaceutical Interventions on the Outbreak of Coronavirus Disease 2019 in Wuhan, China
Authors: Wang Chaolong , Liu Li , Hao Xingjie , Guo Huan , Wang Qi , Huang Jiao , He Na , Yu Hongjie , Lin Xihong , Pan An , Wei Sheng , Wu Tangchun 
Published: March 2020

ABSTRACTBACKGROUNDWe described the epidemiological features of the coronavirus disease 2019 (Covid-19) outbreak, and evaluated the impact of non-pharmaceutical interventions on the epidemic in Wuhan, China.METHODSIndividual-level data on 25,961 laboratory-confirmed Covid-19 cases reported through February 18, 2020 were extracted from the municipal Notifiable Disease Report System. Based on key events and interventions, we divided the epidemic into four periods: before January 11, January 11-22, January 23 - February 1, and February 2-18. We compared epidemiological characteristics across periods and different demographic groups. We developed a susceptible-exposed-infectious-recovered model to study the epidemic and evaluate the impact of interventions.RESULTSThe median age of the cases was 57 years and 50.3% were women. The attack rate peaked in the third period and substantially declined afterwards across geographic regions, sex and age groups, except for children (age <20) whose attack rate continued to increase. Healthcare workers and elderly people had higher attack rates and severity risk increased with age. The effective reproductive number dropped from 3.86 (95% credible interval 3.74 to 3.97) before interventions to 0.32 (0.28 to 0.37) post interventions. The interventions were estimated to prevent 94.5% (93.7 to 95.2%) infections till February 18. We found that at least 59% of infected cases were unascertained in Wuhan, potentially including asymptomatic and mild-symptomatic cases.CONCLUSIONSConsiderable countermeasures have effectively controlled the Covid-19 outbreak in Wuhan. Special efforts are needed to protect vulnerable populations, including healthcare workers, elderly and children. Estimation of unascertained cases has important implications on continuing surveillance and interventions.
Endosymbiotic Rickettsiella causes cytoplasmic incompatibility in a spider host
Authors: Rosenwald Laura C. , Sitvarin Michael I. , White Jennifer A. 
Published: March 2020

AbstractMany arthropod hosts are infected with bacterial endosymbionts that manipulate host reproduction, but few bacterial taxa have been shown to cause such manipulations. Here we show that a bacterial strain in the genus Rickettsiella causes cytoplasmic incompatibility (CI) between infected and uninfected hosts. We first surveyed the bacterial community of the agricultural spider Mermessus fradeorum (Linyphiidae) using high throughput sequencing and found that individual spiders can be infected with up to five different strains of maternally-inherited symbiont from the genera Wolbachia, Rickettsia, and Rickettsiella. The Rickettsiella strain was pervasive, found in all 23 tested spider matrilines. We used antibiotic curing to generate uninfected matrilines that we reciprocally crossed with individuals infected only with Rickettsiella. We found that only 13% of eggs hatched when uninfected females were mated with Rickettsiella-infected males; in contrast, at least 83% of eggs hatched in the other cross types. This is the first documentation of Rickettsiella, or any Gammaproteobacteria, causing CI. We speculate that induction of CI may be much more widespread among maternally-inherited bacteria than previously appreciated. Further, our results reinforce the importance of thoroughly characterizing and assessing the inherited microbiome before attributing observed host phenotypes to well-characterized symbionts such as Wolbachia.
Assessing the Heterogeneity of Cardiac Non-myocytes and the Effect of Cell Culture with Integrative Single Cell Analysis
Authors: Iskra Brian S. , Davis Logan , Miller Henry E. , Chiu Yu-Chiao , Bishop Alexander R. , Chen Yidong , Aune Gregory J. 
Published: March 2020

AbstractCardiac non-myocytes comprise a diverse and crucial cell population in the heart that plays dynamic roles in cardiac wound healing and growth. Non-myocytes broadly fall into four cell types: endothelium, fibroblasts, leukocytes, and pericytes. Here we characterize the diversity of the non-myocytesin vivoandin vitrousing mass cytometry. By leveraging single-cell RNA sequencing we inform the design of a mass cytometry panel. To aid in annotation of the mass cytometry datasets, we utilize data integration with a neural network. We introduce approximately 460,000∼ single cell proteomes of non-myocytes as well as 5,000∼ CD31 negative single cell transcriptomes. Using our data, as well as previously reported datasets, we characterize cardiac non-myocytes with high depth in six mice, characterizing novel surface markers (CD9, CD200, Notch3, and FolR2). Further, we find that extended cell culture promotes the proliferation of CD45+CD11b+FolR2+IAIE- myeloid cells in addition to fibroblasts.
Bacteroides uniformis enhances endurance exercise performance through gluconeogenesis
Authors: Morita Hiroto , Kano Chie , Ishii Chiharu , Kagata Noriko , Ishikawa Takamasa , Uchiyama Yoshihide , Hara Susumu , Nakamura Teppei , Fukuda Shinji 
Published: March 2020

ABSTRACTAthletes require high levels of energy to exercise under extreme conditions. Gut microbiota supplies energy to the host; however, the mechanism how gut microbiota contribute in the athlete is unclear. In this study, we determined that gut microbiota of Japanese long-distance runners differed from that of non-athletes, and the Bacteroides uniformis cell number in the feces correlated with 3,000-m race time. Mice administrated with B. unformis extended the swimming time to exhaustion. Furthermore, acetate and propionate concentrations in the cecum increased in B. uniformis-administered mice subjected to weekly exercise. Expression levels of carnitine palmitoyl transferase la and phosphoenolpyruvate carboxykinase genes were elevated in the liver, suggesting that acetate and propionate produced by B. uniformis improve endurance exercise performance, at least in part, through enhancing gluconeogenesis. In addition, α-cyclodextrin administration increased B. uniformis and improved the performance in humans and mice, thus it is a candidate substance enhancing exercise performance through modification of gut microbiota.
Anti-inflammatory role of GM1 and modulatory effects of gangliosides on microglia functions
Authors: Galleguillos Danny , Wang Qian , Steinberg Noam , Shrivastava Gaurav , Dhami Kamaldeep , Rubinstein Karin , Giuliani Fabrizio , Churchward Matthew , Power Christopher , Todd Kathryn , Sipione Simonetta 
Published: March 2020

ABSTRACTGangliosides are sialic acid-containing glycosphingolipids highly enriched in the brain. Located mainly at the plasma membrane, gangliosides play important roles in signaling and cell-to-cell communication. Lack of gangliosides causes severe early onset neurodegenerative disorders, while more subtle deficits have been reported in Parkinson’s disease and in Huntington’s disease, two misfolded protein diseases with a neuroinflammatory component. On the other hand, administration of ganglioside GM1 provides neuroprotection in both diseases and in several other models of neuronal insult. While most studies have focused on the role of endogenous gangliosides and the effects of exogenously administered GM1 in neurons, their contribution to microglia functions that are affected in neurodegenerative conditions is largely unexplored. Microglia are the immune cells of the brain and play important homeostatic functions in health and disease. In this study, we show that administration of exogenous GM1 exerts a potent anti-inflammatory effect on microglia activated with LPS, IL-1β or upon phagocytosis of latex beads. These effects are partially reproduced by L-t-PDMP, a compound that stimulates the activity of the ganglioside biosynthetic pathway, while inhibition of ganglioside synthesis with GENZ-123346 increases microglial transcriptional response to LPS. We further show that administration of GM1 increases the uptake of apoptotic bodies and latex beads by microglia, as well as microglia migration and chemotaxis in response to ATP. On the contrary, decreasing microglial ganglioside levels results in a partial impairment in both microglial activities. Finally, increasing cellular ganglioside levels results in decreased expression and secretion of microglial brain derived neurotrophic factor (BDNF). Altogether, our data suggest that gangliosides are important modulators of microglia functions that are crucial to healthy brain homeostasis, and reveal that administration of ganglioside GM1 exerts an important anti-inflammatory activity that could be exploited therapeutically.
Systematic genome-wide querying of coding and non-coding functional elements inE. coliusing CRISPRi
Authors: Rishi Harneet S. , Toro Esteban , Liu Honglei , Wang Xiaowo , Qi Lei S. , Arkin Adam P. 
Published: March 2020

ABSTRACTGenome-wide repression screens using CRISPR interference (CRISPRi) have enabled the high-throughput identification of essential genes in bacteria. However, there is a lack of functional studies leveraging CRISPRi to systematically explore targeting of both the coding and non-coding genome in bacteria. Here we perform CRISPRi screens inEscherichia coliMG1655 K-12 targeting ~13,000 genomic features, including nearly all protein-coding genes, non-coding RNAs, promoters, and transcription factor binding sites (TFBSs) using a ~33,000-member sgRNA library, which represents the most compact and comprehensive genome-wide CRISPRi library inE. colito date. Our data reveal insights into the conditional essentiality of the genome with key refinements to screen design and profiling. First, we demonstrate that strong fitness defects associated with essential cellular processes can be resolved using inducible time-series measurements. We show that knockdowns of different classes of genes exhibit distinct, transient responses that are correlated to gene function with genes involved in translation exhibiting the strongest responses. We also query feature essentiality across several biochemical conditions and show that several genes, sRNAs, and operons exhibit conditional phenotypes not reported by previous high-throughput efforts. Second, we evaluate systematically targeting non-genic features (promoters and TFBSs) in theE. coligenome. We show that promoter-targeting guides can be used to add phenotypic confidence to promoter annotations and verify computationally predicted promoters. In contrast to prior studies, we find that promoter knockdowns exhibit a strong targeting orientation dependency where targeting the non-template strand of the promoter closest to the target gene is more effective in knocking down gene expression than other promoter targeting orientations. Unlike eukaryotic genomes, we note that interpreting the effects of TFBS targeting is particularly challenging due to the small size of such features and their proximity to and overlap with other genomic features. Together, this work reveals novel conditionally essential gene phenotypes, provides a characterized set of sgRNAs for futureE. coliCRISPRi screens, and highlights considerations for CRISPRi library design and screening for microbial genome characterization.
Type I toxin-antitoxin systems contribute to mobile genetic elements maintenance inClostridioides difficileand can be used as a counter-selectable marker for chromosomal manipulation
Authors: Peltier Johann , Hamiot Audrey , Garneau Julian R. , Boudry Pierre , Maikova Anna , Fortier Louis-Charles , Dupuy Bruno , Soutourina Olga 
Published: March 2020

ABSTRACTToxin-antitoxin (TA) systems are widespread on mobile genetic elements as well as in bacterial chromosomes. According to the nature of the antitoxin and its mode of action for toxin inhibition, TA systems are subdivided into different types. The first type I TA modules were recently identified in the human enteropathogenClostridioides(formerlyClostridium)difficile. In type I TA, synthesis of the toxin protein is prevented by the transcription of an antitoxin RNA during normal growth. Here, we report the characterization of five additional type I TA systems present within phiCD630-1 and phiCD630-2 prophage regions ofC. difficile630. Toxin genes encode 34 to 47 amino acid peptides and their ectopic expression inC. difficileinduces growth arrest. Growth is restored when the antitoxin RNAs, transcribed from the opposite strand, are co-expressed together with the toxin genes. In addition, we show that type I TA modules located within the phiCD630-1 prophage contribute to its stability and mediate phiCD630-1 heritability. Type I TA systems were found to be widespread in genomes ofC. difficilephages, further suggesting their functional importance. We have made use of a toxin gene from one of type I TA modules ofC. difficileas a counter-selectable marker to generate an efficient mutagenesis tool for this bacterium. This tool enabled us to delete all identified toxin genes within the phiCD630-1 prophage, thus allowing investigation of the role of TA in prophage maintenance. Furthermore, we were able to delete the large 49 kb phiCD630-2 prophage region using this improved procedure.
Repression by theArabidopsisTOPLESS corepressor requires association with the core Mediator complex
Authors: Leydon Alexander R. , Wang Wei , Gala Hardik P. , Gilmour Sabrina , Juarez-Solis Samuel , Zahler Mollye L. , Zemke Joseph E. , Zheng Ning , Nemhauser Jennifer L. 
Published: March 2020

AbstractThe plant corepressor TOPLESS (TPL) is recruited to a large number of loci that are selectively induced in response to developmental or environmental cues, yet the mechanisms by which it inhibits expression in the absence of these stimuli is poorly understood. Previously, we had used the N-terminus ofArabidopsis thalianaTPL to enable repression of a synthetic auxin response circuit inSaccharomyces cerevisiae(yeast). Here, we leveraged the yeast system to interrogate the relationship between TPL structure and function, specifically scanning for repression domains. We identified a potent repression domain in Helix 8 located within the CRA domain, which directly interacted with the Mediator middle domain subunits Med21 and Med10. Interactions between TPL and Mediator were required to fully repress transcription in both yeast and plants. In contrast, we found that multimer formation, a conserved feature of many corepressors, had minimal influence on the repression strength of TPL.
Risk of preeclampsia in patients with genetic predisposition to common medical conditions: a case-control study
Authors: Gray Kathryn J. , Kovacheva Vesela P. , Mirzakhani Hooman , Bjonnes Andrew C. , Almoguera Berta , Wilson Melissa L. , Ingles Sue Ann , Lockwood Charles J. , Hakonarson Hakon , McElrath Thomas F. , Murray Jeffrey C. , Norwitz Errol R. , Karumanchi S. Ananth , Bateman Brian T. , Keating Brendan J. , Saxena Richa 
Published: March 2020

ABSTRACTObjectiveTo assess whether women with a genetic predisposition to medical conditions known to increase preeclampsia risk have an increased risk of preeclampsia in pregnancy.DesignCase-control study.Setting and populationPreeclampsia cases (n=498) and controls (n=1864) of European ancestry from 5 US sites genotyped on a cardiovascular gene-centric array.MethodsSignificant single nucleotide polymorphisms (SNPs) from 21 traits in 7 disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal, thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous, scaled genetic instrument with preeclampsia. Odds of preeclampsia were compared across quartiles of the genetic instrument and evaluated for significance using a test for trend.Main Outcome Measurespreeclampsia.ResultsAn increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of preeclampsia (DBP: overall OR 1.11 (1.01-1.21), p=0.025; BMI: OR 1.10 (1.00-1.20), p=0.042), while risk alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89 (0.82-0.97), p=0.008), driven primarily by pleiotropic effects of variants in theFADSgene region. The effect of DBP genetic loci was even greater in early-onset (<34 weeks) preeclampsia cases (OR 1.30 (1.08-1.56), p=0.005). For all other traits, the genetic instrument was not robustly associated with preeclampsia risk.ConclusionsThese results suggest that the underlying genetic architecture of preeclampsia is shared with other disorders, specifically hypertension and obesity.TWEETABLE ABSTRACTGenetic predisposition to increased diastolic blood pressure and obesity increases the risk of preeclampsia.
Evolution of a plant gene cluster in Solanaceae and emergence of metabolic diversity
Authors: Fan Pengxiang , Wang Peipei , Lou Yann-Ru , Leong Bryan J. , Moore Bethany M. , Schenck Craig A. , Combs Rachel , Cao Pengfei , Brandizzi Federica , Shiu Shin-Han , Last Robert L. 
Published: March 2020

AbstractPlants produce phylogenetically and spatially restricted, as well as structurally diverse specialized metabolites via multistep metabolic pathways. Hallmarks of specialized metabolic evolution include enzymatic promiscuity, recruitment of primary metabolic enzymes and genomic clustering of pathway genes. Solanaceae plant glandular trichomes produce defensive acylsugars, with aliphatic sidechains that vary in length across the family. We describe a tomato gene cluster on chromosome 7 involved in medium chain acylsugar accumulation due to trichome specific acyl-CoA synthetase and enoyl-CoA hydratase genes. This cluster co-localizes with a tomato steroidal alkaloid gene cluster forming a ‘supercluster’, and is syntenic to a chromosome 12 region containing another acylsugar pathway gene. We reconstructed the evolutionary events leading to emergence of this gene cluster and found that its phylogenetic distribution correlates with medium chain acylsugar accumulation across the Solanaceae. This work reveals dynamics behind emergence of novel enzymes from primary metabolism, gene cluster evolution and cell-type specific metabolite diversity.