bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrahepatic infiltration of activated CD8+ T cells and mononuclear phagocyte is associated with idiosyncratic drug-induced liver injury
Authors: Yang Hyun , Han Ji Won , Lee Jae Jun , Lee Ahlim , Cho Sung Woo , Rho Pu Reun , Kang Min-Woo , Jang Jeong Won , Jung Eun Sun , Choi Jong Young , Sung Pil Soo , Bae Si Hyun 
Published: March 2023

BackgroundIdiosyncratic drug-induced liver injury (DILI) is caused by the interplay among drugs, their metabolites, and the host immune response. The characterization of infiltrated immune cells in the liver may improve the understanding of the pathogenesis of idiosyncratic DILI. This study investigated the phenotypes and clinical implications of liver-infiltrating immune cells in idiosyncratic DILI.MethodsFrom January 2017 to June 2021, 53 patients with idiosyncratic DILI who underwent liver biopsy were prospectively enrolled in this study. Immunohistochemical staining and flow cytometry analyses were performed on the biopsy specimens. Serum levels of CXC chemokine ligand 10 (CXCL10) and soluble CD163 were measured. A multivariate cox proportional hazards model was used to evaluate predictors of DILI resolution within 30 days.ResultsThe numbers of intrahepatic T cells and mononuclear phagocytes were positively correlated with serum levels of total bilirubin, alanine aminotransferase (ALT), and the model of end-stage liver disease score. The frequency of activated CD8+ T cells among liver-infiltrating CD8+ T cells in DILI livers was higher than that in healthy livers. Notably, the percentages of activated intrahepatic CD8+ T cells and mononuclear phagocytes in DILI livers showed a positive correlation with ALT. Additionally, serum CXCL10 level was positively correlated with intrahepatic T cell infiltration and ALT, and soluble CD163 level was positively correlated with intrahepatic mononuclear phagocyte infiltration and ALT. Thirty-six patients (70.6%) were treated with steroids. In multivariate analysis, total bilirubin and steroid use independently influenced DILI resolution within 30 days.ConclusionsActivated CD8+ T cells and mononuclear phagocyte are associated with liver injury caused by drugs. Therefore, we suggest that steroids are a potential treatment option for idiosyncratic DILI.
Evaluation of the specificity of an intradermal test with recombinant tuberculosis allergen in Bacillus Calmette–Guérin-vaccinated healthy volunteers
Authors: Vasilyeva Irina A. , Aksenova Valentina A. , Kazakov Alexey V. , Kiseleva Yulia Y. , Maryandyshev Andrey O. , Dolzhenko Elena N. , Abramchenko Anna V. , Klevno Nadejda I. , Glebov Konstantin A. , Panova Anna E. , Petrova Larisa Y. , Sheikis Elena G. , Seregina Inna V. , Nikishova Elena I. , Doktorova Natalia P. , Samoilova Anastasia G. 
Published: March 2023

IntroductionThe tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test.Study objectiveTo assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis.MethodsA multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18–30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068).ResultsIn individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92–99%) with a cut-off of &gt;0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94–100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test.ConclusionDiaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.
The role of secure instant messaging applications in medical education: Evaluating student satisfaction in a case-based learning program using Siilo
Authors: Shahar Tali , Tadmor Offer , Dior Uri , Porat Shay , Safrai Myriam , Ezra Yosef , Kabiri Doron 
Published: March 2023

BackgroundInstant messaging applications for mobile phones have recently grown in popularity among medical personnel, including both physicians and medical students. During the COVID-19 pandemic, medical education was largely transferred to virtual platforms, making such applications an increasingly important tool for medical education. “Siilo” is a secure instant messaging application that was designed for medical professionals, and offers several advantages over other instant messaging services that are vital for its use in medical settings, including information security, data encryption, and a built-in blurring tool to maintain patient privacy. In addition, Siilo allows for the creation of individual folders for each case, enabling users to conduct separate discussions about multiple patients simultaneously.ObjectiveTo evaluate student satisfaction in a case-based learning program using Siilo as a medical education tool in improving student learning outcomes and motivation.MethodsA case-based learning program was conducted with 24 fifth-year medical students using Siilo to evaluate its effectiveness as a medical education tool. The program was evaluated through the use of pre- and post-program questionnaires and focus group discussions to assess student satisfaction.ResultsThe majority of students (83.3%) were highly satisfied with the Siilo platform and felt that it enhanced their learning experience, and a majority of students (79.1%) reported that the program was highly effective. Students reported that the platform was easy to use and provided a clear and organized way to follow discussions about cases. The focus group discussions further revealed that students appreciated the real-time communication and felt that the use of Siilo helped to improve the quality of communication and collaboration during the learning process. The use of Siilo as a medical education tool was found to contribute to positive relationships between doctors and students and improve student motivation for learning and outcomes.ConclusionThese findings suggest that Siilo can be a valuable resource for medical education, particularly due to its secure and convenient features, which are well-suited for use in medical settings. The use of Siilo in a case-based learning program was found to be effective in improving student satisfaction and learning outcomes and contributed to positive relationships between doctors and students. These results highlight the potential for utilizing mobile instant messaging apps as a tool for enhancing clinical teaching in medical education.
Microbiota alteration of Chinese young male adults with high-status negative cognitive processing bias
Authors: Xu Hui-Min , Xie Shen-Wei , Liu Tian-Yao , Zhou Xia , Feng Zheng-Zhi , He Xie 
Published: March 2023

IntroductionEvidence suggests that negative cognitive processing bias (NCPB) is a significant risk factor for depression. The microbiota–gut–brain axis has been proven to be a contributing factor to cognitive health and disease. However, the connection between microbiota and NCPB remains unknown. This study mainly sought to explore the key microbiota involved in NCPB and the possible pathways through which NCPB affects depressive symptoms.MethodsData in our studies were collected from 735 Chinese young adults through a cross-sectional survey. Fecal samples were collected from 35 young adults with different levels of NCPB (18 individuals were recruited as the high-status NCPB group, and another 17 individuals were matched as the low-status NCPB group) and 60 with different degrees of depressive symptoms (27 individuals were recruited into the depressive symptom group, as D group, and 33 individuals were matched into the control group, as C group) and analyzed by the 16S ribosomal RNA sequencing technique.ResultsAs a result, the level of NCPB correlated with the degree of depressive symptoms as well as anxiety symptoms and sleep quality (p &lt; 0.01). The β-diversity of microbiota in young adults was proven to be significantly different between the high-status NCPB and the low-status NCPB groups. There were several significantly increased bacteria taxa, including Dorea, Christensenellaceae, Christe -senellaceae_R_7_group, Ruminococcaceae_NK4A214_group, Eggerthellaceae, Family-XIII, Family_XIII_AD3011_group, Faecalibaculum, and Oscillibacter. They were mainly involved in pathways including short-chain fatty acid (SCFA) metabolism. Among these variable bacteria taxa, Faecalibaculum was found associated with both NCPB and depressive symptoms. Furthermore, five pathways turned out to be significantly altered in both the high-status NCPB group and the depressive symptom group, including butanoate metabolism, glyoxylate and dicarboxylate metabolism, propanoate metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, valine, leucine, and isoleucine degradation. These pathways were related to SCFA metabolism.DiscussionFecal microbiota is altered in Chinese young male adults with high status NCPB and may be involved in the biochemical progress that influences depressive symptoms.
Prediabetes is associated with loss of appendicular skeletal muscle mass and sarcopenia
Authors: Li Shuying , Mao Jiangfeng , Zhou Weihong 
Published: March 2023

BackgroundDecreasing mass and metabolism in skeletal muscle are associated with increasing insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The causal relation between sarcopenia and abnormal glucose metabolism may be bidirectional. This investigation is aimed to explore the detailed correlation between pre-diabetes and sarcopenia in United States (US) adults.MethodsA total of 22,482 adults aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) were included. Generalized linear models were conducted to examine associations between diabetes status, serum glucose, glycohemoglobin (HbA1c), and sarcopenia. Generalized additive models and smooth fitting curves were used to examine the non-linear relationship between HbA1c and ASMBMI. Sarcopenia was defined as ASMBMI (appendicular skeletal muscle mass/body mass index) &lt; 0.789 for males, and &lt;0.512 for females based on the cut-off values of the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project.ResultsAfter fully adjusting for multiple covariates, sarcopenia was directly correlated with pre-diabetes [OR (95%CI) = 1.230 (1.057, 1.431), p = 0.008] and T2DM [OR (95%CI) = 2.106 (1.625, 2.729), p &lt; 0.001]. In non-T2DM population, HbA1c was negatively correlated with ASMBMI [β (95%CI) = −0.009 (−0.013, −0.005), p &lt; 0.001]. The correlations only persisted in males. Furthermore, in male non-T2DM population, the association of HbA1c and ASMBMI presents an inverted U-shape curve with an inflection point of HbA1c 5.2%.ConclusionPre-diabetes is associated with increased risk of sarcopenia. HbA1c is an independent risk factor for loss of appendicular skeletal muscle mass and sarcopenia when HbA1c greater than 5.2% in the male non-T2DM population.
Comparison of the efficacy and safety of third-line treatments for advanced gastric cancer: A systematic review and network meta-analysis
Authors: Zhang Chan , Xiang Yaoxian , Wang Jing , Yan Dong 
Published: March 2023

BackgroundMany options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan.MethodsThe published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs).ResultsFive phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first.ConclusionsNivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022364714.
A CT based radiomics nomogram for differentiation between focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma
Authors: Lu Jia , Jiang Nannan , Zhang Yuqing , Li Daowei 
Published: March 2023

ObjectivesThe purpose of this study was to develop and validate an CT-based radiomics nomogram for the preoperative differentiation of focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.Methods96 patients with focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma have been enrolled in the study (32 and 64 cases respectively). All cases have been confirmed by imaging, clinical follow-up and/or pathology. The imaging data were considered as: 70% training cohort and 30% test cohort. Pancreatic lesions have been manually delineated by two radiologists and image segmentation was performed to extract radiomic features from the CT images. Independent-sample T tests and LASSO regression were used for feature selection. The training cohort was classified using a variety of machine learning-based classifiers, and 5-fold cross-validation has been performed. The classification performance was evaluated using the test cohort. Multivariate logistic regression analysis was then used to develop a radiomics nomogram model, containing the CT findings and Rad-Score. Calibration curves have been plotted showing the agreement between the predicted and actual probabilities of the radiomics nomogram model. Different patients have been selected to test and evaluate the model prediction process. Finally, receiver operating characteristic curves and decision curves were plotted, and the radiomics nomogram model was compared with a single model to visually assess its diagnostic ability.ResultsA total of 158 radiomics features were extracted from each image. 7 features were selected to construct the radiomics model, then a variety of classifiers were used for classification and multinomial logistic regression (MLR) was selected to be the optimal classifier. Combining CT findings with radiomics model, a prediction model based on CT findings and radiomics was finally obtained. The nomogram model showed a good sensitivity and specificity with AUCs of 0.87 and 0.83 in training and test cohorts, respectively. The areas under the curve and decision curve analysis showed that the radiomics nomogram model may provide better diagnostic performance than the single model and achieve greater clinical net benefits than the CT finding model and radiomics signature model individually.ConclusionsThe CT image-based radiomics nomogram model can accurately distinguish between focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma patients and provide additional clinical benefits.
EGCG identified as an autophagy inducer for rosacea therapy
Authors: Zhou Lei , Zhong Yun , Wang Yaling , Deng Zhili , Huang Yingxue , Wang Qian , Xie Hongfu , Zhang Yiya , Li Ji 
Published: March 2023

Background: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. In vivo and in vitro experiments were conducted to verify its therapeutic role. Drug–target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets.Results: WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the in vivo experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed in vivo and in vitro. Finally, drug–target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea.Conclusion: Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation via inducing autophagy in keratinocytes.
Smallholders’ knowledge about healing goat gastrointestinal parasite infections with wild plants in southern DR Congo
Authors: Mavungu Gaël Nzuzi , Mutombo Cedrick Shakalenga , Numbi Désiré Mujike , Nsenga Salvatora Nkulu , Muyumba Welcome Nonga , Pongombo Celestin Shongo , Bakari Salvius Amuri , Nachtergael Amandine , Vandenput Sandrina , Okombe Victor Embeya , Duez Pierre 
Published: March 2023

Gastrointestinal parasite (GIP) infections control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. This study aimed to collect indigenous knowledge and identify wild plants locally used by goat smallholders of three territories of Haut-Katanga province for treating signs of gastrointestinal parasitism. Ethnoveterinary surveys were conducted by semi-structured interviews and a bibliographic screening of the biological activities relating to cited plants was carried out. Our interviews showed that ethnosemantic diagnoses of GIP diseases are based on signs. Eighty-seven informants reported that 27 plant species from 15 families, dominated by Fabaceae (29.6%) and Lamiaceae (18.5%) were commonly used in their goats treatment. Among these plants, five species with palmately compound leaves were considerably more used. From those, we noted a substitution of Vitex congolensis De Wild. and T. Durand (Lamiaceae) by Oldfieldia dactylophylla (Welw. Ex Oliv.) J. Leonard (Picrodendraceae) and of Vitex mombassae Vatke by Vitex madiensis Oliv. Subsp. Milanjiensis (Britten) F. White. Roots (46.9%), leaves (28.0%) and seeds (12.5%) were the most frequently used plant organs, and maceration is applied for most of the medicinal preparations (62.2%). Recipes were administered by oral route, for GIP 1) prevention (33.3%), by macerating the ground plant material in drinking water for 2 weeks at the start of each season (dry and rainy); and 2) treatment (66.7%). According to the literature, some of these plants have few or no studies investigating their anthelmintic activity. The cited plants are worth investigating further as they could constitute an effective alternative strategy in maintaining animal productivity. Studies on the biological activity of these plants can also provide indications of promising leads for extracts that could be developed into commercial standardized medications.
Comparative pharmacokinetics of four major compounds after oral administration of Mori Cortex total flavonoid extract in normal and diabetic rats
Authors: Xiong Shan , Li Xiaofan , Chu Haiping , Deng Zhipeng , Sun Linying , Liu Jia , Mu Yanling , Yao Qingqiang 
Published: March 2023

Introduction: Mori Cortex has been used in traditional Chinese Medicine as an antidiabetic agent. The aim of this study was to establish a UPLC-MS/MS method for simultaneous determination of morin, morusin, umbelliferone and mulberroside A in rat plasma and investigate the pharmacokinetics differences between normal and diabetic rats following oral administration of Mori Cortex total flavonoid extract.Methods: Samples were pre-treated by protein precipitation and genkwanin was used as internal standard. Chromatographic separation was performed using a Hypersil GOLD C18 column (50 mm × 2.1 mm, 3 μm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) in gradient mode at a flow rate of 0.5 ml/min. The transitions of m/z 300.9→107.1, m/z 419.3→297.1, m/z 160.9→77.0, m/z 567.1→243.2 and m/z 283.1→268.2 were selected for morin, morusin, umbelliferone, mulberroside A and internal standard, respectively.Results: The intra- and inter-day precision for analytes were less than 12.5% and the accuracy ranged from −8.1% to 3.5%. The extraction recovery was &gt;88.5% and no obvious matrix effect was observed. The AUC(0-t) and Cmax of morin were 501.3 ± 115.5 ng/mL*h and 127.8 ± 56.0 ng/mL in normal rats and 717.3 ± 117.4 ng/ml*h and 218.6 ± 33.5 ng/ml in diabetic rats. Meanwhile, the AUC(0-t) and Cmax of morusin were 116.4 ± 38.2 ng/ml*h and 16.8 ± 10.1 ng/mL in normal rats and 325.0 ± 87.6 ng/mL*h and 39.2 ± 5.9 ng/ml in diabetic rats. For umbelliferone and mulberroside A, the AUC(0-t) and Cmax also increased significantly in diabetic rats (p &lt; 0.05).Discussion: The validated method was successfully applied to the pharmacokinetic study in normal and diabetic rats.