bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic insights into the gut microbiota, herpes zoster, and postherpetic neuralgia: a bidirectional two-sample Mendelian randomization study
Authors: Deng Zhimin , Liu Yali , Wang Haiying , Luo Tianyuan 
Published: May 2024

BackgroundAn increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut microbiota may play a crucial role in this process. Therefore, this study aims to explore the potential causal association between the gut microbiota and HZ and PHN.MethodsBidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between HZ and PHN and the gut microbiota. Gut microbiota data were derived from the MiBioGen consortium, while HZ and PHN data were obtained from the FinnGen database. We selected single-nucleotide polymorphisms (SNPs) as instrumental variables with a threshold of p &lt; 1 × 10⁻⁵ for the association with the gut microbiota in forward MR analysis and p &lt; 5 × 10⁻8 for the association with HZ or PHN in reverse MR analysis and then removed SNPs in linkage disequilibrium (r2 &lt; 0.001) within a distance of 10,000 kb for both the gut microbiota and HZ and PHN. These SNPs were utilized to assess the causal effect between exposures and outcomes using inverse-variance weighting (IVW), MR–Egger, weighted mean, and weighted median tests.ResultsThe class Deltaproteobacteria, order Desulfovibrionales, family Desulfovibrionaceae, and genus Coprococcus 2 were found to reduce the risk of HZ, while the phylum Cyanobacteria, genus Eubacterium rectale group appeared to increase it. The class Coriobacteriia, order Coriobacteriales, family Coriobacteriaceae, genus Lachnospiraceae NK4A136 and genus Ruminococcaceae UCG011 were found to reduce the risk of PHN, while the genus Candidatus Soleaferrea, genus Eubacterium rectale group, and genus Methanobrevibacter appeared to increase it. Moreover, the onset of HZ was found to increase the level of the genus Eubacterium rectale group. These findings remained robust and unaffected by heterogeneity or horizontal pleiotropy among SNPs in both forward and reverse MR analysis.ConclusionThis MR study provided evidence supporting a potential causal relationship between the gut microbiota and HZ and PHN. Moreover, we found that the causal effect between the gut microbiota and HZ is bidirectional. Further studies are required to clarify the biological mechanisms linking the gut microbiota and these conditions.
Specific feature recognition on group specific networks (SFR-GSN): a biomarker identification model for cancer stages
Authors: Chen Bolin , Wang Yuxin , Zhang Jinlei , Han Yourui , Benhammouda Hamza , Bian Jun , Kang Ruiming , Shang Xuequn 
Published: May 2024

Background and ObjectiveAccurate identification of cancer stages is challenging due to the complexity and heterogeneity of the disease. Current clinical diagnosis methods primarily rely on phenotypic observations, which may not capture early molecular-level changes accurately.MethodsIn this study, a novel biomarker recognition method was proposed tailored for cancer stages by considering the change of gene expression relationships. Utilizing the sample-specific information and protein-protein interaction networks, the group specific networks were constructed to address the limited specificity of potential biomarkers. Then, a specific feature recognition method was proposed based on these group specific networks, which employed the random forest algorithm for initial screening followed by a recursive feature elimination process to identify the optimal biomarker subset. During exploring optimal results, a strategy termed the Cost-Benefit Ratio, was devised to facilitate the identification of stage-specific biomarkers.ResultsComparative experiments were conducted on lung adenocarcinoma and breast cancer datasets to validate the method’s efficacy and generalizability. The results showed that the identified biomarkers were highly stage-specific, and the F1 scores for predicting cancer stages were significantly improved. For the lung adenocarcinoma dataset, the F1 score reached 97.68%, and for the breast cancer dataset, it achieved 96.87%. These results significantly surpassed those of three conventional methods in terms of F1 scores. Moreover, from the perspective of biological functions, the biomarkers were proved playing an important role in cancer stage-evolution.ConclusionThe proposed method demonstrated its effectiveness in identifying stage-related biomarkers. By using these biomarkers as features, accurate prediction of cancer stages was achieved. Furthermore, the method exhibited potential for biomarker identification in subtype analyses, offering novel perspectives for cancer prognosis.
Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis
Authors: Yang Yue , Zou Gu-ming , Wei Xian-sen , Zhang Zheng , Zhuo Li , Xu Qian-qian , Li Wen-ge 
Published: May 2024

BackgroundMembranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive.MethodsIn this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer.ResultsWe conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers.ConclusionThis evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.
Recurrent CNTN1 antibody-positive nodopathy: a case report and literature review
Authors: Zhao Min , Chen Guixian , Li Shuguang , Li Xiaojun , Chen Haoxuan , Lou Zhenzhen , Ouyang Huiying , Zhan Yibo , Du Chenghao , Zhao Yuanqi 
Published: May 2024

BackgroundContactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown.Case presentationHere, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment’s efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L.ConclusionWe present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.
Anti-RBD IgG antibodies from endemic coronaviruses do not protect against the acquisition of SARS-CoV-2 infection among exposed uninfected individuals
Authors: Adami Flávia Lopes , de Castro Mateus Vidigal , Almeida Bianca da Silva , Daher Isabela Pazotti , Yamamoto Márcio Massao , Souza Santos Keity , Zatz Mayana , Naslavsky Michel Satya , Rosa Daniela Santoro , Cunha-Neto Edecio , de Oliveira Vivian Leite , Kalil Jorge , Boscardin Silvia Beatriz 
Published: May 2024

BackgroundThe Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases. An essential question since the onset of the COVID-19 pandemic has been to determine whether prior exposure to seasonal coronaviruses influences immunity or protection against SARS-CoV-2.MethodsIn this study, we investigated a cohort of 47 couples (N=94), where one partner tested positive for SARS-CoV-2 infection via real-time PCR while the other remained negative. Plasma samples, collected at least 30 days post-PCR reaction, were assessed using indirect ELISA and competition assays to measure specific antibodies against the receptor-binding domain (RBD) portion of the Spike (S) protein from SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1.ResultsIgG antibody levels against the four endemic coronavirus RBD proteins were similar between the PCR-positive and PCR-negative individuals, suggesting that IgG against endemic coronavirus RBD regions was not associated with protection from infection. Moreover, we found no significant IgG antibody cross-reactivity between endemic coronaviruses and SARS-CoV-2 RBDs.ConclusionsTaken together, results suggest that anti-RBD antibodies induced by a previous infection with endemic HCoVs do not protect against acquisition of COVID-19 among exposed uninfected individuals.
Efficacy and safety of intravitreal injection of conbercept for moderate to severe nonproliferative diabetic retinopathy
Authors: Shen Lu , Zheng Yuxiang , Gao Zelan , Li Qirui , Dai Min , Yang Wenchang , Zhang Qiying , Li Dongli , Hu Yijun , Yuan Ling 
Published: May 2024

PurposeThis study aimed to assess the effectiveness and safety of intravitreal injection of conbercept (IVC) in treating moderate to severe nonproliferative diabetic retinopathy (NPDR), with or without accompanying diabetic macular edema.MethodsIn this longitudinal retrospective study, 35 patients (50 eyes) with moderate to severe NPDR and Diabetic Retinopathy Severity Scale (DRSS) scores between 43 and 53 were treated at the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, from October 2018 to January 2023. Treatment protocol included three monthly IVC injections followed by a pro re nata (PRN) regimen over a two-year follow-up period. Outcome measures were best-corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), extent of hard exudate (HE), and changes in DRSS scores. DRSS scores before and after treatment were analyzed using the Wilcoxon rank-sum test. Both systemic and ocular adverse events were meticulously documented to ascertain safety.ResultsFrom baseline to the final follow-up, the mean BCVA improved from 0.41 ± 0.39 to 0.23 ± 0.20 logMAR (p&lt;0.05). The mean CMT decreased from 306.22 ± 77.40 to 297.97 ± 88.15 μm (p = 0.385). At 24 months, DRSS scores improved by ≥1 stage in 40 eyes (80%), ≥ 2 stages in 28 eyes (56%), ≥3 stages in 10 eyes (20%), and remained stable in 6 eyes (12%). The DRSS scores at each follow-up interval demonstrated statistically significant improvement from baseline (p&lt;0.05). In 15 of 27 eyes (55.56%) with diabetic macular edema (DME), there was a significant reduction in the mean area of HE from baseline (p&lt;0.05). No serious systemic adverse events were observed.ConclusionIVC is an effective and safe treatment for moderate to severe NPDR, demonstrating significant improvements in DRSS scores.
Hypervirulent Klebsiella pneumoniae in a South African tertiary hospital—Clinical profile, genetic determinants, and virulence in Caenorhabditis elegans
Authors: Dingiswayo Likhona , Adelabu Olusesan Adeyemi , Arko-Cobbah Emmanuel , Pohl Carolina , Mokoena Nthabiseng Zelda , Du Plessis Morne , Musoke Jolly 
Published: May 2024

IntroductionA distinct strain of Klebsiella pneumoniae (K. pneumoniae) referred to as hypervirulent (hvKp) is associated with invasive infections such as pyogenic liver abscess in young and healthy individuals. In South Africa, limited information about the prevalence and virulence of this hvKp strain is available. The aim of this study was to determine the prevalence of hvKp and virulence-associated factors in K. pneumoniae isolates from one of the largest tertiary hospitals in a South African province.MethodsA total of 74 K. pneumoniae isolates were received from Pelonomi Tertiary Hospital National Health Laboratory Service (NHLS), Bloemfontein. Virulence-associated genes (rmpA, capsule serotype K1/K2, iroB and irp2) were screened using Polymerase Chain Reaction (PCR). The iutA (aerobactin transporter) gene was used as a primary biomarker of hvKp. The extracted DNAs were sequenced using the next-generation sequencing pipeline and the curated sequences were used for phylogeny analyses using appropriate bioinformatic tools. The virulence of hvKp vs. classical Klebsiella pneumoniae (cKp) was investigated using the Caenorhabditis elegans nematode model.ResultsNine (12.2%) isolates were identified as hvKp. Moreover, hvKp was significantly (p &lt; 0.05) more virulent in vivo in Caenorhabditis elegans relative to cKp. The virulence-associated genes [rmpA, iroB, hypermucoviscous phenotype (hmv) phenotype and capsule K1/K2] were significantly (p &lt; 0.05) associated with hvKp. A homology search of the curated sequences revealed a high percentage of identity between 99.8 and 100% with other homologous iutA gene sequences of other hvKp in the GenBank.ConclusionFindings from this study confirm the presence of hvKp in a large tertiary hospital in central South Africa. However, the low prevalence and mild to moderate clinical presentation of infected patients suggest a marginal threat to public health. Further studies in different settings are required to establish the true potential impact of hvKp in developing countries.
Responsiveness and construct validity of two outcome measures of bilateral upper limb function in patients with chronic stroke
Authors: Tsai Han-ting , Lau Hiu-ying , Lin Keh-chung , Li Yi-chun , Lin Chia-jung , Yao Grace , Lee Ya-yun , Chen Wen-shiang , Chen Chia-ling , Chang Ya-ju , Horng Yi-shiung 
Published: May 2024

BackgroundStroke is a leading cause of long-term disability among stroke survivors. Despite the availability of numerous stroke rehabilitative therapies, such as mirror therapy, bilateral arm training, and robot-assisted therapy, the recovery of motor function after stroke remains incomplete. Bilateral arm function is a key component in stroke patients to perform activities of daily living and to reflect their functional autonomy.ObjectiveThis clinimetric study investigated and compared the construct validity and responsiveness of 2 bimanual activity outcome measures, the Chedoke Arm and Hand Activity Inventory (CAHAI) and the ABILHAND Questionnaire, in individuals receiving stroke rehabilitation.MethodsThe present study is a secondary analysis following the framework of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Individuals with chronic stroke (N = 113) were recruited from outpatient rehabilitation settings. Participants received 18 to 20 sessions of robot-assisted therapy, mirror therapy, combined therapy, or conventional rehabilitation for 4 to 6 weeks. The CAHAI, ABILHAND Questionnaire, and a comparison instrument, the Motor Activity Log (MAL), were administered twice at a 4- to 6-week interval to all participants. ABILHAND scores, in logits, were converted from raw ordinal scores into a linear measure.ResultsThere was medium to large correlation of the CAHAI and the MAL (ρ = 0.60–0.62, p &lt; 0.01) as well as the ABILHAND Questionnaire and the MAL (ρ = 0.44–0.51, p &lt; 0.01). Change scores from the initial measurement to the post-intervention measurement demonstrated small to medium correlation of the CAHAI and the MAL (ρ = 0.27–0.31, p &lt; 0.01) and medium to large correlation of the ABILHAND Questionnaire and the MAL (ρ = 0.37–0.41, p &lt; 0.01). Overall, 7 of 8 hypotheses were supported. The hypothesis testing regarding the construct validity and responsiveness of the CAHAI and ABILHAND Questionnaire was confirmed.ConclusionThe CAHAI and ABILHAND Questionnaire are both responsive and suitable to detect changes in bilateral arm functional daily activities in individuals with chronic stroke. Patient-reported outcome measures are recommended to use along with therapist-rated outcome measures for upper limb capacity evaluation in stroke rehabilitation. Further study with a prospective study design to capture specific clinical features of participants and the use of body-worn sensors, such as the arm accelerometer, is suggested.
Risk factors for the development of cervical cancer: analysis of the evidence
Authors: Luvián-Morales Julissa , Gutiérrez-Enríquez Sandra Olimpia , Granados-García Víctor , Torres-Poveda Kirvis 
Published: May 2024

IntroductionCervical cancer (CC) is the fourth most prevalent female cancer globally. Understanding its epidemiology is crucial for devising practical strategies suited to geographic and social contexts to attain the global eradication of CC. Hence, this study examined the latest evidence of risk factors contributing to CC development.MethodsAn independent literature search was conducted on PubMed using MESH terms. The primary sources were meta-analyses published from 2010 to 2023, which detail updated evidence on risk factors associated with CC. Additionally, the quality of the evidence was evaluated using the GRADE system and recommendations were made accordingly.ResultsThe main risk factors related to the cause of CC include co-infections with other sexually transmitted infections, genetic markers, cervicovaginal microbiota, nutritional factors, comorbidities that affect the immune response, smoking, and the use of hormonal contraceptives with a quality evidence based on the GRADE scale moderate.ConclusionsSince the necessary cause for CC is persistent cervicovaginal HPV, all the risk factors implicated in the causality of CC act as non-independent cofactors that increase the risk of CC. Thus, changes in public policies aimed at addressing these risk factors are highly recommended and can substantially decrease the risk of CC.
Impact of metformin on melanoma: a meta-analysis and systematic review
Authors: Feng Hua , Shang Shuxian , Chen Kun , Sun Xuan , Yue Xueping 
Published: May 2024

BackgroundThere is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.MethodsSelection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.ResultsA total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.DiscussionThe improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.