bluuebunny/crossref_metadata_2025_split huggingface dataset:
High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy inLeishmania donovani
Authors: Negreira Gabriel H , Monsieurs Pieter , Imamura Hideo , Maes Ilse , Kuk Nada , Yagoubat Akila , Van den Broeck Frederik , Sterkers Yvon , Dujardin Jean-Claude , Domagalska Malgorzata A 
Published: November 2021

AbstractLeishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two clonal populations of Leishmania promastigotes representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations, affecting a defined subset of chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.
Identification and classification of reverse transcriptases in bacterial genomes and metagenomes
Authors: Sharifi Fatemeh , Ye Yuzhen 
Published: November 2021

Abstract
Reverse transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) systems in prokaryotes. Different classes of RTs can play different roles, such as template switching and mobility in group II introns, spacer acquisition in CRISPR-Cas systems, mutagenic retrohoming in DGRs, programmed cell suicide in Abi systems, and recently discovered phage defense in retrons. While some classes of RTs have been studied extensively, others remain to be characterized. There is a lack of computational tools for identifying and characterizing various classes of RTs. In this study, we built a tool (called myRT) for identification and classification of prokaryotic RTs. In addition, our tool provides information about the genomic neighborhood of each RT, providing potential functional clues. We applied our tool to predict RTs in all complete and draft bacterial genomes, and created a collection that can be used for exploration of putative RTs and their associated protein domains. Application of myRT to metagenomes showed that gut metagenomes encode proportionally more RTs related to DGRs, outnumbering retron-related RTs, as compared to the collection of reference genomes. MyRT is both available as a standalone software (https://github.com/mgtools/myRT) and also through a website (https://omics.informatics.indiana.edu/myRT/).
Smoking Patterns Among Urban Alaska Native and American Indian Adults: The Alaska EARTH 10-Year Follow-up Study
Authors: Patten Christi A , Hiratsuka Vanessa Y , Nash Sarah H , Day Gretchen , Redwood Diana G , Beans Julie A , Howard Barbara V , Umans Jason G , Koller Kathryn R 
Published: November 2021

AbstractIntroductionData on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use.Aims and MethodsEARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up.ResultsCurrent smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking &lt;10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men.ConclusionsOur project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people.ImplicationsThis study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people.
Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial
Authors: Foulds Jonathan , Cobb Caroline O , Yen Miao-Shan , Veldheer Susan , Brosnan Phoebe , Yingst Jessica , Hrabovsky Shari , Lopez Alexa A , Allen Sophia I , Bullen Christopher , Wang Xi , Sciamanna Chris , Hammett Erin , Hummer Breianna L , Lester Courtney , Richie John P , Chowdhury Nadia , Graham Jacob T , Kang Le , Sun Shumei , Eissenberg Thomas 
Published: November 2021

Abstract

Introduction
The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute.

Methods
This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization.

Results
At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9–104.9] and 3.5 [95% CI = 1.2–10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130).

Conclusions
When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute.

Implications
The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.
Papering Over Protest: Contentious Politics and Archival Suppression in Early Modern Venice
Authors: van Gelder Maartje , de Vivo Filippo 
Published: November 2021

Abstract
This article studies the intertwined processes of popular protest and archival suppression in early modern Venice. It concentrates on a cycle of contention extending over several months in 1569, including a labour protest that started among the workers of the state shipyard and turned into a large revolt, anonymous placards and food riots. Such was the extent of the unrest that a major explosion in the shipyard raised suspicion of sabotage. Eventually, the government had to capitulate to the workers’ demands. This cycle of protests in Venice, a city normally renowned for peace and concord, has left minimal traces in the official records: the government tried to suppress the protests not only in practice but also on paper. It carried out convictions in secret, obliterated the revolt from its archives, buried any mention of protest under countless other records, and elided dissent from published histories. By using a variety of non-governmental sources, it is possible to investigate how contentious politics were written out of government records, and hence of history. Manipulating archives was always easier than subduing people: the more power was contested in the streets, the more it needed to be asserted in the archive.
The Effects of Benoxacor on the Liver and Gut Microbiome of C57BL/6 Mice
Authors: Simonsen Derek , Cady Nicole , Zhang Chunyun , Shrode Rachel L , McCormick Michael L , Spitz Douglas R , Chimenti Michael S , Wang Kai , Mangalam Ashutosh , Lehmler Hans-Joachim 
Published: November 2021

AbstractThe toxicity of many “inert” ingredients of pesticide formulations, such as safeners, is poorly characterized, despite evidence that humans may be exposed to these chemicals. Analysis of ToxCast data for dichloroacetamide safeners with the ToxPi tool identified benoxacor as the safener with the highest potential for toxicity, especially liver toxicity. Benoxacor was subsequently administered to mice via oral gavage for 3 days at concentrations of 0, 0.5, 5, and 50 mg/kg bodyweight (b.w.). Bodyweight-adjusted liver and testes weights were significantly increased in the 50 mg/kg b.w. group. There were no overt pathologies in either the liver or the intestine. 16S rRNA analysis of the cecal microbiome revealed no effects of benoxacor on α- or β-diversity; however, changes were observed in the abundance of certain bacteria. RNAseq analysis identified 163 hepatic genes affected by benoxacor exposure. Benoxacor exposure expressed a gene regulation profile similar to dichloroacetic acid and the fungicide sedaxane. Metabolomic analysis identified 9 serum and 15 liver metabolites that were affected by benoxacor exposure, changes that were not significant after correcting for multiple comparisons. The activity of antioxidant enzymes was not altered by benoxacor exposure. In vitro metabolism studies with liver microsomes and cytosol from male mice demonstrated that benoxacor is enantioselectively metabolized by cytochrome P450 enzymes, carboxylesterases, and glutathione S-transferases. These findings suggest that the minor toxic effects of benoxacor may be due to its rapid metabolism to toxic metabolites, such as dichloroacetic acid. This result challenges the assumption that inert ingredients of pesticide formulations are safe.
Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats
Authors: Mesnage Robin , Ibragim Mariam , Mandrioli Daniele , Falcioni Laura , Tibaldi Eva , Belpoggi Fiorella , Brandsma Inger , Bourne Emma , Savage Emanuel , Mein Charles A , Antoniou Michael N 
Published: November 2021

Abstract
Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate.
A Forward Genetic Screen in Sclerotinia sclerotiorum Revealed the Transcriptional Regulation of Its Sclerotial Melanization Pathway
Authors: Xu Yan , Ao Kevin , Tian Lei , Qiu Yilan , Huang Xingchuan , Liu Xueru , Hoy Ryan , Zhang Yishan , Rashid Khalid Youssef , Xia Shitou , Li Xin 
Published: November 2021

Most plant fungal pathogens that cause worldwide crop losses are understudied, due to various technical challenges. With the increasing availability of sequenced whole genomes of these non-model fungi, effective genetic analysis methods are highly desirable. Here, we describe a newly developed pipeline, which combines forward genetic screening with high-throughput next-generation sequencing to enable quick gene discovery. We applied this pipeline in the notorious soilborne phytopathogen Sclerotinia sclerotiorum and identified 32 mutants with various developmental and growth deficiencies. Detailed molecular studies of three melanization-deficient mutants provide a proof of concept for the effectiveness of our method. A master transcription factor was found to regulate melanization of sclerotia through the DHN (1,8-dihydroxynaphthalene) melanin biosynthesis pathway. In addition, these mutants revealed that sclerotial melanization is important for sclerotia survival under abiotic stresses, sclerotial surface structure, and sexual reproduction. Foreseeably, this pipeline can be applied to facilitate efficient in-depth studies of other non-model fungal species in the future. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Is gabapentin a safe and effective treatment for nonneuropathic pain?
Authors: Migeon Meghan 
Published: November 2021

ABSTRACT
A review of the recent literature found that compared with placebo or other pain medications, gabapentin did not significantly reduce nonneuropathic pain. The drug also is associated with an increased risk of adverse reactions, including somnolence, dizziness, and nausea. Given the lack of efficacy and risk of adverse reactions, gabapentin should not be used for nonneuropathic pain.
Metabolic acidosis in a lactating woman induced by a deliberate ketogenic diet
Authors: Hong Michelle J. , Schwartz Lauren E. , Ward Hillary H. , Morgan Jason C. , Jacoby Jeanne L. 
Published: November 2021

ABSTRACT
This article describes a rare case of lactation ketoacidosis in a patient who started a ketogenic diet while nursing an infant and toddler. The patient presented to the ED with a history of nausea, vomiting, and postural dizziness, and was found to have a significant metabolic acidosis and elevated lipase level. The metabolic changes induced in this patient could occur in anyone with high metabolic demands who also is on a strict ketogenic diet. The case highlights the importance of a dietary history in patients with unexplained metabolic derangements.
Decisional Regret Among Older Adults Undergoing Corrective Surgery for Adult Spinal Deformity: A Single Institutional Study
Authors: Adogwa Owoicho , Caruso James P. , Eldridge Cody M. , Singh Ravinderjit , Chilakapati Sai , Deme Palvasha , Stutzman Sonja , Aoun Salah G. , Naik Aanand D. , Bagley Carlos A. , Makris Una 
Published: November 2021

Study Design.
Retrospective.

Objective.
To investigate the prevalence of decisional regret among older adults undergoing surgery for adult spinal deformity (ASD).

Summary of Background Data.
Among older adults (≥65 years old), ASD is a leading cause of disability, with a population prevalence of 60% to 70%. While surgery is beneficial and results in functional improvement, in over 20% of older adults outcomes from surgery are less desirable.

Methods.
Older adults with ASD who underwent spinal surgery at a quaternary medical center from January 1, 2016 to March 1, 2019, were enrolled in this study. Patients were categorized into medium/high or low-decisional regret cohorts based on their responses to the Ottawa decision regret questionnaire. Decisional regret assessments were completed 24 months after surgery. The primary outcome measure was prevalence of decisional regret after surgery. Factors associated with high decisional regret were analyzed by multivariate logistic regression.

Results.
A total of 155 patients (mean age, 69.5 yrs) met the study inclusion criteria. Overall, 80% agreed that having surgery was the right decision for them, and 77% would make the same choice in future. A total of 21% regretted the choice that they made, and 21% responded that surgery caused them harm. Comparing patient cohorts reporting medium/high- versus low-decisional regret, there were no differences in baseline demographics, comorbidities, invasiveness of surgery, length of stay, discharge disposition, or extent of functional improvement 12-months after surgery. After adjusting for sex, American Society of Anesthesiologists score, invasiveness of surgery, and presence of a postoperative complication, older adults with preoperative depression had a 4.0 fold increased odds of high-decisional regret (P
= 0.04). Change in health related quality of life measures were similar between all groups at 12-months after surgery.

Conclusion.
While the majority of older adults were appropriately counseled and satisfied with their decision, one-in-five older adults regret their decision to undergo surgery. Preoperative depression was associated with medium/high decisional regret on multivariate analysis.

Level of Evidence: 4
Calculating Ex-ante Utilities From the Modified Japanese Orthopedic Association Score
Authors: Jiang Eric X. , Fisk Felicity E. , Taliaferro Kevin , Pahuta Markian A. 
Published: November 2021

Study Design.
General population utility valuation study.

Objective.
The aim of this study was to develop a technique for calculating utilities from the modified Japanese Orthopedic Association (mJOA) Score.

Summary of Background Data.
The ability to calculate quality-adjusted life-years (QALYs) for degenerative cervical myelopathy (DCM) would enhance treatment decision making and facilitate economic analysis. QALYs are calculated using utilities.

Methods.
We recruited a sample of 760 adults from a market research panel. Using an online discrete choice experiment, participants rated eight choice sets based on mJOA health states. A multiattribute utility function was estimated using a mixed multinomial-logit regression model. The sample was partitioned into a training set used for model fitting and validation set used for model evaluation.

Results.
The regression model demonstrated good predictive performance on the validation set with an area under the curve of 0.81 (95% confidence interval: 0.80–0.82)). The regression model was used to develop a utility scoring rubric for the mJOA. Regression results revealed that participants did not regard all mJOA domains as equally important. The rank order of importance was (in decreasing order): lower extremity motor function, upper extremity motor function, sphincter dysfunction, upper extremity sensation.

Conclusion.
This study provides a simple technique for converting the mJOA score to utilities and quantify the importance of mJOA domains. The ability to evaluate QALYs for DCM will facilitate economic analysis and patient counseling. Clinicians should heed these findings and offer treatments that maximize function in the attributes viewed most important by patients.

Level of Evidence: 3
COVID-19, the Pandemic of the Century and Its Impact on Cardiovascular Diseases
Authors: Zhang Yuanyuan , Wang Mingjie , Zhang Xian , Liu Tianxiao , Libby Peter , Shi Guo-Ping 
Published: November 2021

Abstract
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely ranks among the deadliest diseases in human history. As with other coronaviruses, SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. COVID-19 has upended lives worldwide. Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications, while patients have avoided hospital visits because of limited resources and the fear of infection, thereby increasing out-hospital mortality due to delayed diagnosis and treatment. Clinical observations show that sex, age, and race all influence the risk for SARS-CoV-2 infection, as do hypertension, obesity, and pre-existing cardiovascular conditions. Many hospitalized COVID-19 patients suffer cardiac injury, acute coronary syndromes, or cardiac arrhythmia. SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis, endothelial cell damage and dysfunction, oxidative stress and reactive oxygen species production, vasoconstriction, fibrotic and thrombotic protein expression, vascular permeability and microvascular dysfunction, heart inflammatory cell accumulation and activation, and a cytokine storm. Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors, angiotensin receptor blockers, steroids, aspirin, statins, and PCSK9 inhibitors. This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.