bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Controlled Trials of Remdesivir in Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Sarfraz Azza , Sarfraz Zouina , Sanchez-Gonzalez Marcos , Michel Jack , Michel George , Frontela Odalys , Posado Jorge , Cardona Jose , Angueira Eugonia 
Published: August 2020

AbstractBackgroundThe first cases of the coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. No antiviral treatment options are currently available with proven clinical efficacy. However, preliminary findings from phase III trials suggest that remdesivir is an effective and safe treatment option for COVID-19 patients with both moderate and severe disease.ObjectiveThe aim of the present meta-analysis was to investigate whether remdesivir was effective for treating COVID-19 including reduced in-hospital adverse events, oxygen support, and mortality rates.MethodsAccording to PRISMA reporting guidelines, a review was conducted from January 1 2020 until 25 August 2020 with MeSH terms including COVID-19, COVID, coronavirus, SARS-CoV-2, remdesivir, adenosine nucleoside triphosphate analog, Veklury using MEDLINE, Scopus, and CINAHL Plus. A modified Delphi process was utilized to include the studies and ensure that the objectives were addressed. Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel Haenszel (M-H) random-effects method in Review Manager 5.4.ResultsRandomized controlled trials pooled in 3013 participants with 46.3% (n=1,395) in the remdesivir group and 53.7% (n=1,618) in the placebo group. The placebo group had a higher risk of mortality as compared to the intervention group with significant odds ratio (OR=0.61) (95% confidence interval of 0.45 0.82; P=0.001). There was minimal heterogeneity among the studies (I2=0%).ConclusionsOur findings suggest that remdesivir extends clinical benefits by reducing mortality, adverse events and oxygen support in moderate to severely ill COVID-19 patients. Concerted efforts and further randomized placebo-controlled trials are warranted to examine the potency of antiviral drugs and immune-pathological host responses contributing to severity of COVID-19.
Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta-analysis
Authors: Campbell Cori , Wang Tingyan , McNaughton Anna , Barnes Eleanor , Matthews Philippa C 
Published: August 2020

AbstractBackgroundHepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is the largest cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is not certain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore we performed a systematic review and meta-analysis to seek evidence for significant associations.MethodsMEDLINE, Embase and Web of Science databases were searched from 1stJanuary 2000 to 24thJune 2020 for English studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection. We extracted data for meta-analysis and report pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present.ResultsWe identified 40 observational studies reporting on associations of diabetes mellitus, hypertension, dyslipiaemia and obesity with HCC risk. Meta-analysis was possible for only diabetes mellitus due to the limited number of studies. Diabetes mellitus was associated with > 25% increase in hazards of HCC (fixed effects Hazards Ratio [HR] 1.26, 95% CI 1.20–1.32, random effects HR 1.36, 95% CI 1.23–1.49). This association was attenuated towards the null in sensitivity analysis restricted to studies adjusted for metformin use.ConclusionsIn adults with chronic HBV infection, diabetes mellitus is a significant risk factor for HCC, but further investigation of how antidiabetic drug use and glycaemic control influence this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
Health Disparities and COVID-19: A Retrospective Study Examining Individual and Community Factors Causing Disproportionate COVID-19 Outcomes in Cook County, Illinois, March 16-May 31, 2020
Authors: Unruh Larissa H , Dharmapuri Sadhana , Yinglin Xia , Soyemi Kenneth 
Published: August 2020

AbstractBackgroundEarly data from the COVID-19 pandemic suggests that the disease has had a disproportionate impact on communities of color causing higher infection and mortality rates within those communities.MethodsThis study used demographic data from the 2018 US census estimates, mortality data from the Cook County Medical Examiner’s office, and testing results from the Illinois Department of Public Health to perform both bivariate and multivariate regression analyses to explore the role race plays in COVID-19 outcomes at the individual and community levels.ResultsPrincipal findings show that: 1) while Black Americans make up 22% of Cook County’s population, they account for 36% of the county’s COVID-19 related deaths; 2) the average age of death from COVID-19 is seven years younger for minorities compared to Non-Hispanic White (White) decedents; 3) minorities were more likely than Whites to have seven of the top 10 co-morbidities at death; 4) residents of predominantly minority areas were twice as likely to test positive for COVID-19 (p = 0.0001, IRR 1.94, 95% CI 1.50, 2.50) than residents of predominantly White areas; and 5) residents of predominantly minority areas were 1.43 times more likely to die of COVID-19 than those in predominantly White areas (p = 0.03).ConclusionsThere are notable differences in COVID-19 related outcomes between racial and ethnic groups at individual and community levels. We hope that this study will scientifically illustrate the health disparities experienced by communities of color and help to address the underlying systemic inequalities still prevalent within our country.
Racial/Ethnic and Economic Segregation and Survival in the United States
Authors: Mejía-Guevara I. , Cullen M.R. , Tuljapurkar S. , Periyakoil V.S. , Rehkopf D. 
Published: August 2020

AbstractLife expectancy differences across racial/ethnic and economic groups persist in the U.S., but little is known about the combined effects of racial and income segregation in explaining old age survival across neighborhoods. We operationalized neighborhoods using census tracts, with 65,655 of them nested within 3,015 counties, nested within 49 states. We linked census track life table data for ages 45-74 (n=196,965) from the National Vital Statistics System with 5-year population estimates (2011-2015) stratified by race/ethnicity and income from the American Community Survey. We measured racial/ethnic and income segregation using the Index of Concentration of the Extremes at the census tract level, and the indexes of dissimilarity and exposure at the county level. Using three-level random intercept models, we assessed the direct and contextual relationship between survival at ages 45-74 with racial/ethnic and income segregation. Regardless of racial/ethnic stratification, a high concentration of neighborhood poverty was associated with a lower probability of survival relative to affluent neighborhoods (−4.83%; 95% CI −4.86, −4.79), although the relationship was larger in neighborhoods with high concentration of Blacks (−5.61%; −5.67, −5.54). Black-white county-level unevenness also had the largest negative association in those neighborhoods (−0.26%; −0.32, −0.20). Furthermore, Black isolation was negatively associated with a lower survival probability (−0.21%; −0.29, −0.13), but Hispanic isolation was positively associated (0.23%; 0.16, 0.30). Opposite relationships resulted from Black-White (0.06; −0.01, 0.14) and Hispanic-White (−0.13; −0.21, −0.05) interactions. Finally, high exposure to neighborhood poverty/affluence was associated with lower/higher probability of neighborhood survival, but the associations were the strongest for Blacks.SignificanceRacial/ethnic and income residential segregation have been associated with negative health outcomes and increased risk of mortality in the U.S. We tested the association between residential segregation at different geographic levels with the survival probability at ages 45-74 across rural/urban neighborhoods. Results indicate that the racial/ethnic and income geographic composition of the population are important factors for explaining this relationship. That is, poverty concentration, minority-white unevenness, and exposure to poverty, had detrimental outcomes for all communities, irrespective of their racial/ethnic composition. However, while minority-isolation/-exposure to whites is detrimental/protective for Black communities, the opposite happened in Hispanic communities. Our research provides important insights in understanding the extent to which residential segregation explains survival disparities across neighborhoods based on their race/ethnicity composition.
Breast cancer endocrine therapy exhausts adipocyte progenitors promoting weight gain and glucose intolerance
Authors: Scalzo Rebecca L. , Foright Rebecca M. , Hull Sara E. , Knaub Leslie A. , Johnson-Murguia Stevi , Kinanee Fotobari , Kaplan Jeffrey , Freije Benjamin , Verzosa Gregory , Houck Julie A. , Johnson Ginger , Zhang Anni M.Y. , Johnson James D. , MacLean Paul S. , Reusch Jane E.B. , Wright-Hobart Sabrina , Wellberg Elizabeth A. 
Published: August 2020

AbstractBreast cancer survivors treated with anti-estrogen therapies report weight gain and have an elevated risk of type 2 diabetes. Here, we show that current tamoxifen use associated with larger breast adipocyte diameter only in women with a BMI >30 kg/m2. To understand the mechanisms behind these clinical findings, we investigated the impact of estrogen deprivation and tamoxifen in a relevant pre-clinical model of obesity. Specifically, mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression ofEsr1observed in single-cell RNA sequencing of mesenchymal stem cells from adipose tissue, endocrine therapies induced adipose accumulation and preadipocyte expansion, but resulted in adipocyte progenitor depletion only in the context of HFHS. Consequently, 7-week endocrine therapy supported adipocyte hypertrophy and was associated with hepatic steatosis, hyperinsulinemia, insulin resistance, and glucose intolerance, particularly in HFHS fed females. Metformin or pioglitazone, glucose lowering drugs used to treat diabetes, prevented the effects of tamoxifen but not estrogen deprivation on adipocyte size and insulin resistance in HFHS-fed mice. This translational study suggests that endocrine therapies act via ERα to directly disrupt adipocyte progenitors and support adipocyte hypertrophy, leading to ectopic lipid deposition that may promote hyperinsulinemia, insulin resistance and type 2 diabetes. Interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.
Relabeling metabolic pathway data with groups to improve prediction outcomes
Authors: Basher Abdur Rahman M. A. , Hallam Steven J. 
Published: August 2020

AbstractMetabolic pathway inference from genomic sequence information is an integral scientific problem with wide ranging applications in the life sciences. As sequencing throughput increases, scalable and performative methods for pathway prediction at different levels of genome complexity and completion become compulsory. In this paper, we present reMap (relabelingmetabolic pathway data with groups) a simple, and yet, generic framework, that performs relabeling examples to a different set of labels, characterized as groups. A pathway group is comprised of a subset of statistically correlated pathways that can be further distributed between multiple pathway groups. This has important implications for pathway prediction, where a learning algorithm can revisit a pathway multiple times across groups to improve sensitivity. The relabeling process in reMap is achieved through an alternating feedback process. In the first feed-forward phase, a minimal subset of pathway groups is picked to label each example. In the second feed-backward phase, reMap’s internal parameters are updated to increase the accuracy of mapping examples to pathway groups. The resulting pathway group dataset is then be used to train a multi-label learning algorithm. reMap’s effectiveness was evaluated on metabolic pathway prediction where resulting performance metrics equaled or exceeded other prediction methods on organismal genomes with improved predictive performance.
MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions
Authors: Backx Elyne , Wauters Elke , Baldan Jonathan , Van Bulck Mathias , Michiels Ellis , Heremans Yves , De Paep Diedert Luc , Kurokawa Mineo , Goyama Susumu , Bouwens Luc , Jacquemin Patrick , Houbracken Isabelle , Rooman Ilse 
Published: August 2020

ABSTRACTMaintenance of the pancreatic acinar cell phenotype suppresses tumor formation. Hence, repetitive acute or chronic pancreatitis, stress conditions in which the acinar cells dedifferentiate, predispose for cancer formation in the pancreas. Dedifferentiated acinar cells acquire a large panel of duct cell-specific markers. However, it remains unclear to what extent dedifferentiated acini differ from native duct cells and which genes are uniquely regulating acinar cell dedifferentiation. Moreover, most studies have been performed in mice since the availability of human cells is scarce.Here, we applied a non-genetic lineage tracing method of human pancreatic exocrine acinar and duct cells that allowed cell-type-specific gene expression profiling by RNA sequencing. Subsequent to this discovery analysis, one transcription factor that was unique for dedifferentiated acinar cells was functionally characterized.RNA sequencing analysis showed that human dedifferentiated acinar cells expressed genes in ‘Pathways of cancer’ with prominence ofMECOM (EVI-1), atranscription factor that was not expressed by duct cells. During mouse embryonic development, pre-acinar cells also transiently expressed MECOM and in the adult mouse pancreas, MECOM was re-expressed when mice were subjected to acute and chronic pancreatitis, conditions in which acinar cells dedifferentiate. In human cells and in mice, MECOM expression correlated with and was directly regulated by SOX9. Mouse acinar cells that, by genetic manipulation, lose the ability to upregulate MECOM showed impaired cell adhesion, more prominent acinar cell death and suppressed acinar cell dedifferentiation by limited ERK signaling.In conclusion, we transcriptionally profiled the two major human pancreatic exocrine cell types, acinar and duct cells, during experimental stress conditions. We provide insights that in dedifferentiated acinar cells, cancer pathways are upregulated in which MECOM is a critical regulator that suppresses acinar cell death by permitting cellular dedifferentiation.
Evolution of flowering time in a selfing annual plant: Roles of adaptation and genetic drift
Authors: Gay Laurène , Dhinaut Julien , Jullien Margaux , Vitalis Renaud , Navascués Miguel , Ranwez Vincent , Ronfort Joëlle 
Published: August 2020

AbstractResurrection studies are a useful tool to measure how phenotypic traits have changed in populations through time. If these traits modifications correlate with the environmental changes that occurred during the time period, it suggests that the phenotypic changes could be a response to selection. Selfing, through its reduction of effective size, could challenge the ability of a population to adapt to environmental changes. Here, we used a resurrection study to test for adaptation in a selfing population ofMedicago truncatula, by comparing the genetic composition and flowering times across 22 generations. We found evidence for evolution towards earlier flowering times by about two days and a peculiar genetic structure, typical of highly selfing populations, where some multilocus genotypes (MLGs) are persistent through time. We used the change in frequency of the MLGs through time as a multilocus fitness measure and built a selection gradient that suggests evolution towards earlier flowering times. Yet, a simulation model revealed that the observed change in flowering time could be explained by drift alone, provided the effective size of the population is small enough (<150). These analyses suffer from the difficulty to estimate the effective size in a highly selfing population, where effective recombination is severely reduced.
Females and hermaphrodites of the gynodioeciousGeranium maculatumrespond similarly to soil nutrient availability
Authors: Putney Katharine , Wolf Mavis , Mason Chase , Chang Shu-Mei 
Published: August 2020

AbstractSexual dimorphism in plant growth and/or reproductive responses to the surrounding environment has been documented in some plant species. In gynodioecious plants, it is especially important to understand whether females and hermaphrodites differ in their response to environmental stressors, as the fitness of females relative to hermaphrodites determines the extent to which these separate sexes are maintained in natural populations. Soil nutrient availability is of particular importance given the different nutrient requirements of male and female sexual functions in plants. Here, we evaluated and compared the growth of females and hermaphrodites ofGeranium maculatumin response to varying levels of nutrients. Using a greenhouse experiment, we manipulated the overall nutrient, nitrogen, and phosphorus levels in the soil and measured growth, allocation, and leaf quality responses in both females and hermaphrodites. We found that sexes responded similarly in their growth and allocation responses to nutrient availability, albeit evidence that female leaf chlorophyll content may have increased more than that of hermaphrodites across soil nitrogen levels. Our findings demonstrate that hermaphrodites differ from females in terms of their physiological response to varying nutrient levels, however these physiological differences did not translate into meaningful growth or reproduction differences.
5’XP sRNA-seq: Efficient Identification of Transcripts With and Without 5’ Phosphorylation Reveals Evolutionary Conserved Small RNA
Authors: Kugelberg Unn , Nätt Daniel , Skog Signe , Kutter Claudia , Öst Anita 
Published: August 2020

ABSTRACTSmall RNA (sRNA) sequencing has been critical for our understanding of many cellular processes, including gene regulation. Nonetheless, the varying biochemical properties of sRNA, such as 5’ nucleotide modifications, makes many sRNA subspecies incompatible with common protocols for sRNA sequencing. Here we describe 5XP-seq that outlines a novel strategy that solves this problem. By tagging 5’P sRNA during library preparation, 5XP-seq combines an open approach that includes all types of 5’-terminal modifications (5’X), with a selective approach for 5-phosphorylated sRNA (5’P). We show that 5XP-seq not only enriches phosphorylated miRNA and piRNA but successfully discriminates these sRNA from all other sRNA species. We further demonstrate the importance of this strategy by successful inter-species validation of sRNAs that would have otherwise failed, including human to insect translation of several tRNA (tRFs) and rRNA (rRFs) fragments. By combining 5’ insensitive library strategies with 5’ sensitive tagging, we have solved an intrinsic bias in modern sRNA sequencing that will help us reveal the true complexity and the evolutionary significance of the sRNA world.
Inheritance of Rootstock Effects in Avocado (Persea americanaMill.) cv. Hass
Authors: Reyes-Herrera Paula H. , Muñoz-Baena Laura , Velásquez-Zapata Valeria , Patiño Laura , Delgado-Paz Oscar A. , Díaz-Diez Cipriano A. , Navas-Arboleda Alejandro A. , Cortés Andrés J. 
Published: August 2020

ABSTRACTGrafting is typically utilized to merge adapted seedling rootstocks with highly productive clonal scions. This process implies the interaction of multiple genomes to produce a unique tree phenotype. Yet, the interconnection of both genotypes obscures individual contributions to phenotypic variation (i.e. rootstock-mediated heritability), hampering tree breeding. Therefore, our goal was to quantify the inheritance of seedling rootstock effects on scion traits using avocado (Persea americanaMill.) cv. Hass as model fruit tree. We characterized 240 rootstocks from 8 avocado cv. Hass orchards in three regions of the province of Antioquia, in the northwest Andes of Colombia, using 13 microsatellite markers (simple sequence repeats – SSRs). Parallel to this, we recorded 20 phenotypic traits (including morphological, eco-physiological, and fruit yield and quality traits) in the scions for three years (2015–2017). Relatedness among rootstocks was inferred through the genetic markers and inputted in a ‘genetic prediction’ model in order to calculate narrow-sense heritabilities (h2) on scion traits. We used three different randomization tests to highlight traits with consistently significant heritability estimates. This strategy allowed us to capture five traits with significant heritability values that ranged from 0.33 to 0.45 and model fits (R2) that oscillated between 0.58 and 0.74 across orchards. The results showed significance in the rootstock effects for four complex harvest and quality traits (i.e. total number of fruits, number of fruits with exportation quality, and number of fruits discarded because of low weight or thrips damage), while the only morphological trait that had a significant heritability value was overall trunk height (an emergent property of the rootstock-scion interaction). These findings suggest the inheritance of rootstock effects, beyond root phenotype, on a surprisingly wide spectrum of scion traits in ‘Hass’ avocado. They also reinforce the utility of SSR markers for relatedness reconstruction and genetic prediction of complex traits. This research is, up to date, the most cohesive evidence of narrow-sense inheritance of rootstock effects in a tropical fruit tree crop. Ultimately, our work reinforces the importance of considering the rootstock-scion interaction to broaden the genetic basis of fruit tree breeding programs, while enhancing our understanding of the consequences of grafting.