bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of resistance genes and plasmids from sick children caused by Salmonella enterica resistance to azithromycin in Shenzhen, China
Authors: Wang Hongmei , Cheng Hang , Huang Baoxing , Hu Xiumei , Chen Yunsheng , Zheng Lei , Yang Liang , Deng Jikui , Wang Qian 
Published: March 2023

IntroductionSamonella is 1 of 4 key global causes of diarrhoeal diseases, sometimes it can be serious, especially for yong children. Due to the extensive resistance of salmonella serotypes to conventional first-line drugs, macrolides (such as azithromycin) have been designated as the most important antibiotics for the treatment of salmonella. Antimicrobial resistance is a major public health problem in the world, and the mechanism of azithromycin resistance is rarely studied.MethodsThis study determined the azithromycin resistance and plasmids of Salmonella enterica isolates from children attending the Shenzhen Children’s Hospital. The susceptibility of ampicillin (AMP), ciprofloxacin (CIP), ceftriaxone (CRO), sulfamethoxazole (SMZ), chloramphenicol (CL), and azithromycin (AZM) were detected and the genes and plasmids from azithromycin-resistant Salmonella were detected by Illumina hi-seq and Nanopore MinIone whole genome sequencing (WGS) using a map-based method, and the genomic background of these factors was evaluated using various bioinformatics tools.ResultsIn total, 15 strains of nontyphoid Salmonella strains that were isolated (including S. typhimurium, S.London, S. Goldcoast, and S.Stanley) demonstrated resistance to azithromycin (minimum inhibitory concentration,MIC from 32 to &gt;256 µg/mL), and the resistance rate was 3.08% (15/487). The sensitivity test to other antibiotics demonstrated 100% resistance to AMP, and the resistance to SMZ and CL was 86.7% and 80.0%, respectively. Through WGS analysis, all isolates were positive for a plasmid-encoded mphA gene. Plasmid incompatibility typing identified five IncFIB(K), five IncHI2/HI2A/Q1, two IncC, one IncHI2/HI2A/N, one IncR, one IncFII and one IncHI2/HI2A plasmids. Sequence analyses of plasmids revealed extensive homology to various plasmids or transposons in regions involved in plasmid replication/maintenance functions and/or in antibiotic resistance gene clusters.ConclusionmphA is the main gene involved in azithromycin, a macrolide, and resistance to Salmonella. It is usually located on plasmids and easily spreads, hence posing a great threat to the current treatment of Salmonella infection. The plasmid sequence similarities suggest that the plasmids acquired resistance genes from a variety of enterica bacteria and underscore the importance of a further understanding of horizontal gene transfer among enterica bacteria.
Effects of recreational SCUBA diving practiced once a week on neurohormonal response and myokines-mediated communication between muscles and the brain
Authors: Njire Braticevic Marina , Zarak Marko , Simac Brankica , Perovic Antonija , Dumic Jerka 
Published: March 2023

ObjectiveDuring physical activity, activation of muscular, endocrine, and nervous systems, results in intensive crosstalk between muscles and other organs, which enables response to physiological stress. In SCUBA diving, extreme environmental conditions represent an additional challenge for homeostasis maintenance, but underlying mechanisms are largely unknown. We aimed to contribute to the understanding of neurohormonal response and muscle-brain crosstalk by measuring the concentrations of the selected hormones secreted by the pituitary-target organ axis and myokines involved in the muscle-brain endocrine loop in recreational SCUBA (rSCUBA) divers.MethodsFourteen male divers performed five open-water recreational dives (one per week, depth of 20–30 m, lasting 30 min, between 9 and 10 am), after a winter non-diving period of 5 months. Blood samples were collected immediately before and after the first, third, and fifth dives. Adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free thyroxine (fT4), prolactin, total testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), irisin, brain-derived neurotrophic factor (BDNF), S100B, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) were measured using commercially available immunoassays.ResultsCortisol and ACTH levels decreased after every dive, while total testosterone decreased only after the first dive. No significant changes in post-dive values, as well as the cumulative effect on any other measured hormone, were observed. Although irisin and BDNF levels decreased after the first and third dives, the fifth dive caused a significant increase in both myokines. Changes in IGF-1 levels were not observed. All three dives caused a significant increase in S100B levels. A statistically significant decrease in GFAP concentration was observed after every dive, while NSE pre-dive concentration declined over the studied period. The cumulative effect on myokine levels was reflected in a continuous decline in irisin and BDNF pre-dive levels throughout the studied period, but an increasing trend after the fifth dive was observed.ConclusionsObserved changes in myokines and hormone levels point to a specific response to rSCUBA practiced once a week, most likely due to extreme environmental conditions. Further studies on communication between muscles and other organ systems, particularly on the muscle-brain endocrine loop, are required for a deeper understanding of the adaptation mechanisms to this kind of physiological stress.
Identification and validation of key genes associated with atrial fibrillation in the elderly
Authors: Liu Chuanbin , Zeng Jing , Wu Jin , Wang Jing , Wang Xin , Yao Minghui , Zhang Minghua , Fan Jiao 
Published: March 2023

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of stroke and heart failure (HF), contributing to a higher mortality rate. Increasing age is a major risk factor for AF; however, the mechanisms of how aging contributes to the occurrence and progression of AF remain unclear. This study conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes and determine their potential associations with aging-related AF.Materials and methodsWGCNA was performed using the AF dataset GSE2240 obtained from the Gene Expression Omnibus, which contained data from atrial myocardium in cardiac patients with permanent AF or sinus rhythm (SR). Hub genes were identified in clinical samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed.ResultsGreen and pink were the most critical modules associated with AF, from which nine hub genes, PTGDS, COLQ, ASTN2, VASH1, RCAN1, AMIGO2, RBP1, MFAP4, and ALDH1A1, were hypothesized to play key roles in the AF pathophysiology in elderly and seven of them have high diagnostic value. Functional enrichment analysis demonstrated that the green module was associated with the calcium, cyclic adenosine monophosphate (cAMP), and peroxisome proliferator-activated receptors (PPAR) signaling pathways, and the pink module may be associated with the transforming growth factor beta (TGF-β) signaling pathway in myocardial fibrosis.ConclusionWe identified nine genes that may play crucial roles in the pathophysiological mechanism of aging-related AF, among which six genes were associated with AF for the first time. This study provided novel insights into the impact of aging on the occurrence and progression of AF, and identified biomarkers and potential therapeutic targets for AF.
Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs—A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial
Authors: Chen Wannhsin , Hou Chun-Hsiang , Chen Yi-Ling , Shen Hsin-Hsin , Lin Chen-Hsuan , Wu Cheng-Yi , Lin Meng-Hsueh , Liao Chih-Ching , Huang Jun-Jae , Yang Chi-Yu , Li Yi-Chen , Yip Hon-Kan 
Published: March 2023

BackgroundThis study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective.Methods and resultsYoung male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p &lt; 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p &lt; 0.001). The ST-segment resolution (&gt;80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p &lt; 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p &lt; 0.001).ConclusionEarly intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI.
Response to pioglitazone in non-alcoholic fatty liver disease patients with vs. without type 2 diabetes: A meta-analysis of randomized controlled trials
Authors: Wang Zeyu , Du Huiqing , Zhao Ying , Ren Yadi , Ma Cuihua , Chen Hongyu , Li Man , Tian Jiageng , Xue Caihong , Long Guangfeng , Xu Meidong , Jiang Yong 
Published: March 2023

BackgroundPioglitazone is considered a potential therapy for non-alcoholic fatty liver disease (NAFLD). However, different effects of pioglitazone on NAFLD have been demonstrated in diabetic and non-diabetic patients. Herein, a meta-analysis of randomized, placebo-controlled trials was carried out to indirectly compare pioglitazone in NAFLD patients with vs. without type 2 diabetes.MethodsRandomized controlled trials (RCTs) of pioglitazone vs. placebo involving NAFLD patients with or without type 2 diabetes/prediabetes collected from databases were enrolled into this analysis. Methodological quality was employed to evaluate the domains recommended by the Cochrane Collaboration. The analysis covered the changes in histology (fibrosis, hepatocellular ballooning, inflammation, steatosis), liver enzymes, blood lipids, fasting blood glucose (FBS), homeostasis model assessment-IR (HOMA-IR), weight and body mass index (BMI) before and after treatment, and adverse events.ResultsThe review covered seven articles, with 614 patients in total, of which three were non-diabetic RCTs. No difference was found in patients with vs. without type 2 diabetes in histology, liver enzymes, blood lipids, HOMA-IR, weight, BMI, and FBS. Moreover, no significant difference was revealed in adverse effects between NAFLD patients with diabetes and without DM, except the incidence of edema that was found to be higher in the pioglitazone group than in the placebo group in NAFLD patients with diabetes.ConclusionsPioglitazone could exert a certain effect on alleviating NAFLD, which was consistent between non-diabetic NAFLD patients and diabetic NAFLD patients in improving histopathology, liver enzymes, and HOMA-IR and reducing blood lipids. Furthermore, there were no adverse effects, except the incidence of edema which is higher in the pioglitazone group in NAFLD patients with diabetes. However, large sample sizes and well-designed RCTs are required to further confirm these conclusions.
The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors
Authors: Kober Paulina , Rusetska Natalia , Mossakowska Beata J. , Maksymowicz Maria , Pękul Monika , Zieliński Grzegorz , Styk Andrzej , Kunicki Jacek , Działach Łukasz , Witek Przemysław , Bujko Mateusz 
Published: March 2023

ObjectivePituitary neuroendocrine corticotroph tumors commonly cause Cushing’s disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic–pituitary–adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs via glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors.MethodsNinety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of NR3C1 and NR3C2 coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry.ResultsBoth GR and MR were expressed in corticotroph tumors. Correlation between NR3C1 and NR3C2 expression levels was observed. NR3C1 expression was higher in silent than in functioning tumors. In CD patients NR3C1 and NR3C2 levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher NR3C2 was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in USP8-mutated tumors. Similar relationship between USP8 mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher NR3C1 expression in densely granulated tumors.ConclusionsAlthough the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.
Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women
Authors: Li Na , Xu Wanxue , Liu Huimin , Zhou Rui , Zou Siqi , Wang Shiqing , Li Siyu , Yang Zexin , Piao Yongjun , Zhang Yunshan 
Published: March 2023

Background: Diminished ovarian reserve is one of the most important causes of female infertility. In the etiology study of DOR, besides age, it is known that chromosomal abnormality, radiotherapy, chemotherapy and ovarian surgery can result in DOR. For young women without obvious risk factors, gene mutation should be considered as a possible cause. However, the specific molecular mechanism of DOR has not been fully elucidated.Methods: In order to explore the pathogenic variants related to DOR, twenty young women under 35 years old affected by DOR without definite factors damaging ovarian reserve were recruited as the research subjects, and five women with normal ovarian reserve were recruited as the control group. Whole exome sequencing was applied as the genomics research tool.Results: As a result, we obtained a set of mutated genes that may be related to DOR, where the missense variant on GPR84 was selected for further study. It is found that GPR84Y370H variant promotes the expression of proinflammatory cytokines (TNF-α, IL12B, IL-1β) and chemokines (CCL2, CCL5), as well as the activation of NF-κB signaling pathway.Conclusion: In conclusion, GPR84Y370H variant was identified though analysis for WES results of 20 DOR patients. The deleterious variant of GPR84 could be the potential molecular mechanism of non-age-related pathological DOR through its role in promoting inflammation. The findings of this study can be used as a preliminary research basis for the development of early molecular diagnosis and treatment target selection of DOR.
Impact of COVID-19 stress on the psychological health of sexual & gender minority individuals: A systematic review
Authors: Datta Sumona , Mukherjee Tilottama 
Published: March 2023

IntroductionThe differential effect of the Covid-19 pandemic on the mental health of the population around the globe is well documented. Social isolation, loss of job, financial crisis, and fear of infection due to the pandemic have widely affected people across countries, and the sexual and gender minority (SGM) group is no exception. However, the additional stressors like stigma, discrimination, rejection, non-acceptance, and violence associated with diverse sexual orientation complicated the situation for the SGM group in the context of the Covid-19 pandemic.MethodThe present study conducted a systematic review of research (n = 16) investigating the impact of Covid-19 stress on the psychological health of SGM individuals. The review had two objectives: (a) to explore the effect of the stress associated with the pandemic on the psychological health of the SGM individuals; and (b) to identify potential stressors associated with the Covid-19 pandemic affecting the mental health of SGM individuals. Studies were selected following a PRISMA protocol and several inclusion criteria.ResultsThe review provided new insights into the mental health issues of the SGM individual in the Covid-19 context. The outcome of the review focused on five aspects: (a) depression and anxiety symptoms related to Covid-19 symptoms; (b) perceived social support and Covid-19 stress; (c) family support and psychological distress related to Covid-19; (d) Covid-19 stress and disordered eating, and (e) problem drinking and substance abuse associated with Covid-19 stress.DiscussionThe present review indicated a negative association between Covid-19 stress and psychological distress among sexual and gender minority individuals. The findings have important implications for psychologists and social workers working with this population and policymakers around the globe.
HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development
Authors: Elnaggar Jacob H. , Huynh Victoria O. , Lin Daniel , Hillman R. Tyler , Abana Chike O. , El Alam Molly B. , Tomasic Katarina C. , Karpinets Tatiana V. , Kouzy Ramez , Phan Jae L. , Wargo Jennifer , Holliday Emma B. , Das Prajnan , Mezzari Melissa P. , Ajami Nadim J. , Lynn Erica J. , Minsky Bruce D. , Morris Van K. , Milbourne Andrea , Messick Craig A. , Klopp Ann H. , Futreal P. Andrew , Taniguchi Cullen M. , Schmeler Kathleen M. , Colbert Lauren E. 
Published: March 2023

BackgroundSquamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.MethodsPatients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.Results60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal.ConclusionAlthough alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.
Identification and validation of hub genes in drug induced acute kidney injury basing on integrated transcriptomic analysis
Authors: Deng Yi-Xuan , Liu Kun , Qiu Qun-Xiang , Tang Zhi-Yao , Que Rui-Man , Li Dian-Ke , Gu Xu-Rui , Zhou Guang-Liang , Wu Yi-Feng , Zhou Ling-Yun , Yin Wen-Jun , Zuo Xiao-Cong 
Published: March 2023

BackgroundDrug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers.MethodsDifferentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin’s were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models’ hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene’s potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples.Results95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence &gt;0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI.ConclusionThe immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.