bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy
Authors: Li Xiang , Xie Han , Chao Jia-jing , Jia Yuan-Hui , Zuo Jia , An Yan-peng , Bao Yi-Rong , Jiang Xiang , Ying Hao
Published: October 2023

Background

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.

Methods

We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.

Results

An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.

Conclusions

Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.
Comparison of different ratios of propofol-ketamine admixture in rapid-sequence induction of anesthesia for emergency laparotomy: a randomized controlled trial
Authors: Elsherbiny Mona , Hasanin Ahmed , Kasem Sahar , Abouzeid Mohamed , Mostafa Maha , Fouad Ahmed , Abdelwahab Yaser
Published: October 2023

Background

We aimed to compare the hemodynamic effect of two ratios of propofol and ketamine (ketofol), namely 1:1 and 1:3 ratios, in rapid-sequence induction of anesthesia for emergency laparotomy.

Methods

This randomized controlled study included adult patients undergoing emergency laparotomy under general anesthesia. The patients were randomized to receive either ketofol ratio of 1:1 (n = 37) or ketofol ratio of 1:3 (n = 37). Hypotension (mean arterial pressure < 70 mmHg) was managed by 5-mcg norepinephrine. The primary outcome was total norepinephrine requirements during the postinduction period. Secondary outcomes included the incidence of postinduction hypotension, and the intubation condition (excellent, good, or poor).

Results

Thirty-seven patients in the ketofol-1:1 and 35 patients in the ketofol 1:3 group were analyzed. The total norepinephrine requirement was less in the ketofol-1:1 group than in the ketofol-1:3 group, P-values: 0.043. The incidence of postinduction hypotension was less in the ketofol-1:1 group (4 [12%]) than in ketofol-1:3 group (12 [35%]), P-value 0.022. All the included patients had excellent intubation condition.

Conclusion

In patients undergoing emergency laparotomy, the use of ketofol in 1:1 ratio for rapid-sequence induction of anesthesia was associated with less incidence of postinduction hypotension and vasopressor consumption in comparison to the 1:3 ratio with comparable intubation conditions.

Clinical trial registration

NCT05166330. URL: https://clinicaltrials.gov/ct2/show/NCT05166330.
Effects of oral health-related quality of life on total mortality: a prospective cohort study
Authors: Arimoto Nishiki , Nishimura Rumi , Kobayashi Teruo , Asaeda Mayuka , Naito Toru , Kojima Masaaki , Umemura Osami , Yokota Makoto , Hanada Nobuhiro , Kawamura Takashi , Wakai Kenji , Naito Mariko
Published: October 2023

Background

The effects of oral health on mortality have been reported; however, the association between mortality and Oral Health-Related Quality of Life (OHQOL) is unknown. We investigated the effect of OHQOL on total mortality in a cohort consisting of dentists.

Methods

In this cohort study, we analyzed data from the Longitudinal Evaluation of Multi-phasic, Odonatological and Nutritional Associations in Dentists study. We conducted a baseline survey of general and oral health factors. We called for 31,178 participants and collected responses from 10,256 participants. We followed up with 10,114 participants (mean age ± standard deviation, 52.4 ± 12.1 years; females, 8.9%) for 7.7 years, until March 2014, to determine the average total mortality. OHQOL was assessed using the General Oral Health Assessment Index (GOHAI). The total score was divided into quartiles (Q1 ≤ 51.6, Q2 = 51.7–56.7, Q3 = 56.8–59.9, and Q4 = 60.0), with higher GOHAI scores indicating better OHQOL (score range, 12–60). The association between OHQOL and total mortality was analyzed using the Cox proportional hazards model.

Results

We documented 460 deaths. Males with low GOHAI scores possessed a remarkably high risk of total mortality. The multivariate adjusted-hazard ratios (aHRs), were 1.93 (95% confidence interval [CI], 1.07 − 3.48) for Q1, 1.69 (95% CI, 0.90 − 3.17) for Q2, and 0.65 (95% CI, 0.29 − 1.46) for Q3, relative to Q4 (trend p = 0.001). The aHRs in the multivariate model with all background variables were 1.69 (95% CI, 1.15–2.46) for Q1, 1.53 (95% CI, 1.04–2.27) for Q2, and 1.09 (95% CI, 0.71–1.70) for Q3, relative to Q4 (trend p = 0.001). In females, there was no significant association between the quartiles, in both the multivariate-adjusted model (trend p = 0.52) and multivariate-adjusted model with all background variables (trend p = 0.79).

Conclusions

A lower OHQOL indicated an increased risk of total mortality in dentists. OHQOL may be used as an indicator for selecting treatment plans and personalized care interventions, thus contributing to increased healthy life expectancy.

Trial registration

Aichi Cancer Center, Nagoya University Graduate School of Medicine, and Hiroshima University (Approval numbers: 33, 632–3, 8–21, and E2019-1603).
Outpatient education, a momentous in clinical education: a qualitative study of medical students’, faculty members’, and residents’ perspectives
Authors: Barzegar Marziyeh , Faghihi Seyed Aliakbar , Amini Mitra , Zarifsanaiey Nahid , Boushehri Elham
Published: October 2023

Background

Even though a lot of scholars have been looking at outpatient education lately because it has become more popular and they want to know about its successes, failures, and problems, we have not been able to find a complete study. Therefore, our study aims to gain a deeper understanding of the various aspects of outpatient education based on the actual experiences of medical students, faculty, and residents.

Methods

Face-to-face and semi-structured interviews were used to collect data for this qualitative study. Until data saturation was reached, the interviews continued. A total of 21 participants from Shiraz University of Medical Sciences, including medical students, residents, and teachers, were enrolled. The Guba and Lincoln-first written standards for scientific accuracy in qualitative research were used to figure out how reliable the data were.

Results

Fourteen categories were extracted from four main themes. The results show that four categories: “physical space and equipment,” “prerequisites related to the curriculum,” “teaching skills development,” and “near-peer teachers” should be considered for outpatient education preparation. Theme 2, “implementation requirements,” included “student dimension,” “faculty’s commitment to planning,” and “program supervision.” Theme 3, “challenges of outpatient education,” was described by five related categories, including “curriculum implementation challenges,” “student challenges,” “faculty challenges,” “system-related challenges,” and “patient-related challenges.” Finally, two categories emerged about facilitators of outpatient education: internal and external facilitators.

Conclusion

Outpatient clinics represent a crucial aspect of medical practice. To effectively leverage this resource, preliminary planning, considering all the prerequisites, paying attention to the implementation requirements, getting to know the challenges, and trying to solve them, especially with incentives, are essential.
Including audience response systems in debriefing. A mixed study during nursing simulation-based learning
Authors: Molina-Rodríguez Alonso , Suárez-Cortés María , Leal-Costa César , Ruzafa-Martínez María , Díaz-Agea José Luis , Ramos-Morcillo Antonio Jesús , Jiménez-Ruiz Ismael
Published: October 2023

Background

The audience response systems are being implemented to support active learning in nursing degree programs. The benefits of audience response systems have been studied in lecture-based classes and seminars, but their advantages or inconveniences when included in the debriefing phase of a high-fidelity clinical simulation have not been explored. The study aim was to discover student´s experience about using of interactive questions during debriefing, and the self-perceived effects on attention, participation and motivation.

Methods

A Mixed-methods study was used exploratory sequential design in a university. The participants were 4th-year students enrolled in the Nursing Degree in a university in Southern Spain. (1) Qualitative phase: a phenomenological approach was utilized, and focus groups were used for data-collection. (2) Quantitative phase: cross-sectional descriptive study using a questionnaire designed “ad hoc”, on the experiences on the use of interactive questions in the debriefing phase and the Debriefing Experience Scale.

Results

(1) Qualitative phase: the students highlighted the facilitating role of the interactive questions during the reflection part of the debriefing, and mentioned that the interactive questions helped with stimulating attention, participation, and motivation during the analytical part of the debriefing; (2) Quantitative phase: it was observed that the best evaluated dimension was “Motivation”, with a mean of 4.7 (SD = 0.480), followed by the dimension “Participation”, with a mean of 4.66 (SD = 0.461), and lastly, the dimension “Attention”, with a mean of 4.64 (SD = 0.418).

Conclusions

The use of interactive questions contributed the attention, participation, and motivation of the students during the debriefing, contributing towards a highly satisfactory experience of high-fidelity clinical simulation.
Zoonotic diseases: understanding the risks and mitigating the threats
Authors: Elsohaby Ibrahim , Villa Luca
Published: October 2023

Zoonotic diseases are like a sneaky game of “tag” between animals and humans, where the stakes are high and the consequences can be deadly. From the bubonic plague to COVID-19, zoonotic diseases have affected humanity for centuries, reminding us of our interconnectedness with the animal kingdom and the importance of taking proactive measures to prevent their spread. Whether it is avoiding contact with animals or practicing good hygiene, staying safe from zoonotic diseases is a game we all need to play.
Causal effects of gut microbiome on autoimmune liver disease: a two-sample Mendelian randomization study
Authors: Fu Yugang , Li Jiacheng , Zhu Yingying , Chen Chong , Liu Jing , Gu Simin , Zheng Yiyuan , Li Yong
Published: October 2023

Background

Epidemiological studies have indicated a potential link between the gut microbiome and autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The relationship between the gut microbiome and autoimmune liver disease is still uncertain due to confounding variables. In our study, we aim to shed light on this relationship by employing a two-sample Mendelian randomization approach.

Methods

We conducted a two-sample Mendelian randomization (MR) study using the R package "TwoSampleMR". The exposure data consisted of genetic variants associated with 194 bacterial traits obtained from the MiBioGen consortium. Summary statistics for AILD were obtained from the GWAS Catalog website. Furthermore, a series of sensitivity analyses were performed to validate the initial MR results.

Results

There were two, four and three bacteria traits associated with an increased risk of AIH. PBC, and PSC respectively. In contrast, there were five, two and five bacteria traits associated with a decreased risk for AIH, PBC and PSC. Notably, the genus_Clostridium_innocuum_group showed a negative association with AIH (OR = 0.67, 95% CI: 0.49–0.93), and the genus_Actinomyces was found to be genetically associated with a decreased risk of PSC (OR = 0.62, 95% CI: 0.42–0.90).

Conclusions

Our study identified the causal impact of specific bacterial features on the risk of AILD subtypes. Particularly, the genus_Clostridium_innocuum_group and the genus_Actinomyces demonstrated significant protective effects against AIH and PSC respectively. These findings provide further support for the potential use of targeted probiotics in the management of AILD.
HK3 stimulates immune cell infiltration to promote glioma deterioration
Authors: Li Shupeng , Li Ziwei , Wang Xinyu , Zhong Junzhe , Yu Daohan , Chen Hao , Ma Wenbin , Liu Lingling , Ye Minghuang , Shen Ruofei , Jiang Chuanlu , Meng Xiangqi , Cai Jinquan
Published: October 2023

Background

Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions between neoplastic cells and the surrounding microenvironment can generate an immunosuppressive TME, which can accelerate the malignant progression of glioma. Therefore, it is crucial to explore associations between energy metabolism and the immunosuppressive TME and to identify new biomarkers for glioma prognosis.

Methods

In our work, we analyzed the co-expression relationship between glycolytic genes and immune checkpoints based on the transcriptomic data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) and found the correlation between HK3 expression and glioma tumor immune status. To investigate the biological role of HK3 in glioma, we performed bioinformatics analysis and established a mouse glioblastoma (GBM) xenograft model.

Results

Our study showed that HK3 significantly stimulated immune cell infiltration into the glioma TME. Tissue samples with higher HK3 expressive level showed increasing levels of immune cells infiltration, including M2 macrophages, neutrophils, and various subtypes of activated memory CD4+ T cells. Furthermore, HK3 expression was significantly increasing along with the elevated tumor grade, had a higher level in the mesenchymal subtype compared with those in other subtypes of GBM and could independently predict poor outcomes of GBM patients.

Conclusion

The present work mainly concentrated on the biological role of HK3 in glioma and offered a novel insight of HK3 regulating the activation of immune cells in the glioma microenvironment. These findings could provide a new theoretical evidence for understanding the metabolic molecular within the glioma microenvironment and identifying new therapeutic targets.
Profiling small RNAs in fecal immunochemical tests: is it possible?
Authors: Birkeland Einar , Ferrero Giulio , Pardini Barbara , Umu Sinan U. , Tarallo Sonia , Bulfamante Sara , Hoff Geir , Senore Carlo , Rounge Trine B , Naccarati Alessio
Published: October 2023

Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.
The gut microbiome tango in the progression of chronic kidney disease and potential therapeutic strategies
Authors: Tang Zijing , Yu Shiyan , Pan Yu
Published: October 2023

Chronic kidney disease (CKD) affects more than 10% population worldwide and becomes a huge burden to the world. Recent studies have revealed multifold interactions between CKD and gut microbiome and their pathophysiological implications. The gut microbiome disturbed by CKD results in the imbalanced composition and quantity of gut microbiota and subsequent changes in its metabolites and functions. Studies have shown that both the dysbiotic gut microbiota and its metabolites have negative impacts on the immune system and aggravate diseases in different ways. Herein, we give an overview of the currently known mechanisms of CKD progression and the alterations of the immune system. Particularly, we summarize the effects of uremic toxins on the immune system and review the roles of gut microbiota in promoting the development of different kidney diseases. Finally, we discuss the current sequencing technologies and novel therapies targeting the gut microbiome.
Drivers, barriers, and response to care of Australian pregnant women seeking chiropractic care for low back and pelvic girdle pain: a qualitative case study
Authors: Bernard-Giglio Maria , French Simon D , Myburgh Corrie , de Luca Katie
Published: October 2023

Background

Pregnancy-related low back and/or pelvic girdle pain is common, with a prevalence rate of up to 86% in pregnant women. Although 19.5% of Australian pregnant women visit a chiropractor for pelvic girdle pain, little is known about the experience of pregnant women who seek this care. The aim of this study was to describe and explore the experiences of Australian pregnant women who seek chiropractic care for their current pregnancy-related low back and/or pelvic girdle pain.

Methods

A qualitative case study approach with purposive sampling from 27 chiropractic practices was used. A grounded theory approach was informed by a constructivist and interpretivist stance, which provided understanding and meaning to the pregnant women’s experiences. Online unstructured interviews were recorded, transcribed, and anonymised. A thematic analysis was subsequently conducted on the primary data. Codes and major themes were developed with the use of critical self- reflection (memos), survey finding triangulation and respondent validation.

Results

Sixteen potential respondents expressed interest in participating. After eligibility screening and data saturation, nine interviews were undertaken. Four key themes were identified: “Care drivers: what drives care seeking?”, “Care barriers: what barriers are encountered?”, “Chiropractic treatment: what does treatment consist of?” and “Response to care: what response was there to care?”.

Conclusion

Four key themes: care drivers, care barriers, chiropractic treatment, and response to care support an emergent substantive-level theory in women’s care seeking experiences for pregnancy-related back pain and chiropractic care. This theory is that chiropractic care for pregnant women experiencing low back pain and pelvic girdle pain may improve pain and function, while reducing pregnancy-related biopsychosocial concerns. The findings may inform antenatal health providers and the chiropractic profession about pregnant women’s experience seeking chiropractic care as well as directing future research.
Overcoming distance: an exploration of current practices of government and charity-funded critical care transport and retrieval organizations
Authors: Greene Adam , Dion Pierre-Marc , Nolan Brodie , Trachter Rob , Vu Erik , Trojanowski Jan
Published: October 2023

Background

For critically ill and injured patients, timely access to definitive care is associated with a reduction in avoidable mortality. Access to definitive care is significantly affected by geographic remoteness. To overcome this disparity, a robust critical care transport (CCT) or retrieval system is essential to support the equity of care and overcome the tyranny of distance. While critical care transport or retrieval systems have evolved over the years, there is no universally accepted system or standard, which has led to considerable variation in practices. The objective of this mixed-methods study was to identify and explore the current clinical, operational, and educational practices of government and charity-funded critical care transport and retrieval organizations operating across access- and weather- challenged geography.

Methods

This study utilized a mixed-methods approach comprising a rapid review of the literature and semi-structured interviews with identified subject matter experts (SME).

Results

A total of 44 articles and 14 interviews with SMEs from six different countries, 12 different services/systems, and seven operational roles, including clinicians (physician, paramedic, and nurse), educator, quality improvement, clinical governance, clinical informatics and research, operations manager, and medical director were included in the narrative analysis. The study identified several themes including deployment, crew composition, selection and education, clinical governance, quality assurance and quality improvement and research.

Conclusion

This mixed-methods study underscores the paucity of literature describing current clinical, operational, and educational practices of government or charity-funded CCT or retrieval programs operating across access- and weather- challenged geography. While many common themes were identified including clearly defined mission profiles, use of dedicated or specialized transport teams, central coordination, rigorous selection processes, service-sponsored graduate education, and strong clinical governance, there is little consensus and considerable variation in current practices. Further research is needed to identify and harmonize best practices within the CCT and retrieval environments.
Escherichia coli displays a conserved membrane proteomic response to a range of alcohols
Authors: Sen Oishi , Hinks Jamie , Lin Qifeng , Lin Qingsong , Kjelleberg Staffan , Rice Scott A. , Seviour Thomas
Published: October 2023

Background

Alcohol is a good and environment-friendly fuel that can be microbially produced, capable of eliminating many of the limitations of the present-day fossil fuels. However, the inherent toxic nature of alcohols to the microbial cells leads to end-product inhibition that limits large-scale alcohol production by fermentation. Fundamental knowledge about the stress responses of microorganisms to alcohols would greatly facilitate to improve the microbial alcohol tolerance. The current study elucidates and compares the changes in the membrane proteome of Escherichia coli in response to a range of alcohols.

Results

Although alcohol toxicity increased exponentially with alcohol chain length (2–6 carbon), similar stress responses were observed in the inner and outer membrane proteome of E. coli in the presence of 2-, 4- and 6-carbon alcohols at the MIC50. This pertains to: (1) increased levels of inner membrane transporters for uptake of energy-producing metabolites, (2) reduced levels of non-essential proteins, associated with anaerobic, carbon starvation and osmotic stress, for energy conservation, (3) increased levels of murein degrading enzymes (MltA, EmtA, MliC and DigH) promoting cell elongation and 4) reduced levels of most outer membrane β-barrel proteins (LptD, FadL, LamB, TolC and BamA). Major outer membrane β-barrel protein OmpC, which is known to contribute to ethanol tolerance and membrane integrity, was notably reduced by alcohol stress. While LPS is important for OmpC trimerisation, LPS release by EDTA did not lower OmpC levels. This suggests that LPS release, which is reported under alcohol stress, does not contribute to the reduced levels of OmpC in the presence of alcohol.

Conclusions

Since alcohol primarily targets the integrity of the membrane, maintenance of outer membrane OmpC levels in the presence of alcohol might help in the survival of E. coli to higher alcohol concentrations. The study provides important information about the membrane protein responses of E. coli to a range of alcohols, which can be used to develop targeted strategies for increased microbial alcohol tolerance and hence bioalcohol production.
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

Background

As 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.

Methods

This 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.

Results

The 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.

Conclusion

This 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

Mycobacterium 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

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

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

Respiratory 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

Aspergillus 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

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

Introducing 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

Many 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

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.