bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of genes co-associated with osteoporosis and chronic HBV infection based on bioinformatics analysis and machine learning
Authors: Yang Jia , Yang Weiguang , Hu Yue , Tong Linjian , Liu Rui , Liu Lice , Jiang Bei , Sun Zhiming 
Published: September 2024

ObjectiveTo identify HBV-related genes (HRGs) implicated in osteoporosis (OP) pathogenesis and develop a diagnostic model for early OP detection in chronic HBV infection (CBI) patients.MethodsFive public sequencing datasets were collected from the GEO database. Gene differential expression and LASSO analyses identified genes linked to OP and CBI. Machine learning algorithms (random forests, support vector machines, and gradient boosting machines) further filtered these genes. The best diagnostic model was chosen based on accuracy and Kappa values. A nomogram model based on HRGs was constructed and assessed for reliability. OP patients were divided into two chronic HBV-related clusters using non-negative matrix factorization. Differential gene expression analysis, Gene Ontology, and KEGG enrichment analyses explored the roles of these genes in OP progression, using ssGSEA and GSVA. Differences in immune cell infiltration between clusters and the correlation between HRGs and immune cells were examined using ssGSEA and the Pearson method.ResultsDifferential gene expression analysis of CBI and combined OP dataset identified 822 and 776 differentially expressed genes, respectively, with 43 genes intersecting. Following LASSO analysis and various machine learning recursive feature elimination algorithms, 16 HRGs were identified. The support vector machine emerged as the best predictive model based on accuracy and Kappa values, with AUC values of 0.92, 0.83, 0.74, and 0.7 for the training set, validation set, GSE7429, and GSE7158, respectively. The nomogram model exhibited AUC values of 0.91, 0.79, and 0.68 in the training set, GSE7429, and GSE7158, respectively. Non-negative matrix factorization divided OP patients into two clusters, revealing statistically significant differences in 11 types of immune cell infiltration between clusters. Finally, intersecting the HRGs obtained from LASSO analysis with the HRGs identified three genes.ConclusionThis study successfully identified HRGs and developed an efficient diagnostic model based on HRGs, demonstrating high accuracy and strong predictive performance across multiple datasets. This research not only offers new insights into the complex relationship between OP and CBI but also establishes a foundation for the development of early diagnostic and personalized treatment strategies for chronic HBV-related OP.
Case report: Recurrence of primary hepatic neuroendocrine tumors after resection of liver segments IV in 8 years follow-up
Authors: Li Chunli , Bian Li , Fan Guangtao , Huang Yilong , Li Jiang , He Bo 
Published: September 2024

BackgroundPrimary hepatic neuroendocrine tumors (PHNETs) are an utterly rare entity. The diagnosis of PHNETs could legitimize when an extrahepatic primary NET must always be excluded. PHNETs can achieve a high survival rate after complete surgical resection, however, most patients still have an 18% risk of recurrence within 5 years after surgery. In our case, the recurrence occurred 8 years after the first hepatectomy, which is relatively rare in the current literature. Therefore, rigorous postoperative follow-up is necessary for early detection and timely treatment of recurrent PHNETs.Case informationWe report a case of PHNET in a 24-year-old previously healthy female patient who relapsed 8 years after hepatectomy. This case focuses on the importance of diagnosis of primary and recurrent PHNETS in young patients, rare pathological types, and post-operative follow-up.ConclusionThis case report detailed the rare pathological morphology and characteristic immunohistochemical markers in our case for PHNETS, which enhanced the new understanding of the diagnosis of this entity. In addition, we also highlighted the variable duration of recurrence after treatment of PHNETs. The 8-year recurrent period in our case suggests the importance of regular examination in patients with PHNETs by following the doctor’s instructions.
The composition of the stent microbiome is associated with morbidity and adverse events during endoscopic drainage therapy of pancreatic necroses and pseudocysts
Authors: Frost Fabian , Khaimov Valeria , Senz Volkmar , Weiss Stefan , Klußmann-Fricke Bastian , Rühlemann Malte , Bang Corinna , Franke Andre , Pickartz Tilman , Budde Christoph , Aghdassi Ali A. , Siewert Stefan , Weiss Frank U. , Grabow Niels , Lerch Markus M. , Sendler Matthias 
Published: September 2024

BackgroundDevelopment of pancreatic necroses or pseudocysts are typical complications of pancreatitis and may require endoscopic drainage therapy using metal or plastic stents. Microbial infection of these lesions poses a major challenge. So far, the composition and significance of the microbial colonization on drainage stents are largely unknown although it may impact outcomes during endoscopic drainage therapy.MethodsA total of 26 stents used for drainage of pancreatic lesions were retrieved and the stent microbiome was determined by 16S rRNA gene sequencing. Additional analysis included comparison of the stent microbiome to the intracavitary necrosis microbiome as well as scanning electron microscopy (SEM) and micro-computed tomography (μCT) imaging of selected metal or plastic stents.ResultsThe stent microbiome comprises a large proportion of opportunistic enteric pathogens such as Enterococcus (14.4%) or Escherichia (6.1%) as well as oral bacteria like Streptococcus (13.1%). Increased levels of opportunistic enteric pathogens were associated with a prolonged hospital stay (r = 0.77, p = 3e−06) and the occurrence of adverse events during drainage therapy (p = 0.011). Higher levels of oral bacteria were associated (r = −0.62, p = 8e-04) with shorter durations of inpatient treatment. SEM and μCT investigations revealed complex biofilm networks on the stent surface.ConclusionThe composition of the stent microbiome is associated with prolonged hospital stays and adverse events during endoscopic drainage therapy, highlighting the need for effective infection control to improve patient outcomes. In addition to systemic antibiotic therapy, antimicrobial stent coatings could be a conceivable option to influence the stent microbiome and possibly enhance control of the necrotic microflora.
Transfer learning approach in pre-treatment CT images to predict therapeutic response in advanced malignant pleural mesothelioma
Authors: Fanizzi Annarita , Catino Annamaria , Bove Samantha , Comes Maria Colomba , Montrone Michele , Sicolo Angela , Signorile Rahel , Perrotti Pia , Pizzutilo Pamela , Galetta Domenico , Massafra Raffaella 
Published: September 2024

IntroductionMalignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter.MethodsWe proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression).ResultsThe performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively.ConclusionsThe proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness.
Bushen Huoxue formula attenuates lipid accumulation evoking excessive autophagy in premature ovarian insufficiency rats and palmitic acid-challenged KGN cells by modulating lipid metabolism
Authors: Li Tian , Wei Yao , Jiao Beibie , Hao Rui , Zhou Beibei , Bian Xinlan , Wang Peijuan , Zhou Yahong , Sun Xia , Zhang Jian 
Published: September 2024

IntroductionPremature ovarian insufficiency (POI) has affected about 3.7% of women of reproductive age and is a major factor contributing to infertility. Bushen Huoxue formula (BHF), a traditional Chinese medicine prescription, is clinically used to treat POI in China. This study aims to investigate the potential mechanisms of BHF in combating POI using corticosterone-induced rats and palmitic acid (PA)-challenged human ovarian granulosa cells (GCs).MethodsInitially, ultra performance liquid chromatography tandem mass spectrometry was employed to analyze the components of BHF. The pharmacodynamic parameters evaluated included body weight, ovaries index, and serum hormone in rats. Follicle numbers were observed using H&amp;E staining. Additionally, PCNA and TUNEL staining were used to assess GCs proliferation and apoptosis, respectively. Lipid accumulation and ROS levels were examined using Oil Red O and ROS staining. Protein expressions were determined by western blot. To probe mechanisms, cell viability and E2 levels in BHF-treated, PA-stimulated GCs were determined using MTT and ELISA, respectively. Cell apoptosis and ROS levels were assessed using TUNEL and ROS staining. Proteins related to lipid metabolism and autophagy in PA-stimulated GCs were studied using agonists.ResultsOur results shown that BHF effectively normalized serum hormone levels, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH). Concurrently, BHF also significantly reduced follicular atresia and promoted cell proliferation while inhibiting apoptosis in POI rats. Furthermore, BHF mitigated ovarian lipid accumulation by modulating lipid metabolism, which included reducing lipid synthesis (expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α), increasing lipid catabolism (expression of adipose triglyceride lipase), and enhancing lipid oxidation (expression of carnitine palmitoyl transferase 1A). Mechanistically, the therapeutic effects of BHF on POI were linked with alleviation of lipid deposition-induced reactive oxygen species (ROS) accumulation and excessive autophagy, corroborating the results in PA-challenged GCs. After treatment with elesclomol (a ROS inducer) and rapamycin (an autophagy inducer) in GCs, the effects of BHF were almost counteracted under model conditions.ConclusionThese findings suggest that BHF alleviates the symptoms of POI by altering lipid metabolism and reducing lipid accumulation-induced ROS and autophagy, offering evidence for BHF’s efficacy in treating POI clinically.
Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II
Authors: Li Dexin , Zhang Jingxin , Jin Yuxin , Zhu Yaoxuan , Lu Xiaoqing , Huo Xinmei , Pan Chunshui , Zhong Lijun , Sun Kai , Yan Li , Yan Lulu , Huang Ping , Li Quan , Han Jing-Yan , Li Yin 
Published: September 2024

BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.
The identification of potent dual-target monopolar spindle 1 (MPS1) and histone deacetylase 8 (HDAC8) inhibitors through pharmacophore modeling, molecular docking, molecular dynamics simulations, and biological evaluation
Authors: Hua Huilian , Guan Lixia , Pan Bo , Gao Junyi , Geng Yifei , Niu Miao-Miao , Li Zhiqin , Li Jindong 
Published: September 2024

BackgroundOverexpression of monopolar spindle 1 (MPS1) and histone deacetylase 8 (HDAC8) is associated with the proliferation of liver cancer cells, so simultaneous inhibition of both MPS1 and HDAC8 could offer a promising therapeutic approach for the treatment of liver cancer. Dual-targeted MPS1/HDAC8 inhibitors have not been reported.MethodsA combined approach of pharmacophore modeling and molecular docking was used to identify potent dual-target inhibitors of MPS1 and HDAC8. Enzyme inhibition assays were performed to evaluate the optimal compound with the strongest inhibitory activity against MPS1 and HDAC8. The selectivity of MPH-5 for MPS1 and HDAC8 was assessed on a panel of 68 kinases and other histone deacetylases. Subsequently, molecular dynamics (MD) simulation verified the binding stability of the optimal compound to MPS1 and HDAC8. Ultimately, in vitro cellular assays and in vivo antitumor assays evaluated the antitumor efficacy of the most promising compound for the treatment of hepatocellular carcinoma.ResultsSix dual-target compounds (MPHs 1–6) of both MPS1 and HDAC8 were identified from the database using a combined virtual screening protocol. Notably, MPH-5 showed nanomolar inhibitory effect on both MPS1 (IC50 = 4.52 ± 0.21 nM) and HDAC8 (IC50 = 6.07 ± 0.37 nM). MD simulation indicated that MPH-5 stably binds to both MPS1 and HDAC8. Importantly, cellular assays revealed that MPH-5 exhibited significant antiproliferative activity against human liver cancer cells, especially HepG2 cells. Moreover, MPH-5 exhibited low toxicity and high efficacy against tumor cells, and it overcomes drug resistance to some extent. In addition, MPH-5 may exert its antitumor effects by downregulating MPS1-driven phosphorylation of histone H3 and upregulating HDAC8-mediated K62 acetylation of PKM2. Furthermore, MPH-5 showed potent inhibition of HepG2 xenograft tumor growth in mice with no apparent toxicity and presented favorable pharmacokinetics.ConclusionThe study suggests that MPH-5 is a potent, selective, high-efficacy, and low-toxicity antitumor candidate for the treatment of hepatocellular carcinoma.
Eating disorders and health literacy in Germany: results from two representative samples of adolescents and adults
Authors: König Lars , Schröder Rebekka , Hamer Tim , Suhr Ralf 
Published: September 2024

IntroductionEating disorders are associated with substantial burden for the affected individuals including negative health outcomes and increased mortality. So far, prevention programs for eating disorders have yielded mixed results concerning their efficacy. Therefore, more targeted prevention programs need to be developed. Health literacy has been identified as a potential influencing factor of eating disorders. This study aimed at exploring the relationship between likely cases of eating disorders and health literacy, alongside additional sociodemographic factors.Materials and methodsTwo large samples of adults (N = 3,011) and adolescents (N = 1,021) representative of the German-speaking population in Germany were recruited. Likely cases of eating disorders were identified using the SCOFF questionnaire. Health literacy was assessed with the HLS-EU-Q16 questionnaire. Sociodemographic information, including age, gender, social status and level of education, and subjective body image were obtained. χ2-tests of independence were calculated to determine the association between the investigated constructs.ResultsSuspected eating disorders were more likely in female than male adolescents but were not related to gender in adults. Rates of suspected eating disorders increased with increasing age in adolescents and decreased with increasing age in adults. While levels of education were unrelated to suspected eating disorders, low social status was associated with higher rates of suspected eating disorders in adults but not adolescents. Inadequate or problematic health literacy and negative body image were associated with higher rates of suspected eating disorders compared to adequate health literacy and more positive body image.DiscussionLikely cases of eating disorders are related to health literacy and body image as well as sociodemographic factors. These constructs should therefore be addressed in future research to improve prevention programs.
Sexual and reproductive health service utilization and associated factors among youth workers at Kombolcha Industry Park, Kombolcha town, Northeast Ethiopia, 2023
Authors: Endalew Addisu , Kefale Bereket , Atnafu Gebeyehu Natnael , Birhan Belete 
Published: September 2024

BackgroundYouth is a decisive age that shapes the direction of their life and that of their family. However, due to the host of biological, social, and economic factors, youth Industry Park workers can be at high risk of adverse sexual and reproductive health outcomes. Therefore, assessing youth sexual and reproductive health service utilization and associated factors among youth workers is very crucial for timely intervention to their gaps.ObjectiveThis study aimed to assess sexual and reproductive health service utilization and associated factors among youth workers working at Kombolcha Industry Park Kombolcha, Northeast Ethiopia, 2023.MethodsAn institutional-based cross-sectional study was conducted at Kombolcha Industry Park, Kombolcha, among a total of 422 youth workers from 1 January to 30 January 2023. A simple random sampling technique was used to access a total of 422 youth workers in Kombolcha Industry Park. The data were collected using pre-test, structured, and interviewer-administered questionnaires. Data were entered into Epi Data version 3.1 and were exported to SPSS version 26 for analysis. Bi-variable and multivariable binary logistic regression analyses were performed. Adjusted odds ratio with 95% confidence interval was estimated to measure the strength of the association. The level of statistical significance was declared at a p value of less than 0.05.ResultsOverall utilization of reproductive health services was 45.50%. Being married [adjusted odds ratio (AOR) = 5.76, 95% CI (2.94, 11.25)], near distance of sexual and reproductive health (SRH) facility to home [AOR = 2.57, 95% CI (1.60, 4.14)], having good knowledge [AOR = 9.23 95%CI (4.88, 17.44)], and good attitude about SRH [AOR = 2.06 95% CI (1.29, 3.28)] were significantly associated with youth SRHs utilization.ConclusionYouth sexual and reproductive health service utilization among youth workers of Kombolcha Industry Park was low. Ensuring SRHs availability and accessibility, empowering youth with knowledge of SRHs, and advocating sexual and reproductive health services to develop a good attitude might be important in improving reproductive health service utilization. Future researchers should address segments of the population other than Kombolcha Industry Park.
EngageHealth: a mobile device application designed to deliver stroke rehabilitation exercises using asynchronous video recordings
Authors: Song Andrew J. , Lugo Leonel , Muccini Julie , Mlynash Michael , Lansberg Maarten G. 
Published: September 2024

BackgroundStroke survivors who receive more rehabilitation therapy achieve better functional outcomes. The amount of rehabilitation that patients receive is, however, limited due to constraints of the healthcare system.ObjectiveTo assess whether EngageHealth, a mobile device application designed to deliver stroke rehabilitation exercises using asynchronous video recordings, increases the amount of outpatient rehabilitation in stroke patients and improves their upper extremity function and quality of life.DesignProspective single-arm study consisting of a 2-week pre-intervention phase without EngageHealth followed by a 4-week intervention period with EngageHealth.SettingAmbulatory care.ParticipantsTwenty-four stroke patients with upper extremity impairment were recruited at the Stanford Stroke Center outpatient clinic.InterventionsParticipants were instructed to use the EngageHealth application daily.Main outcome measuresAdherence, user experience, and change in the upper extremity Fugl-Meyer (UE-FM), Quality of Life in Neurological Disorders (Neuro-QoL), and Stroke Impact Scale (SIS).ResultsOf 23 participants, five (22%) used the application for 17 days, six (26%) used the application for 9–16 days, and 12 (52%) used it &lt; 9 days. Sixty-three percent of participants would recommend the application to other stroke survivors, with fifty percent indicating they would continue using the application, if available. During the pre-intervention phase, there were no changes in hand function. During the intervention period, participants improved by 4 points on the UE-FM (P &lt; 0.01), and 15 points in the hand-function domain of SIS (P = 0.03). Videos of participants' exercises were successfully recorded, allowing the clinician to review videos of the participants' completed tasks asynchronously. In-depth interviews revealed that participants viewed the EngageHealth application favorably, and that their perceived usefulness of the exercises affected their motivation.ConclusionsUse of the EngageHealth application in the home environment may improve upper extremity function in subacute/chronic stroke patients. Additional support strategies should be implemented in future studies to improve adherence. These findings from a prospective single-arm study, support the design of a randomized controlled trial to determine the efficacy of long-term use of the EngageHealth application.