bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose xenogeneic mesenchymal stem cells target canine osteoarthritis through systemic immunomodulation and homing
Authors: Beerts Charlotte , Broeckx Sarah Y. , Depuydt Eva , Tack Liesa , Van Hecke Lore , Chiers Koen , Van Brantegem Leen , Braun Gabriele , Hellmann Klaus , de Bouvre Nathalie , Van Bruaene Nathalie , De Ryck Tine , Duchateau Luc , Van Ryssen Bernadette , Peremans Kathelijne , Saunders Jimmy H. , Verhoeven Geert , Pauwelyn Glenn , Spaas Jan H. 
Published: October 2023

AbstractBackgroundAs current therapies for canine osteoarthritis (OA) provide mainly symptomatic improvement and fail to address the complex pathology of the disease, mesenchymal stem cells (MSCs) offer a promising biological approach to address both aspects of OA through their immunomodulatory properties.MethodsThis study aimed to investigate the safety and efficacy of xenogeneic MSCs in dogs with OA at different dose levels after intravenous injection. OA was surgically induced in the right stifle joint. Thirty-two male and female dogs were divided into three treatment groups and a control group. Regular general physical examinations; lameness, joint, radiographic, and animal caretaker assessments; pressure plate analyses; and blood analyses were performed over 42 days. At study end, joint tissues were evaluated regarding gross pathology, histopathology, and immunohistochemistry. In a follow-up study, the biodistribution of intravenously injected99mTc-labeled equine peripheral blood-derived MSCs was evaluated over 24h in three dogs after the cruciate ligament section.ResultsThe dose determination study showed the systemic administration of ePB-MSCs in a canine OA model resulted in an analgesic, anti-inflammatory, and joint tissue protective effect associated with improved clinical signs and improved cartilage structure, as well as a good safety profile. Furthermore, a clear dose effect was found with 0.3 × 106ePB-MSCs as the most effective dose. In addition, this treatment was demonstrated to home specifically towards the injury zone in a biodistribution study.ConclusionThis model-based study is the first to confirm the efficacy and safety of systemically administered xenogeneic MSCs in dogs with OA. The systemic administration of a low dose of xenogeneic MSCs could offer a widely accessible, safe, and efficacious treatment to address the complex pathology of canine OA and potentially slow down the disease progression by its joint tissue protective effect.
Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment
Authors: Duffy Shannon C. , Lupien Andréanne , Elhaji Youssef , Farag Mina , Marcus Victoria , Behr Marcel A. 
Published: October 2023

AbstractMycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease remains widespread in part due to the limitations of available diagnostics and vaccines. A representative small animal model of disease could act as a valuable tool for studying its pathogenesis and to develop new methods for paratuberculosis control, but current models are lacking. Streptomycin pre-treatment can reduce colonization resistance and has previously been shown to improve enteric infection in a Salmonella model. Here, we investigated whether streptomycin pre-treatment of mice followed by MAP gavage could act as a model of paratuberculosis which mimics the natural route of infection and disease development in ruminants. The infection outcomes of MAP were compared to M. avium subsp. hominissuis (MAH), an environmental mycobacterium, and M. bovis and M. orygis, two tuberculous mycobacteria. Streptomycin pre-treatment was shown to consistently improve bacterial infection post-oral inoculation. This model led to chronic MAP infection of the intestines and mesenteric lymph nodes (MLNs) up to 24-weeks post-gavage, however there was no evidence of inflammation or disease. These infection outcomes were found to be specific to MAP. When the model was applied to a bacterium of lesser virulence MAH, the infection was comparatively transient. Mice infected with bacteria of greater virulence, M. bovis or M. orygis, developed chronic intestinal and MLN infection with pulmonary disease similar to zoonotic TB. Our findings suggest that a streptomycin pre-treatment mouse model could be applied to future studies to improve enteric infection with MAP and to investigate other modifications underlying MAP enteritis.
Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells
Authors: Perez-Garcia Javier , Pino-Yanes Maria , Plender Elizabeth G. , Everman Jamie L. , Eng Celeste , Jackson Nathan D. , Moore Camille M. , Beckman Kenneth B. , Medina Vivian , Sharma Sunita , Winnica Daniel Efrain , Holguin Fernando , Rodríguez-Santana José , Villar Jesús , Ziv Elad , Seibold Max A. , Burchard Esteban G. 
Published: October 2023

Abstract
Background
Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables.

Results
We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10–8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10–5). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR] < 0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p = 0.030). DNAm changes in these three CpGs were shown to be influenced by three independent genetic variants (FDR < 0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30 × 10–14 ≤ p ≤ 6.60 × 10–5). Additionally, hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with increased gene expression of the genes where they are located (FDR < 0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p = 0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p value < 0.05).

Conclusions
This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.
Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection
Authors: Duan Honglei , Wang Xu , Qi Wenqian , Shi Jingyi , Han Liang , Wang Guohua , Xu Yanhui , Liu Jia , Wang Jiangbin 
Published: October 2023

Abstract
Background
To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.

Methods
A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.

Results
Two SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis.

Conclusions
This study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.
Predominance of low pathogenic avian influenza virus H9N2 in the respiratory co-infections in broilers in Tunisia: a longitudinal field study, 2018–2020
Authors: Jbenyeni Adam , Croville Guillaume , Cazaban Christophe , Guérin Jean-Luc 
Published: October 2023

AbstractRespiratory diseases are a health and economic concern for poultry production worldwide. Given global economic exchanges and migratory bird flyways, respiratory viruses are likely to emerge continuously in new territories. The primary aim of this study was to investigate the major pathogens involved in respiratory disease in Tunisian broiler poultry and their epidemiology. Between 2018 and 2020, broilers farms in northeastern Tunisia were monitored, and 39 clinically diseased flocks were sampled. Samples were screened for five viral and three bacterial respiratory pathogens using a panel of real-time PCR assays. The reemergence of H9N2 low pathogenic avian influenza virus (LPAIV) in commercial poultry was reported, and the Northern and Western African GI lineage strain was typed. The infectious bronchitis virus (IBV) GI-23 lineage and the avian metapneumovirus (aMPV) subtype B also were detected for the first time in broilers in Tunisia. H9N2 LPAIV was the most detected pathogen in the flocks tested, but rarely alone, as 15 of the 16 H9N2 positive flocks were co-infected. Except for infectious laryngotracheitis virus (ILTV), all of the targeted pathogens were detected, and in 61% of the respiratory disease cases, a combination of pathogens was identified. The major combinations were H9N2 + aMPV (8/39) and H9N2 + IBV (6/39), showing the high contribution of H9N2 LPAIV to the multifactorial respiratory diseases. This field survey provided evidence of the emergence of new respiratory viruses and the complexity of respiratory disease in Tunisia. A comprehensive and continuous surveillance strategy therefore is needed to better control respiratory pathogens in Tunisia.
Bioactive metabolites identified from Aspergillus terreus derived from soil
Authors: Fayek Menna , Ebrahim Hassan Y. , Abdel-Aziz Mohamed S. , Taha Heba , Moharram Fatma A. 
Published: October 2023

AbstractAspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and peptides. In addition, a new triglyceride (1) and a diketopiperazine derivative namely asterrine (4), together with two known butyrolactone (2–3) were purified from the extract. The chemical skeleton of the purified compounds was established by comprehensive analysis of their ESI/MS, 1 and 2D-NMR data. The extract and compounds 3,4 exhibited a strong inhibitory activity for the binding of ACE2 to SARS-CoV-2 spike-protein receptor with IC50 7.4, 9.5, and 8.5 µg/mL, respectively. In addition, the extract, 1 and 2 displayed a potent anti-inflammatory effect with IC50 51.31 and 37.25 pg/mL (Il-6) and 87.97, 68.22 pg/mL (TNF-α), respectively, in comparison to LPS control. In addition, the extract and compound 4 displayed an antimicrobial effect towards S. aureus by MIC 62.5 and 125 μg/mL, while the extract exhibited a potent effect against C. albicans (MIC of 125 μg/mL). Collectively, our data introduce novel bioactivities for the secondary metabolites produced by the terrestrial fungus Aspergillus terreus.
Strong pollen limitation in genetically uniform hybrid chestnut orchards despite proximity to chestnut forests
Authors: Larue Clément , Petit Rémy J. 
Published: October 2023

Abstract
Key message
In arboriculture, the number and diversity of pollen donors can have a major impact on fruit production. We studied pollination insurance in hybrid chestnut orchards (C. sativa × C. crenata) provided by nearby wild European chestnuts (C. sativa) in southwestern France. Most fruits were sired by hybrid pollenizers rather than by wild chestnuts. When these hybrid pollenizers were too scarce, a frequent situation, pollen produced by wild chestnut trees did not compensate for the lack of compatible pollen and fertilization rates and fruit production collapsed.

Context
The demand for chestnuts has been increasing in recent years in many European countries, but fruit production is not sufficient to meet this demand. Improving pollination service in chestnut orchards could increase fruit production.

Aims
Investigate pollination service in chestnut orchards. Evaluate the contribution to pollination of trees growing in chestnut woods and forests.

Methods
We investigated five orchards planted with hybrid chestnuts (C. sativa × C. crenata) cultivars in southwestern France. We combined fruit set data, which provide information about pollination rate, with genetic data, which provide information about pollen origin. We used this information to estimate the contribution of nearby C. sativa forest stands to the pollination of each orchard.

Results
Pollination rates vary considerably, being fivefold higher in orchards comprising numerous pollen donors than in monovarietal orchards. Because of asymmetric hybridization barriers between hybrid and purebred cultivars, the surrounding chestnut forests provide very limited pollination insurance: less than 14% of the flowers in these monovarietal orchards had been pollinated by forest trees.

Conclusion
Because chestnut orchards are now increasingly relying on hybrid cultivars, surrounding wild European chestnut trees are no longer a reliable pollen source. To achieve maximal fruit set, efforts must therefore concentrate on orchard design, which should include enough cultivar diversity.
Remarks on a fractional nonlinear partial integro-differential equation via the new generalized multivariate Mittag-Leffler function
Authors: Li Chenkuan , Saadati Reza , Beaudin Joshua , Hrytsenko Andrii 
Published: October 2023

AbstractIntroducing a new generalized multivariate Mittag-Leffler function which is a generalization of the multivariate Mittag-Leffler function, we derive a sufficient condition for the uniqueness of solutions to a brand new boundary value problem of the fractional nonlinear partial integro-differential equation using Banach’s fixed point theorem and Babenko’s technique. This has many potential applications since uniqueness is an important topic in many scientific areas, and the method used clearly opens directions for studying other types of equations and corresponding initial or boundary value problems. In addition, we use Python which is a high-level programming language efficiently dealing with the summation of multi-indices to compute approximate values of the generalized Mittag-Leffler function (it seems impossible to do so by any existing integral representation of the Mittag-Leffler function), and provide an example showing applications of key results derived.
Concrete Made with Partial Substitutions of Wheat Straw Ash: A Review
Authors: Ahmad Jawad , Arbili Mohamed Moafak , Alqurashi Muwaffaq , Althoey Fadi , Deifalla Ahmed Farouk 
Published: October 2023

AbstractMany scientists are now focusing their attention on the utilization of valuable industrial or agricultural wastes as the primary raw material for the construction sector. These wastes, on the other hand, are affordable and readily accessible, making them ideal for commercial use while also contributing to the reduction of environmental degradation. Wheat straw ash (WTSA) is a kind of agricultural waste that has the potential to be utilized in concrete. Although many researchers are focused on utilization of WTSA in concrete. However, an updated review is required which provides easy access for the reader to get an idea about the benefits of WTSA in concrete. Therefore, this study provides a comprehensive review of the utilization of WTSA as a concrete ingredient. Physical and chemical compositions of WTSA, flowability, mechanical strength (compressive, flexure, tensile strength, and elastic modulus), and durability properties (permeability, carbonation, ultrasonic pulse velocity, alkali-silica reaction and chloride attacks) are the main aspects of this review. Results indicate that the performance of concrete improved with partial substitutions of cement with WTSA but simultaneously decreased the flowability of concrete. The optimum dose is important as higher dose results in decreased mechanical strength. The typical optimum dose ranges from 10 to 20% by weight of the binder. The performance of concrete in terms of durability was also improved but less research is carried out on the durability performance of concrete with WTSA. Additionally, despite WTSA's improvement in mechanical strength, concrete still exhibits lower tensile strain, which leads to brittle failure. Therefore, it was recommended that further study should be done to increase its tensile strength.
The impact of HCV eradication using interferon-free direct acting antivirals on bone-mineral, anemia parameters and peripheral insulin resistance in hepatitis c-infected Egyptian hemodialysis cohort
Authors: Elnokeety Mahmoud M. , Darwish Rasha Ahmed , Hegazy Mohamed Tharwat , Abouzeid Sameh , Fayed Ahmed 
Published: October 2023

Abstract
Background
Hepatitis C virus (HCV) infection is linked to a higher mortality rate in hemodialysis (HD) patients. We aimed to see if HCV eradication using interferon-free direct acting antivirals (DAAs) can affect bone-mineral and anemia biochemical parameters such as serum calcium (Ca++), phosphorus (PO4+), parathormone (PTH), fibroblast growth factor 23 (FGF23), hemoglobin (HB), and ferritin in HD patients and also peripheral insulin resistance by monitoring serum fasting insulin and HOMA insulin resistance (HOMA-IR).

Methods
Three hundred and thirty-four adults on regular HD with positive HCV genotype 4 (191 male and 143 female) were included; 157 of them had seroconversion during HD. All were hepatitis B virus (HBV) negative and received treatment with DAAs. All cases were examined for body mass index (BMI), HB, ferritin level, transferrin saturation (TSAT), Ca++, PO4+, PTH, FGF23, serum albumin, alanine transaminase (ALT), fasting insulin level, and HOMA-IR at the beginning and then were measured after 6 and 12 months from a sustained virological response (SVR).

Results
After 6 and 12 months from SVR, there was a significant increase in serum Ca despite no change in oral calcium dose requirement over that period (p = 0001), a significant increase in HB, serum iron (p = 0001), and a significant reduction in serum ferritin, PO4, PTH, and FGF23 (p = 0001). Both fasting insulin level and HOMA-IR were statistically significantly dropped.

Conclusion
HCV eradication with interferon-free DAAs showed a statistically significant impact on hemodialysis patients regarding hemoglobin, ferritin level, bone-mineral parameters, and improvement in peripheral insulin resistance.
Impact of clonal hematopoiesis in COVID-19 patients at high risk for adverse clinical outcomes
Authors: Smith Cathy , Burugula Bala B. , Jones Morgan A. , Li Qing , Kitzman Jacob O. , Wong Terrence N. 
Published: October 2023

Abstract
Purpose
Clonal hematopoiesis (CH) describes the aging-associated expansion of mutant hematopoietic cell populations. In various cohorts, CH has been associated with increased morbidity and mortality from non-hematologic diseases such as cardiovascular disease and infections, including COVID-19. Comorbidities placing individuals at risk of complications from these disorders, such as diabetes, also increase in prevalence with age and frequently co-exist with CH. How CH interacts with other aging-associated comorbidities to impact human health remains unknown.

Methods
We assessed the impact of CH on the pre-existing end-organ damage and ultimate clinical outcomes among 242 patients hospitalized with COVID-19 at Michigan Medicine from March to June of 2020. In contrast to most previous studies, these patients skewed older with the majority having multiple comorbidities, which placed them at higher risk for end-organ damage and poor clinical outcomes.

Results
Overall CH was not significantly associated with increased COVID-19 mortality after controlling for other risk factors, although we did note a borderline-significant association specifically for non-DNMT3A CH mutations. In contrast, we observed a significant association between CH and pre-existing chronic kidney disease (CKD), which was strongest for DNMT3A mutant CH.

Conclusions
These data suggest that the clinical impact of CH is influenced by the specific gene(s) mutated and is further modified by other comorbidities and clinical risk factors frequently present in the elderly.