bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha globin gene copy number and hypertension risk among Black Americans
Authors: Ruhl A. Parker , Jeffries Neal , Yang Yu , Gutierrez Orlando M. , Muntner Paul , Naik Rakhi P. , Pecker Lydia H. , Mott Bryan T. , Zakai Neil A. , Safford Monika M. , Lange Leslie A. , Winkler Cheryl A. , Irvin Marguerite R. , Cushman Mary , Ackerman Hans C. 
Published: February 2022

ABSTRACTBACKGROUNDAlpha globin is expressed in the endothelial cells of human resistance arteries where it binds to endothelial nitric oxide synthase and limits release of the vasodilator nitric oxide. Genomic deletion of the alpha globin gene (HBA) is common among Black Americans and could lead to increased endothelial nitric oxide signaling and reduced risk of hypertension.METHODSCommunity-dwelling US adults aged 45 years or older were enrolled and examined from 2003 to 2007, followed by telephone every 6 months, and reexamined from 2013 to 2016. At both visits, trained personnel performed standardized, in-home blood pressure measurements and pill bottle review. Prevalent hypertension was defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg or anti-hypertensive medication use. Droplet digital PCR was used to determine HBA copy number. The associations of HBA copy number with prevalent hypertension, resistant hypertension, and incident hypertension were estimated using multivariable regression.RESULTSAmong 9,684 Black participants, 7,439 (77%) had hypertension at baseline and 1,044 of those had treatment-resistant hypertension. 1,000 participants were not hypertensive at baseline and participated in a follow up visit; 517 (52%) developed hypertension over median 9.2 years follow-up. Increased HBA copy number was not associated with prevalent hypertension (PR=1.00; 95%CI 0.98,1.02), resistant hypertension (PR=0.95; 95%CI 0.86,1.05), or incident hypertension (RR=0.96; 95%CI 0.86,1.07).CONCLUSIONSThere were no associations between increased HBA copy number and risk of hypertension. These findings suggest that variation in alpha globin gene copy number does not modify the risk of hypertension among Black American adults.
Severe hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants in France, December 2021 – January 2022: a retrospective, population-based, matched cohort study
Authors: Auvigne Vincent , Vaux Sophie , Le Strat Yann , Schaeffer Justine , Fournier Lucie , Tamandjou Cynthia , Montagnat Charline , Coignard Bruno , Levy-Bruhl Daniel , du Châtelet Isabelle Parent 
Published: February 2022

AbstractBackgroundA rapid increase in incidence of the SARS-CoV-2 Omicron variant occurred in France in December 2021, while the Delta variant was prevailing since July 2021. We aimed to determine whether the risk of a severe hospital event following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta.MethodsWe conducted a retrospective cohort study to compare severe hospital events (admission to intensive care unit or death) between Omicron and Delta symptomatic cases matched according to week of virological diagnosis and age. The analysis was adjusted for age, sex, vaccination status, presence of comorbidities and region of residence, using Cox proportional hazards model.FindingsBetween 06/12/2021-28/01/2022, 184 364 cases were included, of which 931 had a severe hospital event (822 Delta, 109 Omicron). The risk of severe event was lower among Omicron versus Delta cases; the difference in severity between the two variants decreased with age (aHR=0·11 95%CI: 0·07-0·17 among 40-64 years, aHR=0·51 95%CI: 0·26-1·01 among 80+ years). The risk of severe event increased with the presence of comorbidities (for very-high-risk comorbidity, aHR=4·18 95%CI: 2·88-6·06 among 40-64 years) and in males (aHR=2·29 95%CI: 1·83-2·86 among 40-64 years) and was higher in unvaccinated compared to primo-vaccinated (aHR=6·90 95%CI: 5·26-9·05 among 40-64 years). A booster dose reduced the risk of severe hospital event in 80+ years infected with Omicron (aHR=0·27; 95%CI: 0·11-0·65).InterpretationThis study confirms the lower severity of Omicron compared to Delta. However, the difference in disease severity is less marked in the elderly.
MatchMiner: An open source platform for cancer precision medicine
Authors: Klein Harry , Mazor Tali , Siegel Ethan , Trukhanov Pavel , Ovalle Andrea , Vecchio Fitz Catherine Del , Zwiesler Zachary , Kumari Priti , Van Der Veen Bernd , Marriott Eric , Yu Joyce , Albayrak Adem , Barry Susan , Keller Rachel B. , MacConaill Laura E. , Lindeman Neal , Johnson Bruce E. , Rollins Barrett J. , Do Khanh T. , Beardslee Brian , Shapiro Geoffrey , Hector-Barry Suzanne , Methot John , Sholl Lynette , Lindsay James , Hassett Michael J. , Cerami Ethan 
Published: February 2022

AbstractThe systematic deployment of next generation sequencing means patient tumors can be genomically profiled and specific genetic alterations can be targeted with precision medicine (PM) drugs. More therapeutic clinical trials are needed to test new PM drugs to advance precision medicine, however, the availability of comprehensive patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to PM trials. To facilitate enrollment onto PM trials, we developed MatchMiner. MatchMiner is an open-source platform to computationally match genomically profiled cancer patients to PM trials. Here, we describe MatchMiner’s capabilities, outline its deployment at Dana-Farber Cancer Institute (DFCI), and characterize its impact on PM trial enrollment. MatchMiner’s two primary goals are to (1) facilitate PM trial options for all patients, and (2) accelerate trial enrollment onto PM trials. MatchMiner has 3 main modes of use: (1) patient-centric, where a clinician looks up trial options for an individual patient, (2) trial-centric, where a trial team identifies candidate patients for their trial by setting up a filter, and (3) trial search, where a clinician can find trial options for patients that have external genomic reports. From the time MatchMiner was first deployed at DFCI in March 2016 through March 2021, we curated 354 PM trials containing a broad range of genomic and clinical eligibility criteria and MatchMiner facilitated 166 trial consents (MatchMiner consents, MMC) for 159 patients. To quantify MatchMiner’s impact on trial consent, we retrospectively measured time from genomic sequencing report date to trial consent date for the 166 MMC compared to trial consents not facilitated by MatchMiner (non-MMC). We found MMC consented to trials 55 days (22%) earlier than non-MMC. MatchMiner has enabled our clinicians to match patients to PM trials and accelerated the trial enrollment decision making process.
Reduction in postoperative opioid requirement associated with use of the NSS-2® Bridge device, a disposable auriculo-nerve field stimulator, and factors affecting the response in cancer patients undergoing abdominal surgical procedures
Authors: Chelly Jacques E. , Holtzman Matthew P. , Bartlett David L. , Choudry Haroon A. , Pingpank James F. , Zureikat Amer H. , Norton Brittany E. , Sadhasivam Senthilkumar K. , Vogt Keith M. 
Published: February 2022

ABSTRACTObjectiveDetermine the effect on opioid use after surgery with use of the NSS-2® Bridge device (NBD®) as a field nerve stimulator of the nerves innervating the ear for 5 days.MethodsThis was a prospective, randomized, double-blind, placebo-controlled trial investigating the effectiveness of the NBD® in reducing opioid (expressed as oral morphine equivalent; OME, mg) requirement in subjects undergoing abdominal surgery for cancer. A total of 53 subjects randomly assigned to either an active NBD® group or placebo group were included in the analysis. Secondary endpoints included pain using a verbal analogue scale (VAS, 0 = no pain to 10 = worst possible pain), time to ambulation, oral intake, first bowel movement, discharge from the hospital, and tolerability of the NBD®. Lastly, functional recovery rated using the 12-item Short Form Survey (SF12) assessed at three months.ResultsUse of the NBD® resulted in a 26% overall reduction in OME with no difference in pain level expressed as the area under the curve between postoperative day 1 to 5. respectively). This overall reduction accounts for a 6% reduction in OME in the patients undergoing laparoscopic surgery and a 39% reduction in OME and 25% reduction in pain in patients undergoing open surgery. The tolerability of the device was reported as excellent.ConclusionsCancer patients have been identified as a population at risk of developing opioid use disorders. This prospective, randomized, double-blind, placebo-controlled study, demonstrated that NBD® may be an effective alternative to the use of opioid postoperatively in patients undergoing abdominal surgery for cancer, especially in especially in patients undergoing open surgery and in elderly.
Developing and validating a multivariable prediction model for predicting costs of colon surgery
Authors: Taha Anas , Taha-Mehlitz Stephanie , Ochs Vincent , Enodien Bassey , Honaker Michael Drew , Frey Daniel M. , Cattin Philippe C. 
Published: February 2022

AbstractHospitals are burdened with predicting, calculating and managing various cost-affecting parameters regarding patients and their treatments. Accuracy in cost prediction is further affected if a patient suffers from other health issues which hinder the traditional prognosis. This can lead to an unavoidable deficit in the final revenue of medical centers. This study aims to determine whether machine learning (ML) algorithms can predict cost factors based on patients undergoing colon surgery. For the forecasting, multiple predictors will be taken into the model to provide a tool that can be helpful for hospitals to manage their costs which ultimately will lead to operating more cost-efficiently.. This proof of principle will lay the groundwork for an efficient ML-based prediction tool based on multicenter data from a range of international centers in the subsequent phases of the study. With a % MAPE result of 18 – 25.6, our model’s prediction showed decent results to forecast the costs regarding various diagnosed factors and surgical approaches. There is an urgent need for further studies on predicting cost factors, especially for cases with anastomotic leakage, to minimize unnecessary costs for hospitals.
Macrophages and glia are the dominant P2X7-expressing cell types in the gut nervous system – no evidence for a role of neuronal P2X7 receptors in colitis
Authors: Jooss Tina , Zhang Jiong , Rezzonico-Jost Tanja , Rissiek Björn , Koch-Nolte Friedrich , Magnus Tim , Zierler Susanna , Schemann Michael , Grassi Fabio , Nicke Annette 
Published: February 2022

SummaryBlockade or deletion of the pro-inflammatory P2X7 receptor channel has been shown to reduce tissue damage and symptoms in models of inflammatory bowel disease (IBD) and P2X7 receptors on enteric neurons were suggested to mediate neuronal death and associated motility changes. Here we used P2X7-specific antibodies and nanobodies as well as a BAC transgenic P2X7-EGFP reporter mouse model and P2rx7−/− controls to perform a detailed analysis of cell type-specific P2X7 expression and possible overexpression effects in the enteric nervous system. In contrast to previous studies, we did not detect P2X7 in neurons but found dominant expression in glia and macrophages which closely interact with the neurons. P2X7 overexpression per se did not induce significant pathological effects. Our data indicate that macrophages and/or glia account for P2X7-mediated neuronal damage in IBD and provide a refined basis for the exploration of P2X7-based therapeutic strategies.
Bergerac Strains of C. elegans Revisited: Expansion of Tc1 elements Impose a Significant Genomic and Fitness Cost
Authors: Daigle Austin T. , Deiss Thaddeus C. , Melde Robert H. , Bergthorsson Ulfar , Katju Vaishali 
Published: February 2022

ABSTRACTThe DNA transposon Tc1 was the first transposable element (TE) to be characterized in Caenorhabditis elegans and to date, remains the best-studied TE in Caenorhabditis worms. While Tc1 copy-number is regulated at approximately 30 copies in the laboratory N2/Bristol and the vast majority of C. elegans strains, the Bergerac strain and its derivatives have experienced a marked Tc1 proliferation. Given the historical importance of the Bergerac strain in the development of the C. elegans model, we implemented a modern genomic analysis of three Bergerac strains (CB4851, RW6999, and RW7000) in conjunction with multiple phenotypic assays to better elucidate the (i) genomic distribution of Tc1, and (ii) phenotypic consequences of TE deregulation for the host organism. The median estimates of Tc1 copy-number in the Bergerac strains ranged from 451 to 748, which is both (i) greater than previously estimated, and (ii) likely to be an underestimate of the actual copy-numbers since coverage-based estimates and ddPCR results both suggest higher Tc1 numbers. All three Bergerac strains had significantly reduced trait means compared to the N2 control for each of four fitness-related traits, with specific traits displaying significant differences between Bergerac strains. Tc1 proliferation was genome-wide, specific to Tc1, and particularly high on chromosomes V and X. There were fewer Tc1 insertions in highly expressed chromatin environments than expected by chance. Furthermore, Tc1 integration motifs were also less frequent in exon than non-coding sequences. The source of the proliferation of Tc1 in the Bergerac strains is specific to Tc1 and independent of other TEs. The Bergerac strains contain none of the alleles that have previously been found to derepress TE activity in C. elegans. However, the Bergerac strains had several Tc1 insertions near or within highly germline-transcribed genes which could account for the recent germline proliferation.
An integrative approach: using transcriptomic data and network analysis of transcriptional reprogramming in tomato response to PSTVd variants
Authors: Aviña-Padilla Katia , Zambada-Moreno Octavio , Herrera-Oropeza Gabriel Emilio , Jimenez-Limas Marco A. , Abrahamian Peter , Hammond Rosemarie W. , Hernández-Rosales Maribel 
Published: February 2022

AbstractViroids are minimal pathogens of angiosperms, consisting of non-coding RNAs that cause severe diseases in agronomic crops. Symptoms associated with viroid infection are linked to developmental alterations due to genetic regulation. To understand the global molecular mechanisms of host response, we implemented an omics approach to identify master transcription regulators (MTRs) and their differentially expressed targets in tomato infected with mild and severe variants of PSTVd. Our approach integrates root and leaf transcriptomic data, gene regulatory network analysis, and identification of affected biological processes. Overall, our results reveal that specific bHLH, MYB, and ERF transcription factors regulate genes involved in molecular mechanisms underlying critical signaling pathways. Functional enrichment of regulons shows that bHLH-MTRs are linked to metabolism and plant defense, while MYB-MTRs are involved in signaling regulation and hormone-related processes. Strikingly, a member of the bHLH-TF family have a potential specific role as a microprotein involved in the post-translational regulation of hormone signaling events. For the severe variant, ERF-MTRs are characteristic, while ZNF-TF, tf3a-TF, BZIP-TFs, and NAC-TF act as unique MTRs. Altogether, our results lay a foundation for further research on the PSTVd and host genome interaction, providing evidence for identifying potential key genes that influence symptom development in tomato plants.
Deepwater Horizoncrude oil reduces aerobic capacity of birds
Authors: Goodchild Christopher G. , Krall Jeffrey B. , Santhanakrishnan Arvind , DuRant Sarah E. 
Published: February 2022

ABSTRACTCrude oil spills can have catastrophic effects on marine and inland ecosystems, yet it is difficult to accurately quantify the extent of ecological damage caused by oil spills. For instance, avian population damage assessments conducted after large oil spills (e.g.,Deepwater Horizonspill) often focus on the number of visibly oiled birds. However, birds without visible oiling can exhibit hematological damage from oil ingestion. If such hematological responses limit oxygen deliver to tissues and impair aerobic performance, then energy-mediated effects from oil ingestion may ultimately affect endpoints of demographic significance (e.g., survival and reproduction). We investigated whether oil ingestion affects aerobic performance in birds by orally dosing zebra finches (Taeniopygia guttata) with 2 or 6 mL/kg of weathered MC252 crude oil for 28 days. After 14 and 28 days of dosing, we measured hematological indices (oxidative damage, packed cell volume [PCV], hemoglobin, reticulocytes), maximum metabolic rate (MMR), resting metabolic rate (RMR), and short-distance flight performance. Finches exposed to oil exhibited lower hemoglobin and PCV, higher reticulocyte counts, and greater oxidative damage. Shifts in these hematological indices appeared to alter organismal energetics, resulting in reduced MMR, RMR, and aerobic scope. Short-distance burst-flight was not negatively impacted by oil ingestion. Collectively, these results suggest oil ingestion impairs metabolic performance, which may negatively impact a bird’s ability to perform sustained energetically expensive activities (e.g., migration).SignificanceThe 2010Deepwater Horizonoil spill released an unprecedented volume of crude oil (MC252) into the northern Gulf of Mexico and contaminated 2100 km of shoreline habitat that serves as critical breeding grounds and migratory stop-over sites for birds. Here we describe the impact of oil ingestion on the aerobic capacity of zebra finches, a model songbird. Oil ingestion reduced maximum metabolic rate and aerobic scope, which may be caused in part by hematological damage. These data suggest oil ingestion limits the ability of birds to perform essential energetically demanding activities (e.g., migration, nest incubation), thus quantification of avian injury based on external oiling alone may underestimate the true impact of oil spills on avian populations.
IDSL.UFA assigns high confidence molecular formula annotations for untargeted LC/HRMS datasets in metabolomics and exposomics
Authors: Baygi Sadjad Fakouri , Banerjee Sanjay K , Chakraborty Praloy , Kumar Yashwant , Barupal Dinesh Kumar 
Published: February 2022

AbstractUntargeted LC/HRMS assays in metabolomics and exposomics aim to characterize the small molecule chemical space in a biospecimen. To gain maximum biological insights from these datasets, LC/HRMS peaks should be annotated with chemical and functional information including molecular formula, structure, chemical class and metabolic pathways. Among these, molecular formulas may be assigned to LC/HRMS peaks through matching theoretical and observed isotopic profiles (MS1) of the underlying ionized compound. For this, we have developed the Integrated Data Science Laboratory for Metabolomics and Exposomics – United Formula Annotation (IDSL.UFA) R package. In the untargeted metabolomics validation tests, IDSL.UFA assigned 54.31%-85.51% molecular formula for true positive annotations as the top hit, and 90.58%-100% within the top five hits. Molecular formula annotations were also supported by MS/MS data. We have implemented new strategies to 1) generate formula sources and their theoretical isotopic profiles 2) optimize the formula hits ranking for the individual and the aligned peak lists and 3) scale IDSL.UFA-based workflows for studies with larger sample sizes. Annotating the raw data for a publicly available pregnancy metabolome study using IDSL.UFA highlighted hundreds of new pregnancy related compounds, and also suggested presence of chlorinated perfluorotriether alcohols (Cl-PFTrEAs) in human specimens. IDSL.UFA is useful for human metabolomics and exposomics studies where we need to minimize the loss of biological insights in untargeted LC/HRMS datasets. The IDSL.UFA package is available in the R CRAN repository https://cran.r-project.org/package=IDSL.UFA. Detailed documentation and tutorials are also provided at www.ufa.idsl.me.
Heroin Self-Administration Induces Altered Dopamine Terminal Dynamics in the Nucleus Accumbens
Authors: George Brianna E. , Dawes Monica H. , Peck Emily G. , Jones Sara R. 
Published: February 2022

AbstractAdministration of heroin results in the engagement of multiple brain regions and the rewarding and addictive effects are mediated, at least partially, through activation of the mesolimbic dopamine system. However, less is known about dopamine system function following chronic exposure to heroin. Withdrawal from chronic heroin exposure is likely to drive a state of low dopamine in the nucleus accumbens (NAc), as previously observed during withdrawal from other drug classes. Thus, we aimed to investigate alterations in NAc dopamine terminal function following chronic heroin self-administration to identify a mechanism for dopaminergic adaptations. Adult male Long Evans rats were trained to self-administer heroin (0.05 mg/kg/inf, IV) and then placed on a long access (FR1, 6-hrs, unlimited inf, 0.05 mg/kg/inf) protocol to induce escalation of intake. After one day of withdrawal, male rats exhibited lower basal extracellular levels of dopamine as well as reduced dopaminergic responses to a heroin challenge (0.1 mg/kg/inf, IV). Following heroin self-administration, rats had decreased basal extracellular levels of dopamine and blunted dopamine response following a heroin challenge (0.1 mg/kg/inf, IV) in the NAc compared to saline controls. FSCV revealed that heroin-exposed rats have reduced stimulated dopamine release during tonic-like, single-pulse stimulations but increased phasic-like dopamine release during multi-pulse stimulation trains (5 pulses, 5-100Hz) in addition to an altered dynamic range of release stimulation intensities when compared to controls. Further, we found that presynaptic D3 autoreceptor and kappa-opioid receptor activity was increased following heroin self-administration. These results reveal a marked low dopamine state following heroin-exposure and suggest the combination of altered dopamine release dynamics may contribute to increased heroin seeking.