bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex clinical manifestations and new insights in RNA sequencing of children with diabetes and WFS1 variants
Authors: Ding Yu , Li Zhe , Zhang Qianwen , Li Niu , Chang Guoying , Wang Yirou , Li Xin , Li Juan , Li Qun , Yao Ru-en , Li Xin , Wang Xiumin 
Published: March 2023

BackgroundWFS1-related disorders involve a wide range of clinical phenotypes, including diabetes mellitus and neurodegeneration. Inheritance patterns of pathogenic variants of this gene can be autosomal recessive or dominant, and differences in penetrance present challenges for accurate diagnosis and genetic counselling.MethodsThree probands and one elder brother from three families were systematically evaluated and the clinical data of other family members were collected from the medical history. Whole-exome sequencing was performed on the probands, and RNA sequencing was performed on four patients, their parents with WFS1 variants, and four gender- and age-matched children with type 1 diabetes mellitus.ResultsThere were six patients with diabetes. Dilated cardiomyopathy, a rare manifestation of WFS1-related disease, was identified in one patient, along with MRI findings of brain atrophy at age 7 years and 3 months, the earliest age of discovery we know of. Whole-exome sequencing revealed five pathogenic or likely pathogenic variants in the WFS1 gene, including c.1348dupC (p.His450Profs*93), c.1381A&gt;C (p.Thr461pro), c.1329C&gt;G (p.Ser443Arg), c.2081delA (p.Glu694Glyfs*16), c.1350-1356delinsGCA (p.His450Glnfs*26), of which 3 variants (c.1348dupC, c.2081delA, c.1350-1356delinsGCA) were novel that have not been previously reported. The differentially expressed genes were mainly associated with immune-related pathways according to the Gene Ontology enrichment analysis of the RNA sequencing data. The exon 1 region of HLA-DRB1 in two patients was not transcribed, while the transcription of the region in their parents was normal.ConclusionThis study emphasizes the clinical and genetic heterogeneity in patients, even in the same family with WFS1 variants. MRI evaluation of the brain should be considered when WFS1-related disorder is first diagnosed.
Identification of diagnostic markers related to oxidative stress and inflammatory response in diabetic kidney disease by machine learning algorithms: Evidence from human transcriptomic data and mouse experiments
Authors: Zhong Ming , Zhu Enyi , Li Na , Gong Lian , Xu Hai , Zhong Yong , Gong Kai , Jiang Shan , Wang Xiaohua , Fei Lingyan , Tang Chun , Lei Yan , Wang Zhongli , Zheng Zhihua 
Published: March 2023

IntroductionDiabetic kidney disease (DKD) is a long-term complication of diabetes and causes renal microvascular disease. It is also one of the main causes of end-stage renal disease (ESRD), which has a complex pathophysiological process. Timely prevention and treatment are of great significance for delaying DKD. This study aimed to use bioinformatics analysis to find key diagnostic markers that could be possible therapeutic targets for DKD.MethodsWe downloaded DKD datasets from the Gene Expression Omnibus (GEO) database. Overexpression enrichment analysis (ORA) was used to explore the underlying biological processes in DKD. Algorithms such as WGCNA, LASSO, RF, and SVM_RFE were used to screen DKD diagnostic markers. The reliability and practicability of the the diagnostic model were evaluated by the calibration curve, ROC curve, and DCA curve. GSEA analysis and correlation analysis were used to explore the biological processes and significance of candidate markers. Finally, we constructed a mouse model of DKD and diabetes mellitus (DM), and we further verified the reliability of the markers through experiments such as PCR, immunohistochemistry, renal pathological staining, and ELISA.ResultsBiological processes, such as immune activation, T-cell activation, and cell adhesion were found to be enriched in DKD. Based on differentially expressed oxidative stress and inflammatory response-related genes (DEOIGs), we divided DKD patients into C1 and C2 subtypes. Four potential diagnostic markers for DKD, including tenascin C, peroxidasin, tissue inhibitor metalloproteinases 1, and tropomyosin (TNC, PXDN, TIMP1, and TPM1, respectively) were identified using multiple bioinformatics analyses. Further enrichment analysis found that four diagnostic markers were closely related to various immune cells and played an important role in the immune microenvironment of DKD. In addition, the results of the mouse experiment were consistent with the bioinformatics analysis, further confirming the reliability of the four markers.ConclusionIn conclusion, we identified four reliable and potential diagnostic markers through a comprehensive and systematic bioinformatics analysis and experimental validation, which could serve as potential therapeutic targets for DKD. We performed a preliminary examination of the biological processes involved in DKD pathogenesis and provide a novel idea for DKD diagnosis and treatment.
Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders
Authors: Akter Hosneara , Rahman Muhammad Mizanur , Sarker Shaoli , Basiruzzaman Mohammed , Islam Md. Mazharul , Rahaman Md. Atikur , Rahaman Md. Ashiquir , Eshaque Tamannyat Binte , Dity Nushrat Jahan , Sarker Shouvik , Amin Md. Robed , Hossain Mohammad Monir , Lopa Maksuda , Jahan Nargis , Hossain Shafaat , Islam Amirul , Mondol Ashaduzzaman , Faruk Md Omar , Saha Narayan , Kundu Gopen kumar , Kanta Shayla Imam , Kazal Rezaul Karim , Fatema Kanij , Rahman Md. Ashrafur , Hasan Maruf , Hossain Mollah Md. Abid , Hosen Md. Ismail , Karuvantevida Noushad , Begum Ghausia , Zehra Binte , Nassir Nasna , Nabi A. H. M. Nurun , Uddin K. M. Furkan , Uddin Mohammed 
Published: March 2023

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh.Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., “Critical-Exon Genes (CEGs)”] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package.Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients’ pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (&lt;1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability.Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.
Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs
Authors: Guilherme Rafael F. , Silva José Bruno N.F. , Waclawiack Ingrid , Fraga-Junior Vanderlei S. , Nogueira Thaís O. , Pecli Cyntia , Araújo-Silva Carlla A. , Magalhães Nathalia S. , Lemos Felipe S. , Bulant Carlos A. , Blanco Pablo J. , Serra Rafaela , Svensjö Erik , Scharfstein Júlio , Moraes João A. , Canetti Claudio , Benjamim Claudia F. 
Published: March 2023

IntroductionPulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments.MethodsUsing a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later.Results and discussionAssessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-β, and TGF-β. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-β-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-β-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.
Age-adjusted Charlson comorbidity index predicts postoperative mortality in elderly patients with hip fracture: A prospective cohort
Authors: Zhang Dan-Long , Cong Yu-Xuan , Zhuang Yan , Xu Xin , Zhang Bin-Fei 
Published: March 2023

BackgroundThis study aimed to evaluate the clinical association between the age-adjusted Charlson comorbidity index (aCCI) and postoperative mortality in elderly patients.Materials and methodsElderly patients with hip fractures were screened from January 2015 to September 2019. After demographic and clinical characteristics were collected, linear and non-linear multivariate Cox regression models were used to identify the association between the aCCI and mortality. All analyses were performed using EmpowerStats and R software.ResultsA total of 2,657 patients were included in the study, and the mean follow-up duration was of 38.97 months. The mean aCCI score was 4.24 ± 1.09, and 977 (34.14%) died of all-cause mortality. The fully-adjusted linear multivariate Cox regression models showed the aCCI to be associated with mortality [hazard ratio (HR) = 1.31, 95% confidence interval (CI):1.21–1.41, P &lt; 0.0001]. Patients in Q2 showed greater mortality (HR = 1.60, 95% CI: 1.23–2.09; P = 0.0005) than those in Q1; patients in Q3 showed greater mortality (HR = 2.18, 95% CI: 1.66–2.87; P &lt; 0.001) than those in Q1. In addition, the P-value for the trend also showed a linear association in the three models (P &lt; 0.0001). In the sensitivity analysis, propensity score matching was used, and the results were stable.ConclusionThe mortality risk of hip fractures increased by 31% when the aCCI increased by one unit. aCCI score was shown to be a good predictor of three-year mortality following hip fracture.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=152919, identifier ChiCTR2200057323.
Effectiveness of small-angle episiotomy on incisional laceration rate, suturing time, and incisional bleeding in primigravida: A meta-analysis
Authors: Zhang Yan , Zhang Jiaoyan , Zhao Liang , Xiao Lin , Tian Jinhui , Fan Wei 
Published: March 2023

ObjectiveTo investigate the effect of small-angle lateral perineal incision on postoperative perineal rehabilitation in primiparous women.MethodThe Cochrane Library, PubMed, Embase, CINAHL, CNKI, WanFang, VIP, and the Chinese Biomedical Literature Database were searched for randomized controlled trials (RCTs) on the effect of small-angle episiotomy on postoperative maternal perineal wound rehabilitation in puerpera until April 3, 2022. Two researchers independently performed literature screening, data extraction and evaluation of risk of bias in the included literature, and statistical analysis of the data was performed using RevMan 5.4 and Stata 12.0 software.ResultA total of 25 RCTs were included, with a total sample of 6,366 cases. Meta-analysis results showed that the use of small-angle episiotomy reduced incisional tearing [OR = 0.32, 95% CI (0.26, 0.39)], shortened incisional suture time [MD = −4.58 min, 95% CI (−6.02, −3.14)] and reduced incisional bleeding [MD = −19.08 mL, 95% CI (−19.53, −18.63)], with statistically significant differences (all p &lt; 0.05). There was no significant difference in the rate of severe laceration between the two groups [OR = 2.32, 95% CI (0.70, 7.70), p &gt; 0.05].ConclusionThe use of a small-angle episiotomy during vaginal delivery can reduce the incision tear rate without increasing the incidence of severe perineal laceration, while shortening the incisional suturing time and reducing incisional bleeding. It can be used clinically according to birth canal conditions of the maternal, the intrauterine condition of the fetus and maternal needs.Systematic Review RegistrationPROSPERO International Prospective Register of Systematic Reviews [CRD42022369698]; [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369698].
Synergistic antifungal interaction of N-(butylcarbamothioyl) benzamide and amphotericin B against Cryptococcus neoformans
Authors: Andriani Gabriella Maria , Spoladori Lais Fernanda de Almeida , Fabris Marciéli , Camargo Priscila Goes , Pereira Patrícia Morais Lopes , Santos Jussevania Pereira , Bartolomeu-Gonçalves Guilherme , Alonso Lais , Lancheros Cesar Armando Contreras , Alonso Antonio , Nakamura Celso Vataru , Macedo Fernando , Pinge-Filho Phileno , Yamauchi Lucy Megumi , Bispo Marcelle de Lima Ferreira , Tavares Eliandro Reis , Yamada-Ogatta Sueli Fumie 
Published: March 2023

IntroductionCryptococcus neoformans is one of the leading causes of invasive fungal infections worldwide. Cryptococcal meningoencephalitis is the main challenge of antifungal therapy due to high morbidity and mortality rates, especially in low- and middle-income countries. This can be partly attributed to the lack of specific diagnosis difficulty accessing treatment, antifungal resistance and antifungal toxicity.MethodsIn the present study, the effect of the synthetic thiourea derivative N-(butylcarbamothioyl) benzamide (BTU-01), alone and combined with amphotericin B (AmB), was evaluated in planktonic and sessile (biofilm) cells of C. neoformans.ResultsBTU-01 alone exhibited a fungistatic activity with minimal inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL for planktonic cells; and sessile MICs ranging from 125.0 to 1000.0 μg/mL. BTU-01 caused a concentration-dependent inhibitory activity on cryptococcal urease and did not interfere with plasma membrane fluidity. Molecular docking was performed on Canavalia ensiformis urease, and BTU-01 showed relevant interactions with the enzyme. The combination of BTU-01 and AmB exhibited synergistic fungicidal activity against planktonic and sessile cells of C. neoformans. Microscopic analysis of C. neoformans treated with BTU-01, alone or combined with AmB, revealed a reduction in cell and capsule sizes, changes in the morphology of planktonic cells; a significant decrease in the number of cells within the biofilm; and absence of exopolymeric matrix surrounding the sessile cells. Neither hemolytic activity nor cytotoxicity to mammalian cells was detected for BTU-01, alone or combined with AmB, at concentrations that exhibited antifungal activity. BTU-01 also displayed drug-likeness properties.ConclusionThese results indicate the potential of BTU-01, for the development of new strategies for controlling C. neoformans infections.
Effects of rice blast biocontrol strain Pseudomonas alcaliphila Ej2 on the endophytic microbiome and proteome of rice under salt stress
Authors: Zeng Qingchao , Man Xiaowu , Huang Zeyang , Zhuang Lubo , Yang Hanmeng , Sha Yuexia 
Published: March 2023

IntroductionSoil salinity is a prevalent environmental stress in agricultural production. Microbial inoculants could effectively help plants to alleviate salt stress. However, there is little knowledge of the biocontrol strain Pseudomonas alcaliphila Ej2 mechanisms aiding rice plants to reduce the adverse effects caused by salt stress.MethodsWe performed integrated field and greenhouse experiments, microbial community profiling, and rice proteomic analysis to systematically investigate the Ej2 mechanism of action.ResultsThe results displayed that biocontrol strain Ej2 increased shoot/root length and fresh/dry weight compared with control under salt stress. Meanwhile, strain Ej2 has the ability to control rice blast disease and promote rice growth. Furthermore, the microbial community analysis revealed that the alpha-diversity of Ej2-inoculated plants was higher than the control plants, expect the Shannon index of the bacterial microbiome and the Ej2-inoculated samples clustered and separated from the control samples based on beta-diversity analysis. Importantly, the enriched and specific OTUs after Ej2 inoculation at the genus level were Streptomyces, Pseudomonas, Flavobacterium, and Bacillus. Moreover, we observed that Ej2 inoculation influenced the rice proteomic profile, including metabolism, plant-pathogen interactions, and biosynthesis of unsaturated fatty acids. These results provide comprehensive evidence that Ej2 inoculation induced the rice endophytic microbiome and proteomic profiles to promote plant growth under salt stress.DiscussionUnderstanding the biocontrol strain effects on the endophytic microbiome and rice proteomics will help us better understand the complex interactions between plants and microorganisms under salt stress. Furthermore, unraveling the mechanisms underlying salt tolerance will help us more efficiently ameliorate saline soils.
DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
Authors: Hu Wei , Li Ping , Zeng Nianju , Tan Sheng 
Published: March 2023

ObjectiveIschemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and adjusting treatment strategies because neurological assessment after stroke treatment is mostly performed using scales and imaging. Therefore, there is an urgent need to find biomarkers that can help us evaluate and optimize the treatment plan.MethodsWe used data-independent acquisition (DIA) technology to screen differentially expressed proteins (DEPs) before and after ischemic stroke rehabilitation treatment, and then performed Gene Ontology (GO) and pathway enrichment analysis of DEPs using bioinformatics tools such as KEGG pathway and Reactome. In addition, the protein–protein interaction (PPI) network and modularity analysis of DEPs were integrated to identify the hub proteins (genes) and hub signaling pathways for neurological recovery in ischemic stroke. PRM-targeted proteomics was also used to validate some of the screened proteins of interest.ResultsAnalyzing the serum protein expression profiles before and after rehabilitation, we identified 22 DEPs that were upregulated and downregulated each. Through GO and pathway enrichment analysis and subsequent PPI network analysis constructed using STRING data and subsequent Cytoscape MCODE analysis, we identified that complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammatory and immune pathways are the major pathways involved in the improvement of neurological function after stroke rehabilitation.ConclusionComplement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammation and immunity pathways are not only key pathways in the pathogenesis of ischemic stroke but also the main pathways of action of rehabilitation therapy. In addition, IGHA1, LRG1, IGHV3-64D, and CP are upregulated in patients with ischemic stroke and downregulated after rehabilitation, which may be used as biomarkers to monitor neurological impairment and recovery after stroke.