bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect modification by sex of genetic associations of vitamin C related metabolites in the Canadian Longitudinal study on aging
Authors: Lelievre Rebecca , Rakesh Mohan , Hysi Pirro G. , Little Julian , Freeman Ellen E. , Roy-Gagnon Marie-Hélène 
Published: July 2024

Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions.Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite.Results: Two genome-wide statistically significant (p value &lt; 5 × 10−8) interaction effects and several suggestive (p value &lt; 10–5) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2, associated with sex hormones, and AGRP, associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues.Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.
Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors
Authors: Ma Jingjing , Lin Zhiguang , Zhang Yaqi , Ding Yun , Tang Qiming , Qian Yufeng , Jin Bo , Luo Ruben Y. , Liao Wei-Li , Thyparambil Sheeno , Han Zhi , Chou C. James , Schilling James , Li Qing , Zhang Mengxue , Lin Yunan , Ma Yan , Sylvester Karl G. , Nagpal Seema , McElhinney Doff B. , Ling Xuefeng B. , Chen Bobin 
Published: July 2024

IntroductionPrimary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin’s lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.MethodsCSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.ResultsFinal proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.DiscussionThis study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
The effect of postpartum nursing guidance on early pelvic floor dysfunction recovery in women of advanced maternal age: a randomized controlled trial
Authors: Huang Qingyu , Tang Junfang , Zeng Dingyuan , Zhang Yu , Ying Ting 
Published: July 2024

ObjectiveThis study aimed to investigate the efficacy of postpartum nursing guidance in the treatment of early pelvic floor dysfunction (PFD) in women of advanced maternal age.MethodsA total of 146 patients of advanced maternal age admitted to our hospital between January and December 2021 were enrolled in this study and randomly divided into two groups: the control group and the experimental group, with 73 patients in each group. Parturients in the control group received routine pelvic floor rehabilitation treatment, whereas those in the experimental group were given individualized postpartum nursing guidance alongside routine pelvic floor rehabilitation treatment. The recovery of pelvic floor muscle (PFM) strength, the incidence of PFD diseases and nursing satisfaction were compared between the two groups after 3 months of treatment.ResultsThe enhancement of PFM strength in the experimental group significantly surpassed that in the control group. Furthermore, the experimental group exhibited a notably lower overall occurrence of PFD and significantly greater maternal satisfaction compared with the control group, and the difference was statistically significant (p &lt; 0.05).ConclusionCombining postpartum nursing guidance with pelvic floor rehabilitation for women of advanced maternal age represents a treatment regimen deserving of clinical endorsement, as it offers numerous advantages, including substantial improvement in PFM strength, decreased incidence of PFD and enhanced patient satisfaction.
More than red tape: exploring complexity in medical device regulatory affairs
Authors: Han Yu , Ceross Aaron , Bergmann Jeroen 
Published: July 2024

IntroductionThis study investigates the complexity of regulatory affairs in the medical device industry, a critical factor influencing market access and patient care.MethodsThrough qualitative research, we sought expert insights to understand the factors contributing to this complexity. The study involved semi-structured interviews with 28 professionals from medical device companies, specializing in various aspects of regulatory affairs. These interviews were analyzed using a mix of qualitative coding and natural language processing (NLP) techniques.ResultsThe findings reveal key sources of complexity within the regulatory landscape, divided into five domains: (1) regulatory language complexity, (2) intricacies within the regulatory process, (3) global-level complexities, (4) database-related considerations, and (5) product-level issues.DiscussionThe participants highlighted the need for strategies to streamline regulatory compliance, enhance interactions between regulatory bodies and industry players, and develop adaptable frameworks for rapid technological advancements. Emphasizing interdisciplinary collaboration and increased transparency, the study concludes that these elements are vital for establishing coherent and effective regulatory procedures in the medical device sector.
Genetic and causal relationship between chronic gastrointestinal diseases and erectile dysfunction: a Mendelian randomization study
Authors: Zeng Xiaoyan , Tong Li 
Published: July 2024

BackgroundStudies based on observations have indicated potential associations between chronic gastrointestinal diseases and an increased risk of erectile dysfunction (ED). However, the causality of these connections remains ambiguous.MethodsSummary data for chronic gastrointestinal diseases were extracted from public data. Summary data on ED were extracted from three distinct sources. The genetic correlations between chronic gastrointestinal diseases and ED were explored using linkage disequilibrium score regression (LDSC). The causal associations between chronic gastrointestinal diseases and ED were evaluated using Mendelian randomization (MR) analysis, followed by a meta-analysis to determine the ultimate causal effect.ResultsThe LDSC results suggested significant genetic correlations between Crohn's disease (CD) and ED. Inflammatory bowel disease (IBD), ulcerative colitis (UC), and liver cirrhosis (LC) were found to have potential genetic correlations with ED. The combined multiple MR results indicate that IBD and CD have significant causal relationships with ED, while colorectal cancer (CRC) may have a potential causal effect on ED.ConclusionThis research provided evidence supporting a causal association between IBD, CD, CRC, and ED. The impact of chronic gastrointestinal diseases on ED warrants greater attention in clinical practice.
Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing
Authors: Li Fu-Jia , Zhang Ru-Yu , Li Jin-Yu , Liu Yu-Ning , Zhang Zi-Xuan , Du Li , Li Yang-Dan-Yu , Liu Xu , Zhang Wei , Cui Gui-Yun , Xu Chuan-Ying 
Published: July 2024

ObjectivesThe objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders.MethodsIn stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis.ResultsIn stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)].ConclusionTriangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.
A computational model for potential microbe–disease association detection based on improved graph convolutional networks and multi-channel autoencoders
Authors: Zhang Chuyi , Zhang Zhen , Zhang Feng , Zeng Bin , Liu Xin , Wang Lei 
Published: July 2024

IntroductionAccumulating evidence shows that human health and disease are closely related to the microbes in the human body.MethodsIn this manuscript, a new computational model based on graph attention networks and sparse autoencoders, called GCANCAE, was proposed for inferring possible microbe–disease associations. In GCANCAE, we first constructed a heterogeneous network by combining known microbe–disease relationships, disease similarity, and microbial similarity. Then, we adopted the improved GCN and the CSAE to extract neighbor relations in the adjacency matrix and novel feature representations in heterogeneous networks. After that, in order to estimate the likelihood of a potential microbe associated with a disease, we integrated these two types of representations to create unique eigenmatrices for diseases and microbes, respectively, and obtained predicted scores for potential microbe–disease associations by calculating the inner product of these two types of eigenmatrices.Results and discussionBased on the baseline databases such as the HMDAD and the Disbiome, intensive experiments were conducted to evaluate the prediction ability of GCANCAE, and the experimental results demonstrated that GCANCAE achieved better performance than state-of-the-art competitive methods under the frameworks of both 2-fold and 5-fold CV. Furthermore, case studies of three categories of common diseases, such as asthma, irritable bowel syndrome (IBS), and type 2 diabetes (T2D), confirmed the efficiency of GCANCAE.
Characterization and transmission of plasmid-mediated multidrug resistance in foodborne Vibrio parahaemolyticus
Authors: Zhou Haibo , Lu Zhaoxin , Liu Xinmei , Bie Xiaomei , Cui Xinping , Wang Zuwei , Sun Xiaojie , Yang Jun 
Published: July 2024

ObjectivesThe purpose of this study was to determine the structural features and transferability of the multidrug-resistance (MDR) plasmid, and resistance phenotypes for the tested antimicrobials in foodborne Vibrio parahaemolyticus.MethodsPlasmids were isolated from a V. parahaemolyticus strain of seafood origin, then sequenced using the Illumina NovaSeq 6000 and PacBio Sequel II sequencing platforms to obtain the complete genome data. Characterization of the MDR plasmid pVP52-1, including determination of antimicrobial resistance genes (ARGs), plasmid incompatibility groups, and transferability, was carried out.ResultsV. parahaemolyticus strain NJIFDCVp52 contained two circular chromosomes and two circular plasmids (pVP52-1 and pVP52-2). Plasmid typing indicated that pVP52-1 belonged to the incompatibility group IncA/C2 and the sequence type pST3. pVP52-1 carried 12 different ARGs, an IS110-composite transposon consisting of aac(6′)-Ib-cr, qnrVC1, aac(6′)-Ib, dfrA14, and the IS26-mphA-IS6100 unit flanked by inverted sequences of IS5075 and IS4321. pVP52-2 carried no ARGs. A plasmid elimination assay showed that only pVP52-1 and its ARGs were lost, the loss of resistance to several antimicrobials, causing a change from the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-trimethoprim/sulfamethoxazole resistance pattern to the ampicillin resistance pattern. In accordance, a conjugation transfer assay showed that only pVP52-1 and its ARGs were horizontally transferred, leading to increased antimicrobial resistance in Escherichia coli strain EC600, causing a change from the ampicillin-nalidixic acid resistance pattern to the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-nalidixic acid-chloramphenicol-tetracycline-trimethoprim/sulfamethoxazole-azithromycin resistance pattern. Further transferability experiments revealed that pVP52-1 could be transferred to other enterobacterial strains of E. coli and Salmonella.DiscussionThis study emphasizes the urgent need for continued surveillance of resistance plasmids and changes in antimicrobial resistance profiles among the V. parahaemolyticus population.
Curing of chronic hepatitis C combined with coronavirus disease 2019 in a couple over 85 years old: a case series study
Authors: Zeng Qing-Lei , Lv Xue-Yan , Chen Ru-Yue , Pan Ya-Jie 
Published: July 2024

IntroductionData on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking.MethodsThe current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa®) and 5 days of nirmatrelvir/ritonavir (Paxlovid®) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment.ResultsIn late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient’s symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband’s HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife’s HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment.ConclusionThe older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment.DiscussionThis study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals.
Role of 14-3-3 protein family in the pathobiology of EBV in immortalized B cells and Alzheimer’s disease
Authors: Awasthi Prankur , Kumar Dhruv , Hasan Saba 
Published: July 2024

Background and AimsSeveral studies have revealed that Epstein-Barr virus (EBV) infection raised the likelihood of developing Alzheimer’s disease (AD) via infecting B lymphocytes. The purpose of the current investigation was to assess the possible association between EBV infection and AD.MethodsThe microarray datasets GSE49628, GSE126379, GSE122063, and GSE132903 were utilized to extract DEGs by using the GEO2R tool of the GEO platform. The STRING tool was used to determine the interaction between the DEGs, and Cytoscape was used to visualize the results. The DEGs that were found underwent function analysis, including pathway and GO, using the DAVID 2021 and ClueGo/CluePedia. By using MNC, MCC, Degree, and Radiality of cytoHubba, we identified seven common key genes. Gene co-expression analysis was performed through the GeneMANIA web tool. Furthermore, expression analysis of key genes was performed through GTEx software, which have been identified in various human brain regions. The miRNA–gene interaction was performed through the miRNet v 2.0 tool. DsigDB on the Enrichr platform was utilized to extract therapeutic drugs connected to key genes.ResultsIn GEO2R analysis of datasets with |log2FC|≥ 0.5 and p-value &lt;0.05, 8386, 10,434, 7408, and 759 genes were identified. A total of 141 common DEGs were identified by combining the extracted genes of different datasets. A total of 141 nodes and 207 edges were found during the PPI analysis. The DEG GO analysis with substantial alterations disclosed that they are associated to molecular functions and biological processes, such as positive regulation of neuron death, autophagy regulation of mitochondrion, response of cell to insulin stimulus, calcium signaling regulation, organelle transport along microtubules, protein kinase activity, and phosphoserine binding. Kyoto Encyclopedia of Genes and Genomes analysis discovered the correlation between the DEGs in pathways of neurodegeneration: multiple disease, cell cycle, and cGMP-PKG signaling pathway. Finally, YWHAH, YWHAG, YWHAB, YWHAZ, MAP2K1, PPP2CA, and TUBB genes were identified that are strongly linked to EBV and AD. Three miRNAs, i.e., hsa-mir-15a-5p, hsa-let-7a-5p, and hsa-mir-7-5p, were identified to regulate most of hub genes that are associated with EBV and AD. Further top 10 significant therapeutic drugs were predicted.ConclusionWe have discovered new biomarkers and therapeutic targets for AD, as well as the possible biological mechanisms whereby infection with EBV may be involved in AD susceptibility for the first time.
Cortical compensation mechanism for swallowing recovery in patients with medullary infarction-induced dysphagia
Authors: Gu Furong , Han Jing , Zhang Qiang , Li Xiangyu , Wang Yue , Wu Jialing 
Published: July 2024

IntroductionThis study aims to examine brain activity during different swallowing actions in patients with dysphagia caused by medullary infarction (MI) before and after treatment using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging.MethodsFifteen patients were enrolled in this study. Brain activation during saliva swallowing and effortful saliva swallowing was observed using BOLD imaging in the acute phase of stroke and after 4 weeks of rehabilitation training. Differences in the activation of brain regions during saliva swallowing before and after treatment, during effortful saliva swallowing before and after treatment, and between the two swallowing actions before and after treatment were compared.ResultsIn the acute phase of stroke, only the bilateral precentral and left lingual gyrus were partially activated during saliva swallowing, and there was no obvious activation in the insula. Effortful saliva swallowing activated more brain regions than saliva swallowing before treatment, including the bilateral supplementary motor area (SMA), postcentral gyrus, and right insular cortex. The number of brain regions activated during saliva swallowing increased after treatment, including the bilateral precentral gyrus, postcentral gyrus, insula, thalamus, and SMA.DiscussionCortical activation increases after recovery from dysphagia, and the increased activation of the postcentral gyrus might play a functional compensatory role. Effortful saliva swallowing is a more effective rehabilitation training method for patients with dysphagia caused by MI.
Ginkgo biloba extract prescriptions are associated with less frequent repeat visits to ENT doctors due to tinnitus: a retrospective cohort study
Authors: Langguth Berthold , Reineke Thorsten , Burkart Martin , Kostev Karel 
Published: July 2024

ObjectivesWe aimed to evaluate the drug utilization of Ginkgo biloba extract (Gbe), systemic corticosteroids (CSs), and pentoxifylline (PTXF) for the treatment of acute tinnitus by analyzing electronic patient health record data. In addition, we assessed whether the different drug treatments were associated with different frequencies of repeat visits to ear, nose, and throat (ENT) doctors.MethodsThis retrospective cohort study used data from the IQVIA Disease Analyzer (DA) database. It included patients with an initial diagnosis of tinnitus between January 2005 and December 2021, treated by ENT specialists in Germany.ResultsOf 111,629 patients meeting all selection criteria, 51,205 received prescriptions of Gbe, 34,817 of systemic CSs, and 25,607 of PTXF. Gbe prescription was associated with significantly lower odds of a repeat consultation due to tinnitus compared to systemic CSs [odds ratio (OR) 0.91; 95% confidence interval (CI): 0.88–0.95] as well as PTXF (OR 0.74; 95% CI: 0.72–0.77). This association was significant in both men and women and in some age groups.ConclusionGbe is the most frequently ENT specialist-prescribed drug for the treatment of acute tinnitus. It is associated with a reduced likelihood of patients consulting their ENT specialist for tinnitus again compared to systemic CSs and PTXF.