bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers
Authors: Jo Jinhee , Hu Chenlin , Begum Khurshida , Wang Weiqun , Le Thanh M , Agyapong Samantha , Hanson Blake M , Ayele Hossaena , Lancaster Chris , Jahangir Alam M , Gonzales-Luna Anne J , Garey Kevin W 
Published: December 2023

Abstract

Background
Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

Methods
This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18–40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations were assessed, and microbiome changes were compared.

Results
Sixteen healthy volunteers with a mean age of 26 (standard deviation [SD], 5) years were enrolled; 62.5% were male, and participants’ mean body mass index was 23.5 (SD, 4.0) kg/m2. Omadacycline was well tolerated with no safety signal differences between the 2 antibiotics. A rapid initial increase in fecal concentrations of omadacycline was observed compared to vancomycin, with maximum concentrations achieved within 48 hours. A significant difference in alpha diversity was observed following therapy in both the omadacycline and vancomycin groups (P &lt; .05). Bacterial abundance and beta diversity analysis showed differing microbiome changes in subjects who received omadacycline versus vancomycin.

Conclusions
Subjects given omadacycline had high fecal concentrations with a distinct microbiome profile compared to vancomycin.

Clinical Trials Registration
NCT06030219.
American Burn Association Clinical Practice Guidelines on Burn Shock Resuscitation
Authors: Cartotto Robert , Johnson Laura S , Savetamal Alisa , Greenhalgh David , Kubasiak John C , Pham Tam N , Rizzo Julie A , Sen Soman , Main Emilia 
Published: December 2023

Abstract
This Clinical Practice Guideline (CPG) addresses the topic of acute fluid resuscitation during the first 48 hours following a burn injury for adults with burns ≥20% of the total body surface area (%TBSA). The listed authors formed an investigation panel and developed clinically relevant PICO (Population, Intervention, Comparator, Outcome) questions. A systematic literature search returned 5978 titles related to this topic and after 3 levels of screening, 24 studies met criteria to address the PICO questions and were critically reviewed. We recommend that clinicians consider the use of human albumin solution, especially in patients with larger burns, to lower resuscitation volumes and improve urine output. We recommend initiating resuscitation based on providing 2 mL/kg/% TBSA burn in order to reduce resuscitation fluid volumes. We recommend selective monitoring of intra-abdominal and intraocular pressure during burn shock resuscitation. We make a weak recommendation for clinicians to consider the use of computer decision support software to guide fluid titration and lower resuscitation fluid volumes. We do not recommend the use of transpulmonary thermodilution-derived variables to guide burn shock resuscitation. We are unable to make any recommendations on the use of high-dose vitamin C (ascorbic acid), fresh frozen plasma (FFP), early continuous renal replacement therapy, or vasopressors as adjuncts during acute burn shock resuscitation. Mortality is an important outcome in burn shock resuscitation, but it was not formally included as a PICO outcome because the available scientific literature is missing studies of sufficient population size and quality to allow us to confidently make recommendations related to the outcome of survival at this time.
The rs6296 polymorphism in the 5-HT1b receptor in Dutch men with lifelong premature ejaculation: a genetic case-control association study
Authors: van Raaij Joost J , Janssen Paddy K C 
Published: December 2023

Abstract

Background
Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders.

Aim
In this study we sought to evaluate the genetic association between the rs6296 polymorphism of the 5-HT1b receptor and intravaginal ejaculation latency times (IELTs) in men with LPE compared with men in a control group.

Methods
This study was a prospective observational genetic case-control association study. The LPE definition of the International Society for Sexual Medicine (ISSM) 2013 was used. Patients were recruited in 2005-2009 while attending the department of Neurosexology, HagaZiekenhuis, the Netherlands. We obtained IELTs with the stopwatch method. Polymerase chain reaction (PCR) was used for genotyping rs6296. A randomly selected group of European Caucasian men from the 1000GENOMES project was used as a control group.

Outcomes
Study outcomes included results of comparisons of analysis of variance (ANOVA) tests between genotypes and IELTs in study participants, genotypes of cases and controls determined with the chi-square test, and expressions of allelotype- and genotype-specific risks for LPE determined with odds ratios.

Results
In total, 67 men with LPE were included in this study. The geometric mean (SD) IELT was 32.0 (27.4) seconds and was non-normally distributed. Genotype frequencies consisted of 29 (43.3%) GG, 31 (46.3%) GC, and 7(10.4%) CC individuals in the LPE group. Log-transformed IELTs were not statistically significant (per ANOVA tests) in men with GG, GC, or CC genotypes (P = .54). Genotype frequencies consisted of 16 (6.6%) GG; 93 (38.8%) GC, and 131 (54.6%) CC individuals in the control group (n = 240). Significant differences were found when comparing allele (P = 1.02e-17) and genotype (P = 3.22e-16) frequencies in cases and controls using a chi-square test. A statistically significant increased risk for LPE was found for carriers of the G allele (OR 5.62; 95% CI 4.13-9.42). Statistically significant risks were also found for the CG genotype (OR 6.24; 95% CI 2.63-14.77) and the GG genotype (OR 33.92; 95% CI 12.79-89.93).

Clinical implications
By investigating polymorphisms in target genes the neuro-pathophysiology of LPE could be further elaborated, potentially leading to more effective treatment.

Strengths and limitations
This is to our knowledge the first study investigating rs6296 with regard to LPE. By using a strict definition for LPE (ISSM 2013) and using the stopwatch method for measuring IELTs, bias in selection of true LPE patients will be relatively low. This study is limited by a relatively small study population and the lack of IELT data in the control group.

Conclusions
This study shows a genetic association in rs6296 in men with LPE compared with healthy controls. This result warrants attempted replication in future studies.
Mapping the Universe with gamma-ray bursts
Authors: Horvath Istvan , Bagoly Zsolt , Balazs Lajos G , Hakkila Jon , Horvath Zsuzsa , Joo Andras Peter , Pinter Sandor , Tóth L Viktor , Veres Peter , Racz Istvan I 
Published: December 2023

ABSTRACT
We explore large-scale cosmic structure using the spatial distribution of 542 gamma-ray bursts (GRBs) having accurately measured positions and spectroscopic redshifts. Prominent cosmological clusters are identified in both the northern and southern galactic hemispheres (avoiding extinction effects in the plane of the Milky Way) using the bootstrap point-radius method. The northern galactic hemisphere contains a significant group of four GRBs in the redshift range 0.59 ≤ z ≤ 0.62 (with a bootstrap probability of p = 0.012) along with the previously identified Hercules–Corona Borealis Great Wall (in the revised redshift range 0.9 ≤ z ≤ 2.1; p = 0.017). The southern galactic hemisphere contains the previously identified Giant GRB Ring (p = 0.022) along with another possible cluster of seven to nine GRBs at 1.17 ≤ z ≤ 1.444 (p = 0.031). Additionally, both the Hercules–Corona Borealis Great Wall and the Giant GRB Ring have become more prominent as the GRB sample size has grown. The approach used here underscores the potential value of GRB clustering as a probe of large-scale cosmic structure, complementary to galaxy and quasar clustering. Because of the vast scale on which GRB clustering provides valuable insights, it is important that optical GRB monitoring continues so that additional spectroscopic redshift measurements could be obtained.
Discovery of an extended GeV counterpart to the TeV source 1LHAASO J1945+2424 in Fermi-LAT data
Authors: Araya Miguel , Álvarez-Quesada J A 
Published: December 2023

ABSTRACT
With almost 15 yr of data taken by the Large Area Telescope (LAT) onboard the Fermi satellite we discovered an extended source of GeV emission in the region of the very high energy (TeV) source 1LHAASO J1945+2424. This TeV source is more extended than the LAT source. The spectrum of the GeV emission is hard (with a photon spectral index ∼1.5) and connects smoothly with that of the TeV source, indicating a likely common origin. In order to explain the origin of the γ-rays we explore scenarios that are typically used for supernova remnants (SNRs) and pulsar wind nebulae (PWNe). For an SNR with a single particle population, a leptonic particle distribution in the form of a broken power law with a break energy of ∼3.7 TeV explains the spectra well, while in the hadronic scenario a simple power law with a hard spectral index of ∼1.64 is necessary. In the PWN scenario, reasonable parameters are obtained for a source age of 10 kyr and current pulsar spin-down luminosity of ∼1034 erg s−1.
Differential roles of positive and negative supercoiling in organizing the E. coli genome
Authors: Fu Ziqi , Guo Monica S , Zhou Weiqiang , Xiao Jie 
Published: December 2023

Abstract
This study aims to explore whether and how positive and negative supercoiling contribute to the three-dimensional (3D) organization of the bacterial genome. We used recently published Escherichia coli GapR ChIP-seq and TopoI ChIP-seq (also called EcTopoI-seq) data, which marks positive and negative supercoiling sites, respectively, to study how supercoiling correlates with the spatial contact maps obtained from chromosome conformation capture sequencing (Hi-C and 5C). We find that supercoiled chromosomal loci have overall higher Hi-C contact frequencies than sites that are not supercoiled. Surprisingly, positive supercoiling corresponds to higher spatial contact than negative supercoiling. Additionally, positive, but not negative, supercoiling could be identified from Hi-C data with high accuracy. We further find that the majority of positive and negative supercoils coincide with highly active transcription units, with a minor group likely associated with replication and other genomic processes. Our results show that both positive and negative supercoiling enhance spatial contact, with positive supercoiling playing a larger role in bringing genomic loci closer in space. Based on our results, we propose new physical models of how the E. coli chromosome is organized by positive and negative supercoils.
Toxic comments are associated with reduced activity of volunteer editors on Wikipedia
Authors: Smirnov Ivan , Oprea Camelia , Strohmaier Markus 
Published: December 2023

Abstract
Wikipedia is one of the most successful collaborative projects in history. It is the largest encyclopedia ever created, with millions of users worldwide relying on it as the first source of information as well as for fact-checking and in-depth research. As Wikipedia relies solely on the efforts of its volunteer editors, its success might be particularly affected by toxic speech. In this paper, we analyze all 57 million comments made on user talk pages of 8.5 million editors across the six most active language editions of Wikipedia to study the potential impact of toxicity on editors’ behavior. We find that toxic comments are consistently associated with reduced activity of editors, equivalent to 0.5–2 active days per user in the short term. This translates to multiple human-years of lost productivity, considering the number of active contributors to Wikipedia. The effects of toxic comments are potentially even greater in the long term, as they are associated with a significantly increased risk of editors leaving the project altogether. Using an agent-based model, we demonstrate that toxicity attacks on Wikipedia have the potential to impede the progress of the entire project. Our results underscore the importance of mitigating toxic speech on collaborative platforms such as Wikipedia to ensure their continued success.
Genome Sequence of Alternaria tenuissima P1-2W Infecting Postharvest Kiwifruit
Authors: Ling Li-Zhen , Liu Zhen-Zhen , Zhang Shu-Dong 
Published: December 2023

Alternaria tenuissima can cause leaf spots and fruit decay in some economically important crops. Recently, this species was first reported as a causal agent causing fruit decay in postharvest kiwifruit. Here, a highly contiguous genome assembly 33.87 Mb in size was obtained by a combination of Illumina NovaSeq and PacBio SMRT sequencing methods, yielding five full chromosome-level sequences. This resource provides opportunities for a better understanding of the mechanisms that underpin the pathogenicity of A. tenuissima. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
GRP78 improves the therapeutic effect of mesenchymal stem cells on hemorrhagic shock‐induced liver injury: Involvement of the NF–кB and HO‐1/Nrf‐2 pathways
Authors: Han Jiahui , Jia Di , Yao Hao , Xu Ce , Huan Zhirong , Jin Hongdou , Ge Xin 
Published: December 2023

AbstractMesenchymal stem cells (MSCs) are a popular cell source for repairing the liver. Improving the survival rate and colonization time of MSCs may significantly improve the therapeutic outcomes of MSCs. Studies showed that 78‐kDa glucose‐regulated protein (GRP78) expression improves cell viability and migration. This study aims to examine whether GRP78 overexpression improves the efficacy of rat bone marrow‐derived MSCs (rBMSCs) in HS‐induced liver damage. Bone marrow was isolated from the femurs and tibias of rats. rBMSCs were transfected with a GFP‐labeled GRP78 expression vector. Flow cytometry, transwell invasion assay, scratch assay immunoblotting, TUNEL assay, MTT assay, and ELISA were carried out. The results showed that GRP78 overexpression enhanced the migration and invasion of rBMSCs. Moreover, GRP78‐overexpressing rBMSCs relieved liver damage, repressed liver oxidative stress, and inhibited apoptosis. We found that overexpression of GRP78 in rBMSCs inhibited activation of the NLRP3 inflammasome, significantly decreased the levels of inflammatory factors, and decreased the expression of CD68. Notably, GRP78 overexpression activated the Nrf‐2/HO‐1 pathway and inhibited the NF–κB pathway. High expression of GRP78 efficiently enhanced the effect of rBMSC therapy. GRP78 may be a potential target to improve the therapeutic efficacy of BMSCs.
Knowledge and Practice Gaps in Pediatric Neurocritical Care Nursing: Lessons Learned From a Specialized Educational Boot Camp
Authors: Chang Nathan , Sperber Amelia , Casazza May , Ciraulo Leslie , Teeyagura Prathyusha , Rasmussen Lindsey 
Published: December 2023

OBJECTIVES:
Pediatric neurocritical care (PNCC) is a quickly growing subspecialty within pediatric critical care medicine. Standards for care, education, and application of neuromonitoring technologies in PNCC are still being developed. We sought to identify and improve knowledge deficits in neurocritical care with an educational boot camp for nurses.

SETTING:
Quaternary children’s hospital with 36 PICU beds.

DESIGN:
Preinterventional and postinterventional study.

METHODS:
A 2-day boot camp course covering neurologic and neurosurgical topics pertinent to PNCC was provided to 46 pediatric acute and critical care nurses divided into three cohorts over 3 years. Participant characteristics were collected, and precourse and postcourse knowledge assessments were administered.

RESULTS:
Regarding participant characteristics, neither critical care registered nurse certification nor years of nursing experience were associated with better precourse baseline knowledge. Knowledge gaps spanned bedside neurologic assessments, physiologic goals in brain injury, and side effects of neurocritical care medications. In postcourse assessments, all participants showed improvement in scores, and most participants sustained improvements after 6 months. Nurses reported significant improvement in self-reported confidence in caring for the PNCC population. We also observed shorter ICU lengths of stay, decreased hospital incident reports, and decreased time to stroke imaging, although these programmatic metrics cannot be credited to nursing education alone.

CONCLUSIONS:
PNCC programs should include nursing expertise in the field. However, topics specific to PNCC may not be adequately addressed by existing general critical care nursing education and certification. A multimodal educational boot camp can be an effective method to improve nursing knowledge in PNCC. Our results demonstrate that specialty nursing education in PNCC is both innovative and feasible, with the potential to improve patient care. Further research is needed to determine the benefits of specialty education on quality of care and clinical outcomes.
Effect of CYP3A4*22, CYP3A5*3 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients
Authors: Ebid Abdel-Hameed IM , Ismail Dina A. , Lotfy Neama M. , Mahmoud Mohamed A. , El-Sharkawy Magdy 
Published: December 2023

Objective
This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.

Methods
One hundred thirty renal transplant patients placed on either tacrolimus or cyclosporine were recruited, where the effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on their dose requirements were studied at days 14, 30, and 90 post-transplantations.

Results
The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was significantly lower in the fast metabolizers group (CYP3A5*1/POR*28(CT/TT) carriers) than in the poor metabolizers group (CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) (P = 0.001, <0.001, and 0.003, respectively). Meanwhile, there was no significant effect of this gene combination on cyclosporine C0/D.

Conclusion
Combining the CYP3A5*3, POR*28, and CYP3A4*22 genotypes can have a significant effect on early tacrolimus dose requirements determination and adjustments. However, it does not have such influence on cyclosporine dose requirements.
Development of an ARMS multiplex real-time PCR assay for the detection of HLA-B*13:01 genotype by detecting highly specific SNPs
Authors: Yao Hao , Wang Kaixuan , Lu Sihai , Cao Fang , Dai Penggao 
Published: December 2023

Objectives
HLA-B*13:01 was strongly associated with Dapsone Hypersensitivity Syndrome (DHS). This study aimed to develop and validate a rapid and economical method for HLA-B*13:01 genotyping.

Methods
Two tubes multiplex real-time PCR detection system comprising amplification refractory mutation system primers and TaqMan probes was established for HLA-B*13:01 genotyping. Sequence-based typing was applied to validate the accuracy of the assay.

Results
The accuracy of the assay was 100% for HLA-B*13:01 genotyping. The detection limit of the new method was 0.025 ng DNA. The positive rate of HLA-B*13:01 in the Bouyei (20%, n = 50) populations was significantly higher than that in the Uighur population (4%, n = 100), Han (4.5%, n = 200), and Tibetan (1%, n = 100) (P < 0.05).

Conclusion
The proposed method is rapid and reliable for HLA-B*13:01 screening in a clinical setting.
Racial and ethnic differences and the role of unfavorable social determinants of health across steatotic liver disease subtypes in the United States
Authors: Ochoa-Allemant Pedro , Marrero Jorge A. , Serper Marina 
Published: December 2023

Background:
The global liver community established a more precise criteria to characterize steatotic liver disease (SLD), specifically metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated and alcohol-associated liver disease (MetALD). We aimed to estimate the burden of SLD subtypes and unfavorable social determinants of health (SDOH) in US adults and whether clinical and social factors drive disparities across racial/ethnic subgroups.

Methods:
We evaluated 4263 persons aged 20 years or older from the National Health and Nutrition Examination Survey 2017–2018. We estimated the weighted age-adjusted prevalence and severity of SLD, examined the prevalence of SDOH across SLD subtypes, and performed stepwise regression analysis to evaluate associations between race/ethnicity and SLD, accounting for metabolic risks, alcohol use, and SDOH.

Results:
Hispanic adults had the highest prevalence of MASLD (22.3%), MASLD-predominant MetALD (10.3%), alcohol-associated liver disease (ALD)-predominant MetALD (5.6%), and ALD (5.4%). Hispanic adults with MASLD had the highest prevalence of high-risk metabolic dysfunction–associated steatohepatitis (18.0%) and advanced fibrosis (21.1%), whereas non-Hispanic (NH) White adults with MetALD had the highest prevalence of high-risk metabolic dysfunction–associated steatohepatitis (19.3%), advanced fibrosis (19.5%), and cirrhosis (8.1%). Adults with ALD-predominant MetALD and ALD had an increased burden of unfavorable SDOH than those with MASLD, particularly food insecurity, limited health care access, and single living. In stepwise regression, the odds of SLD in Hispanic adults decreased after adjusting for metabolic risks (OR 1.40, 95% CI, 1.06–1.84) and alcohol use (OR 1.36, 95% CI, 1.01–1.82). Differences did not persist after adjusting for cumulative SDOH and nativity status (OR 1.22, 95% CI, 0.89–1.68).

Conclusions:
We found substantial disparities in the burden of unfavorable SDOH across SLD subtypes, particularly among those with ALD-predominant MetALD and ALD. Population-based approaches targeting SDOH may mitigate racial/ethnic differences among US adults with SLD.