bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncostatin M Induces a Pro-inflammatory Phenotype in Intestinal Subepithelial Myofibroblasts
Authors: Kokkotis Georgios , Filidou Eirini , Tarapatzi Gesthimani , Spathakis Michail , Kandilogiannakis Leonidas , Dovrolis Nikolas , Arvanitidis Konstantinos , Drygiannakis Ioannis , Valatas Vassilis , Vradelis Stergios , Manolopoulos Vangelis G , Paspaliaris Vasilis , Kolios George , Bamias Giorgos 
Published: May 2024

Abstract

Background
Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-α resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs.

Methods
The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1α/TNF-α. RNAseq data of mucosal biopsies were also analyzed.

Results
Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P &lt; .05), especially in inflamed segments (P &lt; .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1α/TNF-α (P &lt; .001; P &lt; .01; P &lt; .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P &lt; .001; P &lt; .05; P &lt; .001; P &lt; .001) and was further increased after prestimulation with IL-1α/TNF-α (P &lt; .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P &lt; .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P &lt; .001; P &lt; .001; P = .045; P = .033).

Conclusions
Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.
Pharmacologic Anticoagulation Is Associated With a Lower Risk of Recurrent Venous Thromboembolic Events During Janus Kinase Inhibitor Use for Patients With a Prior Thrombosis
Authors: Lowell Jeffrey A , Sharma Garvita , Swaminath Arun , Sultan Keith 
Published: May 2024

Abstract

Background
Janus kinase (JAK) inhibitors tofacitinib and upadacitinib are effective therapies for inflammatory bowel disease and rheumatologic disorders but currently possess a warning for increased venous thromboembolism (VTE) risk. Some patients with a history of VTE may benefit from a JAK inhibitor, but the risk of recurrent VTE with JAK inhibitor use is unclear. Our goal was to observe rates of new VTE events after starting JAK inhibitor therapy in patients with a prior VTE, and observe whether concurrent anticoagulation (AC) reduces this risk.

Methods
We conducted a review of adults prescribed tofacitinib or upadacitinib between January 1, 2000, and June 30, 2023, with a prior history of VTE. Patient charts were reviewed for demographic data, disease type, and VTE date(s), and to verify duration of JAK inhibitor use along with any concurrent AC. VTEs following JAK inhibitor initiation were identified by International Classification of Diseases–Tenth Revision code and verified by physician documentation and imaging.

Results
We identified 79 patients with a documented VTE history before initiating JAK inhibitors, 47 of whom began a JAK inhibitor with concurrent AC. Of these, 15 patients discontinued AC while receiving JAK inhibitors. In total, 5 new VTE events were observed during 55.42 patient-years of JAK inhibitor treatment without concurrent AC (9.0 events per 100 patient-years), while no new VTE events occurred during 65.2 patient-years of JAK inhibitor treatment with concurrent AC, demonstrating a lower risk of recurrent VTE (P = .020).

Conclusions
These results suggest that for patients with a prior VTE history there is a high risk for recurrent VTE while receiving JAK inhibitors. Concurrent use of AC with JAK inhibitors appears to be protective against recurrent VTEs in this population.
Antithrombotic therapy after heart valve surgery: contemporary practice in the UK
Authors: Laskar Nabila , Bayliss Christopher D , Kirmani Bilal H , Chambers John B , Maier Rebecca , Briffa Norman P , Cartwright Neil , Kendall Simon , Shah Benoy Nalin , Akowuah Enoch 
Published: May 2024

Abstract

OBJECTIVES
There is a lack of high-quality data informing the optimal antithrombotic drug strategy following bioprosthetic heart valve replacement or valve repair. Disparity in recommendations from international guidelines reflects this. This study aimed to document current patterns of antithrombotic prescribing after heart valve surgery in the UK.

METHODS
All UK consultant cardiac surgeons were e-mailed a custom-designed survey. The use of oral anticoagulant (OAC) and/or antiplatelet drugs following bioprosthetic aortic valve replacement or mitral valve replacement, or mitral valve repair (MVrep), for patients in sinus rhythm, without additional indications for antithrombotic medication, was assessed. Additionally, we evaluated anticoagulant choice following MVrep in patients with atrial fibrillation.

RESULTS
We identified 260 UK consultant cardiac surgeons from 36 units, of whom 103 (40%) responded, with 33 units (92%) having at least 1 respondent. The greatest consensus was for patients undergoing bioprosthetic aortic valve replacement, in which 76% of surgeons favour initial antiplatelet therapy and 53% prescribe lifelong treatment. Only 8% recommend initial OAC. After bioprosthetic mitral valve replacement, 48% of surgeons use an initial OAC strategy (versus 42% antiplatelet), with 66% subsequently prescribing lifelong antiplatelet therapy. After MVrep, recommendations were lifelong antiplatelet agent alone (34%) or following 3 months OAC (20%), no antithrombotic agent (20%), or 3 months OAC (16%). After MVrep for patients with established atrial fibrillation, surgeons recommend warfarin (38%), a direct oral anticoagulant (37%) or have no preference between the 2 (25%).

CONCLUSIONS
There is considerable variation in the use of antithrombotic drugs after heart valve surgery in the UK and a lack of high-quality evidence to guide practice, underscoring the need for randomized studies.
Stability of convergence rates: kernel interpolation on non-Lipschitz domains
Authors: Wenzel Tizian , Santin Gabriele , Haasdonk Bernard 
Published: May 2024

Abstract
Error estimates for kernel interpolation in Reproducing Kernel Hilbert Spaces usually assume quite restrictive properties on the shape of the domain, especially in the case of infinitely smooth kernels like the popular Gaussian kernel. In this paper we prove that it is possible to obtain convergence results (in the number of interpolation points) for kernel interpolation for arbitrary domains $\varOmega \subset{\mathbb{R}} ^{d}$, thus allowing for non-Lipschitz domains including e.g., cusps and irregular boundaries. Especially we show that, when going to a smaller domain $\tilde{\varOmega } \subset \varOmega \subset{\mathbb{R}} ^{d}$, the convergence rate does not deteriorate—i.e., the convergence rates are stable with respect to going to a subset. We obtain this by leveraging an analysis of greedy kernel algorithms. The impact of this result is explained on the examples of kernels of finite as well as infinite smoothness. A comparison to approximation in Sobolev spaces is drawn, where the shape of the domain $\varOmega $ has an impact on the approximation properties. Numerical experiments illustrate and confirm the analysis.
Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following Prior Infection or Vaccination
Authors: Ebinger Joseph E , Sun Nancy , Joung Sandy Y , Sanchez John Michael S , Wang Minhao , Liu Yunxian , Prostko John C , Frias Edwin C , Stewart James L , Heath Mallory , Claggett Brian L , Cheng Susan , Sobhani Kimia 
Published: May 2024

Abstract

Background
The extent to which infection versus vaccination has conferred similarly durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity during the Omicron era remains unclear.

Methods
In a cohort of 4496 adults under continued serological surveillance throughout the first year of Omicron-predominant SARS-CoV-2 transmission, we examined incidence of new infection among individuals whose last known antigenic exposure was either recent (&lt;90 days) or remote (≥90 days) infection or vaccination.

Results
We adjudicated 2053 new-onset infections occurring between 15 December 2021 through 22 December 2022. In multivariable-adjusted analyses, compared to individuals whose last known exposure was remote vaccination, those with recent vaccination (odds ratio [OR], 0.82 [95% confidence interval {CI}, .73–.93]; P = .002) or recent infection (OR, 0.14 [95% CI, .05–.45]; P = .001) had lower risk for new infection within the subsequent 90-day period. Given a significant age interaction (P = .004), we found that remote infection compared to remote vaccination was associated with significantly greater new infection risk in persons aged ≥60 years (OR, 1.88 [95% CI, 1.13–3.14]; P = .015) with no difference seen in those &lt;60 years (1.03 [95% CI, .69–1.53]; P = .88).

Conclusions
During the initial year of Omicron, prior infection and vaccination both offered protection against new infection. However, remote prior infection was less protective than remote vaccination for individuals aged ≥60 years. In older adults, immunity gained from vaccination appeared more durable than immunity gained from infection.
Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance
Authors: Costa Charlotte , Sirard Jean-Claude , Gibson Paddy S , Veening Jan-Willem , Gjini Erida , Baldry Mara 
Published: May 2024

Abstract
Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) improves the treatment of primary pneumonia or superinfection caused by AMX-sensitive or AMX-resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and antibiotic-resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. A mathematical model was developed that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.
Clinical and Microbial Determinants of Upper Respiratory Colonization With Streptococcus pneumoniae and Native Microbiota in People With Human Immunodeficiency Virus Type 1 and Control Adults
Authors: Nicholson Lindsay K , Kofonow Jennifer M , Robertson Charles E , Wright Timothy , Li Qing , Gardner Edward M , Frank Daniel N , Janoff Edward N 
Published: May 2024

Abstract

Background
The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among US adults with and without HIV-1 infection is not well characterized in the conjugate vaccine era.

Methods
We determined Spn colonization frequency by culture and specific lytA gene quantitative polymerase chain reaction (PCR) and microbiota profile by 16S ribosomal RNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics.

Results
The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; P = .46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (ie, β-diversity; NP: P = .0028, OP: P = .0098), decreased α-diversity (NP: P = .024, OP: P = .0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered β-diversity in the nasopharynx (P = .011) but not oropharynx (P = .21).

Conclusions
Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the preconjugate era. The persistently increased risk of pneumococcal disease despite antiretroviral therapy may relate to behavioral and immunologic variables other than colonization.
Prevalence and Genetic Diversity of Adenovirus 40/41, Astrovirus, and Sapovirus in Children With Acute Gastroenteritis in Kansas City, 2011–2016
Authors: Diez-Valcarce Marta , Cannon Jennifer L , Browne Hannah , Nguyen Kenny , Harrison Christopher J , Moffatt Mary E , Weltmer Kirsten , Lee Brian R , Hassan Ferdaus , Dhar Debarpan , Wikswo Mary E , Payne Daniel C , Curns Aaron T , Selvarangan Rangaraj , Vinjé Jan 
Published: May 2024

Abstract

Background
Most acute gastroenteritis (AGE) episodes in children in the United States are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus, or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children.

Methods
We tested and typed stool specimens collected between December 2011 and June 2016 from 1 NVSN site in Kansas City for the 3 viruses, and calculated hospitalization and emergency department (ED) detection rates.

Results
Of 3205 collected specimens, 2453 (76.5%) were from AGE patients (339 inpatients and 2114 ED patients) and 752 (23.5%) were from healthy controls. In patients with AGE, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%), and AdV40/41 in 101 (4.5%) of 2249 patients. In healthy controls, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent. Hospitalization rates were 5 (AdV40/41), 4 (astrovirus), and 8 (sapovirus) per 100 000 children &lt;11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus), and 5.3 (sapovirus) per 1000 children &lt;5 years old.

Conclusions
Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.
Shocks and Stability of Risk and Time Preferences among Poor Rural Households in Ethiopia
Authors: Meles Tensay Hadush , Abay Mehari Hiluf , Berhane Guush , Taffesse Alemayehu Seyoum 
Published: May 2024

Abstract
This paper examines the effects of shocks on temporal stability of risk and time preferences of rural households within a developing country context characterized by frequent droughts, chronic food insecurity, and low levels of education. Leveraging a three-wave large and diverse household panel data that elicits preferences every two years for more than 6,500 individuals from over 5,600 sample rural households in Ethiopia, we analyze the effects of droughts (self-reported) and rainfall shortfalls on household risk and time preferences. Our findings show that households become more risk-averse and impatient after experiencing drought and rainfall shocks; the change in risk preferences is more notable among households that experience recurrent droughts and multiple covariate shocks during the same period.
211 Analysis of microbial communities from a commercial-size swine manure pit and their association with production of volatile organic compounds
Authors: Fowler Emily , Samuel Ryan S , St-Pierre Benoit 
Published: May 2024

Abstract
Global pollution and emission concerns have been linked to concentrated animal feeding operations (CAFOs). Indeed, the U.S Environmental Protection Agency (US EPA) warns that there is a significant danger to human health, soil, and water quality from CAFOs. Volatile organic compounds (VOCs), which are amongst air contaminants that pose a serious risk, are abundantly produced in swine manure pits. While VOC emissions from swine manure have been well studied, the microbial species responsible for their production remain mostly uncharacterized. Thus, a deeper comprehension of the microorganisms responsible for VOC production in swine manure pits may help in the development of management approaches that target the microbiome in these environments. In this context, this study aimed to identify the major bacterial species populating the manure pit of a commercial-size swine wean-to-finish research facility. Manure collected from two sampling locations at different time points were analyzed using the 16S rRNA gene through PCR-amplification of the V1-V3 regions from microbial genomic DNA, followed by Illumina MiSeq 2X300 sequencing. An analysis of the most highly represented microorganisms identified 24 bacterial Operational Taxonomic Units (OTUs), with only four showing a species-level nucleotide sequence identity to currently known or valid species. As these results indicated that the majority of bacterial species from this manure pit were unknown, a metagenomics approach was used to assemble partial to full length genomes from the two most abundant OTUs: Pit_9-00239 [5.09% - 19.44%; Clostridium saccharoperbutylacetonicum (96.60%)] and Pit_ 7-00035 [5.58% - 17.30%; Bacteroides eggerthii (87.66%)]. From genome assembly analysis, 979 contigs were generated for a combined length of 12,367,510 bp, which together included 21,776 coding sequences. Predicted metabolic functions from these contig sets included pathways involved in carbohydrate utilization (glycolysis), vitamin synthesis (riboflavin), and butyrate production (volatile fatty acids). Notably, an enzyme responsible for the production of indole, a common VOC produced from swine manure pits, was also identified. Together, the results from this analysis provide insights on metabolic capabilities of abundant bacterial species from manure pits. These can in turn be used for the future development of management strategies or products that can reduce VOC emissions that result from swine CAFO manure storage.
118 Gene editing: A European perspective
Authors: Gil Maria Antonia 
Published: May 2024

Abstract
Gene editing by CRISPR/Cas has revolutionized numerous facets of biotechnology within a remarkably short period of time. Its combined use with either somatic cell nuclear transfer or microinjection into fertilized oocytes is highly useful for mutating genes in a very precise and specific manner. This technology has profoundly transformed the world of animal research, particularly for biomedical and productive applications. Gene editing can now be applied to animal modeling and therapeutic research, bringing us closer to the possibility of using animals as organ donors for xenotransplantation. Furthermore, it has become an effective tool in animal production for purposes such as increasing disease tolerance or resistance and enhancing animal welfare.
In this presentation, we will explore how this genome editing tool has influenced the research conducted in Europe, examining the current landscape and addressing the challenges, with a special focus on pigs. We will also discuss the regulation of gene-edited animals in the EU.
226 Oral and rumen microbiome characterization to predict host phenotypes
Authors: Adams Seidu , Spangler Matthew L , Fernando Samodha 
Published: May 2024

Abstract
Studies have utilized rumen microbiome composition and function to predict animal phenotypes. Yet, sample collection for rumen microbial community analysis can be difficult and invasive and hinders the possibility of sampling large animal populations. In this study, we investigated the development of the bovine rumen microbiome over time, to identify the potential of the oral microbiome as a proxy for the rumen microbiome, and to test the applicability of using the oral microbiome for predicting phenotypes in beef cattle. We employed 16S rRNA amplicon sequencing to characterize the rumen and oral bacterial community structure over time and collected both birth and weaning weights in a population of 220 animals. Our findings show that both the oral and rumen microbiomes are established early, and a significant portion of the taxa persists even after weaning. We identified a group of core successional species shared between the oral and rumen bacterial communities, which are established early and persist over time. The oral bacterial community was dominated by phyla Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteria, while the rumen bacterial community was dominated by phyla Bacteroidota, Firmicutes, Verrucomicrobia, Fibrobacteria, and Spirochaetota. Furthermore, we observed that 38% of Amplicon Sequence Variants (ASVs) were shared between the oral and rumen microbiomes at 50 to 120 d of age. At 170 to 240 d of age, 37% of ASVs were shared, and at 295 to 365 d, 33% of ASVs were shared. Finally, at 400 to 468 d, 21% of ASVs were shared. Based on weighted Unifrac analysis, notable differences and distinct clustering was observed between oral and rumen microbiome communities at different sampling ages (P = 0.001; R2 = 0.50969, 50 to 120; P = 0.001; R2 = 0.66247, 170 to 240; P = 0.001; R2 = 0.62036, 295 to 365; and P = 0.001, R2 = 0.66559, 400 to 468). Microbiability estimates varied across different stages and microbial environments. For the oral bacterial community at 50 to 120, the estimates were 0.029%, 0.032%, 0.029%, and 0.028% for birth weight, weaning weight, intramuscular fat (IMF), and ribeye area (REA), respectively. In contrast, the rumen microbiome exhibited microbiability values of 0.034%, 0.058, 0.059, and 0.069% for birth weight, weaning weight, IMF, and REA respectively during the same period. As the animal aged the microbiability increased. At 170 to 240, oral microbiomes showed microbiability estimates of 0.051%, 0.060%, 0.069%, and 0.21% for birth weight, weaning weight, IMF, and REA respectively. In comparison, the rumen microbiome displayed greater microbiability estimates of 0.12%, 0.124%, 0.20%, and 0.26% for birth weight, weaning weight, IMF, and REA respectively. In conclusion, the oral microbiome is not a good proxy for the rumen microbiome composition; however, there is potential to use the oral microbiome for phenotype prediction.