bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation Training Improves Trainee Technical Skill and Procedural Attitudes in Endoscopic Gastrostomy Tube Placement
Authors: Wright Andrew P. , Patel Anish H. , Farida Jeremy P. , Suresh Suraj , Rizk Rafat S. , Prabhu Anoop 
Published: May 2021

Introduction
Percutaneous endoscopic gastrostomy (PEG) tube placement remains a core competency of gastroenterology fellowship, although this procedure is performed infrequently. Some training programs lack sufficient procedural volume for trainees to develop confidence and competence in this procedure. We aimed to determine the impact of a simulation-based educational intervention on trainee technical skill and procedural attitudes in simulated PEG tube placement.

Methods
Gastroenterology fellows were invited to participate in the study. Baseline procedural attitudes toward PEG tube placement (self-confidence, perceived skill level, perceived level of required supervision) were assessed before simulation training using a Likert scale. Baseline technical skills were assessed by video recording–simulated PEG tube placement on a PEG tube simulator with scoring using a procedural checklist. Fellows next underwent individualized simulation training and repeated simulated PEG tube placement until greater than 90% of checklist items were achieved. Procedural attitudes were reassessed directly after the simulation. Technical skill and procedural attitudes were then reassessed 6 to 12 weeks later (delayed posttraining).

Results
Twelve fellows completed the study. Simulation training led to significant improvement in technical skill at delayed reassessment (52.9 ± 14.3% vs. 78.0 ± 8.9% correct, P = 0.0002). Simulation training also led to significant immediate improvements in self-confidence (2.1 ± 0.7 vs. 3.1 ± 0.3, P = 0.001), perceived skill level (2.2 ± 1.0 vs. 4 ± 1.1, P < 0.001), and perceived level of required supervision (2.2 ± 0.9 vs. 3.2 ± 0.6, P = 0.003).

Conclusions
Simulation training led to sustained improvements in gastroenterology fellows' technical skill and procedural attitudes in PEG tube placement. Incorporation of simulation curricula in gastroenterology fellowships for this infrequently performed procedure should be considered.
The Effect of Increasing Donor Age on Myocardial Ischemic Tolerance in a Rodent Model of Donation After Circulatory Death
Authors: Villanueva Jeanette E. , Chew Hong C. , Gao Ling , Doyle Aoife , Scheuer Sarah E. , Hicks Mark , Jabbour Andrew , Dhital Kumud K. , Macdonald Peter S. 
Published: May 2021

Background.
Hearts from older donors or procured via donation after circulatory death (DCD) can alleviate transplant waitlist; however, these hearts are particularly vulnerable to injury caused by warm ischemic times (WITs) inherent to DCD. This study investigates how the combination of increasing donor age and pharmacologic supplementation affects the ischemic tolerance and functional recovery of DCD hearts and how age impacts cardiac mitochondrial respiratory capacity and oxidative phosphorylation.

Methods.
Wistar rats (12-, 18-, and 24-mo-old) were subjected to DCD with 20-min fixed WIT. Hearts were procured, instrumented onto a Langendorff perfusion circuit, flushed with Celsior preservation solution with or without supplementation (glyceryl trinitrate [GTN]/erythropoietin [EPO]/zoniporide [Z]) and perfused (Krebs-Henseleit buffer, 37°C Langendorff 30-min, working 30-min). Cardiac functional recovery of aortic flow (AF), coronary flow (CF), cardiac output (CO), and lactate dehydrogenase release were measured. Native heart tissue (3-, 12-, and 24-mo) were assessed for mitochondrial respiratory capacity.

Results.
Unsupplemented 18- and 24-month DCD hearts showed a 6-fold decrease in AF recovery relative to unsupplemented 12-month DCD hearts. GTN/EPO/Z supplementation significantly increased AF and CO recovery of 18-month DCD hearts to levels comparable to supplemented 12-month hearts; however, GTN/EPO/Z did not improve 24-month DCD heart recovery. Compared to 12-month heart tissue, 24-month hearts exhibited significantly impaired mitochondrial oxygen flux at complex I, II, and uncoupled maximal respiration stage.

Conclusions.
Reduced ischemic tolerance after DCD was associated with increasing age. Pharmacologic supplementation improves functional recovery of rat DCD hearts but only up to age 18 months, possibly attributed to a decline in mitochondrial respiratory capacity with increasing age.
COVID-19 Serology in New York State Using a Multiplex Microsphere Immunoassay
Authors: Hunt Danielle T. , Yates Jennifer L. , Kulas Karen E. , Carson Kyle , Lamson Theresa , Demarest Valerie , Furuya Andrea , Howard Kelly , Marchewka Mary , Stone Randy , Tucker Heidi , Warszycki Casey , Yee Jim , Yang He S. , Racine-Brzostek Sabrina , Zhao Zhen , Ejemel Monir , Li Qi , Wang Yang , Fernando Sebastian , La Carpia Francesca , Hod Eldad A. , McDonough Kathleen A. , Lee William T. 
Published: May 2021

AbstractThe emergence of SARS-CoV-2, leading to COVID-19, necessitated the development of new molecular and serological tests. Here, we describe a multiplexed serological assay developed as the global pandemic moved into New York State in the spring of 2020. The original microsphere immunoassay used a target antigen from the SARS-CoV-1 virus responsible for the 2003 SARS outbreak, but evolved to incorporate multiple SARS-CoV-2 protein antigens (nucleocapsid, spike and spike domains, spike and nucleocapsid proteins from seasonal human coronaviruses). Besides being highly versatile due to multiplex capabilities, the assay was highly specific and sensitive and adaptable to measuring both total antibodies and antibody isotypes. While determining the assay performance characteristics, we were able to identify antibody production patterns (e.g., kinetics of isotypes, individual variations) for total antibodies and individual antibody classes. Overall, the results provide insights into the laboratory response to new serology needs, and how the evolution and fine-tuning of a serology assay helped contribute to a better understanding of the antibody response to SARS-CoV-2.
Early mineralocorticoid receptor antagonism in diabetic nephropathy limits albuminuria by preserving the glomerular endothelial glycocalyx
Authors: Crompton Michael , Ferguson Joanne K. , Ramnath Raina D. , Onions Karen L. , Ogier Anna S. , Down Colin J. , Skinner Laura , Dixon Lauren K. , Sutak Judit , Harper Steven J. , Pontrelli Paola , Gesualdo Loreto , Welsh Gavin I. , Foster Rebecca R. , Satchell Simon C. , Butler Matthew J. 
Published: May 2021

AbstractThe glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier (GFB). We have previously shown that excess mineralocorticoid receptor (MR) activation causes GEnGlx damage and albuminuria. Damage to the GEnGlx occurs early in the pathogenesis of diabetic nephropathy (DN). Here we sought to determine whether MR antagonism with spironolactone could prevent the development of albuminuria in diabetes, by preserving the GEnGlx to maintain the GFB. Streptozotocin-induced diabetic Wistar rats developed increased glomerular albumin permeability (Ps’alb) and albuminuria, with associated GEnGlx loss and increases in plasma and urine active matrix metalloproteinase 2 (MMP2). MR antagonism reduced urine active MMP2, preserved the GEnGlx, restored Ps’alb to control values and prevented diabetes-induced albuminuria progression. Enzymatic degradation of the GEnGlx, with hyaluronidase, reversed the effect of MR antagonism in diabetic rats, confirming the importance of GEnGlx preservation in this model. Using this model we validated a novel fluorescent profile peak-to-peak confocal imaging technique and applied it to assess GEnGlx damage on renal biopsies from patients with DN and compared them to healthy controls. We confirmed that GEnGlx loss occurs in human DN and may contribute to the disease phenotype. Taken together our work suggests GEnGlx preservation as an important novel mechanism for reno-protection by MR inhibitors in diabetes.Translational StatementMineralocorticoid receptor (MR) antagonists reduce albuminuria in diabetic nephropathy (DN), but side effects limit their clinical utility, and the mechanism is unknown. This paper demonstrates that MR antagonism prevented the development of glomerular endothelial glycocalyx (GEnGlx) dysfunction and albuminuria. Highly specific, enzyme mediated, removal of the GEnGlx abolished this effect, confirming the importance of EnGlx preservation in this model. Our data also confirm that GEnGlx damage occurs in human DN and may contribute to the clinical phenotype. This work suggests directly targeting glycocalyx preservation in DN could reproduce the protective effects seen with MR inhibition, whilst avoiding side effects.
Evolutionary assembly of cooperating cell types in an animal chemical defense system
Authors: Brückner Adrian , Badroos Jean M. , Learsch Robert W. , Yousefelahiyeh Mina , Kitchen Sheila A. , Parker Joseph 
Published: May 2021

SummaryA long-standing challenge in biology is explaining how the functions of multicellular organs emerge from the underlying evolution of cell types. We deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. We show that gland function was pieced together via assembly of two cell types that manufacture distinct compounds. One cell type forms a chemical reservoir in the beetle’s abdomen and produces alkane and ester compounds. We demonstrate that this cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, and executes its function via a mosaic of enzymes sourced from each parental cell type. The second cell type synthesizes noxious benzoquinones using a chimeric pathway derived from conserved cellular energy and cuticle formation pathways. We present evidence that evolution of each cell type was shaped by coevolution between the two cell types: the benzoquinones produced by the second cell type dissolve in solvents produced by the first, yielding a potent secretion that confers adaptive value onto the gland as a whole. Our findings illustrate how cooperation between cell types can arise, generating new, organ-level behaviors.
Effects of Slow Oscillatory Transcranial Alternating Current Stimulation on Motor Cortical Excitability Assessed by Transcranial Magnetic Stimulation
Authors: Geffen Asher , Bland Nicholas , Sale Martin V 
Published: May 2021

AbstractConverging evidence suggests that transcranial alternating current stimulation (tACS) may entrain endogenous neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation (although only for a few oscillatory cycles following the cessation of stimulation). However, observing entrainment in the electroencephalograph (EEG) during stimulation is extremely difficult due to the presence of complex tACS artefacts. The present study assessed entrainment to slow oscillatory (SO) tACS by measuring motor cortical excitability across different oscillatory phases during (i.e., online) and outlasting (i.e., offline) stimulation. 30 healthy participants received 60 trials of intermittent SO tACS (0.75 Hz; 16s on / off interleaved) at an intensity of 2mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation (TMS) of the hand region of the primary motor cortex (M1HAND) to induce motor evoked potentials (MEPs) in the contralateral thumb. MEPs were acquired at four time-points within each trial – early online, late online, early offline, and late offline – as well as at the start and end of the overall stimulation period (to probe longer-lasting aftereffects of tACS). A significant increase in MEP amplitude was observed from pre-to post-tACS (P = 0.013) and from the first to the last tACS block (P = 0.008). However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism.
A Trifector of New Insights into Ovine Footrot for Infection Drivers, Immune Response and Host Pathogen Interactions
Authors: Blanchard Adam M. , Staley Ceri E. , Shaw Laurence , Wattegedera Sean R , Baumbach Christina-Marie , Michler Jule K. , Rutland Catrin , Back Charlotte , Newbold Nerissa , Entrican Gary , Tötemeyer Sabine 
Published: May 2021

AbstractFootrot is a polymicrobial infectious disease in sheep causing severe lameness, leading to one of the industry’s biggest welfare problems. The complex aetiology of footrot makes in-situ or in-vitro investigations difficult. Computational methods offer a solution to understanding the bacteria involved, how they may interact with the host and ultimately providing a way to identify targets for future hypotheses driven investigative work. Here we present the first combined global analysis of the bacterial community transcripts together with the host immune response in healthy and diseased ovine feet during a natural polymicrobial infection state using metatranscriptomics. The intra tissue and surface bacterial populations and the most abundant bacterial transcriptome were analysed, demonstrating footrot affected skin has a reduced diversity and increased abundances of, not only the causative bacteria Dichelobacter nodosus, but other species such as Mycoplasma fermentans and Porphyromonas asaccharolytica. Host transcriptomics reveals a suppression of biological processes relating to skin barrier function, vascular functions, and immunosurveillance in unhealthy interdigital skin, supported by histological findings that type I collagen (associated with scar tissue formation) is significantly increased in footrot affected interdigital skin comparted to outwardly healthy skin. Finally, we provide some interesting indications of host and pathogen interactions associated with virulence genes and the host spliceosome which could lead to the identification of future therapeutic targets.Impact StatementLameness in sheep is a global welfare and economic concern and footrot is the leading cause of lameness, affecting up to 70% of flocks in the U.K. Current methods for control of this disease are labour intensive and account for approximately 65% of antibiotic use in sheep farming, whilst preventative vaccines suffer from poor efficacy due to antigen competition. Our limited understanding of cofounders, such as strain variation and polymicrobial nature of infection mean new efficacious, affordable and scalable control measures are not receiving much attention. Here we examine the surface and intracellular bacterial populations and propose potential interactions with the host. Identification of these key bacterial species involved in the initiation and progression of disease and the host immune mechanisms could help form the basis of new therapies.
Histone acetyltransferases and deacetylases are required for virulence, conidiation, DNA damage repair, and multiple stresses resistance of Alternaria alternata
Authors: Ma Haijie , Li Lei , Gai Yunpeng , Zhang Xiaoyan , Chen Yanan , Zhuo Xiaokang , Cao Yingzi , Jiao Chen , Gmitter Fred G. , Li Hongye 
Published: May 2021

SummaryHistone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5, RTT109, Elp3, Sas3, Sas2, Nat3) and 6 histone deacetylases (HDACs) (Hos2, Rpd3, Hda1, Hos3, Hst2, Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants (ΔGcn5, ΔRTT109, ΔElp3, ΔSas3, ΔNat3, ΔHos2, and ΔRpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3, Gcn5, Elp3, RTT109, Hos2), osmotic stress (Sas3, Gcn5, RTT109, Hos2), cell wall-targeting agents (Sas3, Gcn5, Hos2), and fungicide (Gcn5, Hos2). ΔGcn5, ΔSas3 and ΔHos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in ΔGcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover, ΔRTT109, ΔGcn5 and ΔHos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in ΔGcn5 and ΔHos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata.ImportanceIn filamentous fungi, HATs and HDACs have been found to be involved in growth, development, virulence, synthesis of secondary metabolites and multi-stress resistance. However, the role of all HATs and HDACs in the same fungal pathogen has not been systematically explored. Our study revealed that HATs and HDACs are required for the vegetative growth, conidiation, pathogenicity, multiple stresses resistance, DNA damage repair, and carbon source utilization in A. alternata. Moreover, HATs and HDACs identified in A. alternata are highly conserved in many notorious pathogenic fungi, such as Magnaporthe grisea and Candida albicans. Therefore, this study not only systematically reveals the biological functions of twelve histone acetylation-required enzymes for the first time, but also provides a foundation for future investigations in A. alternata or other pathogenic fungi.
Hypervirulent extensively-drug resistant (XDR) Klebsiella pneumoniae associated with complicated urinary tract infection in Northern India
Authors: Kaza Parinitha , Britto Xavier Basil , Mahindroo Jaspreet , Baker Stephen , Nguyen To Nguyen Thi , Mavuduru Ravimohan Suryanarayana , Mohan Balvinder , Taneja Neelam 
Published: May 2021

AbstractKlebsiella pneumoniae associated with hospital acquired infections in South Asia are frequently extensively-drug resistant (XDR), making treatment and control problematic. It is important to understand the epidemiology and genetic structure of XDR K. pneumoniae and to determine their potential to be hypervirulent (hv) through the presence of siderophores. Here, we characterized the genomes of 20 colistin-resistant XDR K. pneumoniae isolated from 16 patients with complicated UTI over a six-month period in a healthcare facility in northern India. The 16 organisms comprised five STs: ST14 (10/20), ST147 (5/20), ST231 (3/20), ST2096 (1/20), and ST25 (1/20). Notably, several patients admitted to a single ward were infected with the same ST, potentially indicating a common infection source. Additionally, some patients had recurrent infections with multiple STs that were circulating concurrently in a particular ward, providing further evidence for hospital transmission. Beta lactamase genes (blaCTX-M-1, blaSHV, blaLEN, and blaAMP-H) were present in all isolates and the blaNDM,blaOXA1-90, and blaOXA48 carbapenemases were present in 17, 18, and 3 isolates, respectively. Disruption of mgrB with various IS elements was identified in six organisms and was the most common mechanism of colistin resistance. The most frequent K type was K2 (11/20), followed by K10, K51, and K64. Notably, we identified one XDR convergent hypervirulent K. pneumoniae (hvKp) associated with prolonged hospitalisation (iuc+ybt+ESBL+OXA-1, OXA-48), belonging to ST2096. Our data suggest that convergent XDR-hvKp is circulating in our healthcare facility. We speculate that such organisms may have outbreak potential, warranting more effective antimicrobial stewardship and better infection control strategies.
Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy
Authors: Theiler Regan N. , Wick Myra , Mehta Ramila , Weaver Amy , Virk Abinash , Swift Melanie 
Published: May 2021

ABSTRACTBackgroundSARS-CoV-2 infection during pregnancy is associated with significant maternal morbidity and increased rates of preterm birth. For this reason, COVID-19 vaccine administration in pregnancy has been endorsed by multiple professional societies including ACOG and SMFM despite exclusion of pregnant women from initial clinical trials of vaccine safety and efficacy. However, to date little data exists regarding outcomes after COVID-19 vaccination of pregnant patients.Study DesignA comprehensive vaccine registry was combined with a delivery database for an integrated healthcare system to create a delivery cohort including vaccinated patients. Maternal sociodemographic data were examined univariately for factors associated with COVID-19 vaccination. Pregnancy and birth outcomes were analyzed, including a composite measure of maternal and neonatal pregnancy complications, the Adverse Outcome Index.ResultsOf 2002 patients in the delivery cohort, 140 (7.0%) received a COVID-19 vaccination during pregnancy and 212 (10.6%) experienced a COVID-19 infection during pregnancy. The median gestational age at first vaccination was 32 weeks (range 13 6/7-40 4/7), and patients vaccinated during pregnancy were less likely than unvaccinated patients to experience COVID-19 infection prior to delivery (1.4% (2/140) vs. 11.3% (210/1862)) P<0.001No maternal COVID-19 infections occurred after vaccination during pregnancy.Factors significantly associated with increased likelihood of vaccination included older age, higher level of maternal education, lower pre-pregnancy BMI, and use of infertility treatment for the current pregnancy. Tobacco or other substance use, Hispanic ethnicity, and higher gravidity were associated with a lower likelihood of vaccination. No significant difference in the composite adverse outcome (5.0% (7/140) vs. 4.9% (91/1862) P=0.95) or other maternal or neonatal complications, including thromboembolic events and preterm birth, was observed in vaccinated mothers compared to unvaccinated patients.ConclusionsVaccinated pregnant women in this birth cohort were less likely to experience COVID-19 infection compared to unvaccinated pregnant patients, and COVID-19 vaccination during pregnancy was not associated with increased pregnancy or delivery complications. Significant sociodemographic disparities in vaccine uptake and/or access were observed among pregnant patients, and future efforts should focus on outreach to low-uptake populations.