bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis
Authors: Xie Qinghui , Tang Yijie , Shen Lingyun , Yang Dandan , Zhang Jiaqin , Luo Qingqiong 
Published: April 2024

BackgroundInfection with Treponema pallidum instigates complex immune responses. Prior research has suggested that persistent Treponema pallidum infection can manipulate host immune responses and circumvent host defenses. However, the precise role of immune cells in Treponema pallidum infection across different stages remains a contentious issue.MethodsUtilizing summary data from genome-wide association studies, we employed a two-sample Mendelian randomization method to investigate the association between 731 immunophenotypes and syphilis. Syphilis was categorized into early and late stages in this study to establish a more robust correlation and minimize bias in database sources.ResultsOur findings revealed that 33, 36, and 27 immunophenotypes of peripheral blood were associated with syphilis (regardless of disease stage), early syphilis and late syphilis, respectively. Subsequent analysis demonstrated significant variations between early and late syphilis in terms of immunophenotypes. Specifically, early syphilis showcased activated, secreting, and resting regulatory T cells, whereas late syphilis was characterized by resting Treg cells. More B cells subtypes emerged in late syphilis. Monocytes in early syphilis exhibited an intermediate and non-classical phenotype, transitioning to classical in late syphilis. Early syphilis featured naive T cells, effector memory T cells, and terminally differentiated T cells, while late syphilis predominantly presented terminally differentiated T cells. Immature myeloid-derived suppressor cells were evident in early syphilis, whereas the dendritic cell immunophenotype was exclusive to late syphilis.ConclusionMultiple immunophenotypes demonstrated associations with syphilis, showcasing substantial disparities between the early and late stages of the disease. These findings hold promise for informing immunologically oriented treatment strategies, paving the way for more effective and efficient syphilis interventions.
Paradoxical reaction to IL-17A inhibitor: a case report and literature review
Authors: Ren Jingyu , Deng Linjun , Guo Shuping , Liu Hongye 
Published: April 2024

ObjectiveA case of pustular psoriasis after treatment with secukinumab in a patient with plaque psoriasis is reported, which is the first case in China. To summarize the clinical characteristics of patients who developed the rare paradoxical reaction and treatment options received IL-17A antagonist therapy, we conducted a further literature review.MethodsData were analyzed from a patient with plaque psoriasis who developed pustular psoriasis after treatment with secukinumab. A comprehensive review of relevant domestic and international literature was conducted, focusing on cases that met our inclusion criteria for analysis and synthesis.ResultsAnti IL-17A therapy may lead to type conversion, with reported cases more prevalent in women and varying in onset time, predominantly involving palmoplantar pustulosis.ConclusionGiven the increasing use of IL-17A antagonists in psoriasis treatment, it is crucial to monitor for rare adverse reactions, including the paradoxical induction of pustular psoriasis.
Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study
Authors: Zhao Zirui , Xu Zhongye , Lv Dongming , Rong Yanchao , Hu Zhicheng , Yin Rong , Dong Yunxian , Cao Xiaoling , Tang Bing 
Published: April 2024

ObjectiveSkin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis.MethodsWe retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results.ResultsAccording to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.Objective conclusionThere is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.
The creation of an adaptable informed consent form for research purposes to overcome national and institutional bottlenecks in ethics review: experience from rare disease registries
Authors: Landi Annalisa , Mimouni Yanis , Giannuzzi Viviana , Schaefer Franz , Altavilla Annagrazia , Gibson Spencer , Julkowska Daria 
Published: April 2024

BackgroundThe lack of harmonization of evaluation criteria by Ethics Committees in the European Union (EU) has led to inconsistent ethics reviews received by research sites participating in multicenter non-interventional studies. The European General Data Protection Regulation (GDPR) appears to be implemented at national level with a substantial degree of variance in interpretation. The European Reference Networks (ERNs) were struggling in setting an Informed Consent Form (ICF) for registries, allowing reuse of data for research purposes. The aim of this work is to develop an adaptable ICF for research purposes to be used in ERN registries.MethodsTo work on this challenge, a team was established within the European Joint Programme on Rare Diseases (EJP RD) to develop a patients’ registry ICF template allowing easy adaptation to ERNs, country, and site-level specificities. ERN and patients’ representatives validated the choice of developing a GDPR-compliant template for research purposes. The feedback received from 34 Ethics Committees on the Clinical Patient Management System ICF, including the submission of patients’ data to the ERN registries and the EU consent regulatory framework were analyzed along with existing ontologies for data access and reuse. An adaptable ICF was developed following iterative cycles of consultation and review by clinicians, research experts, ethics and regulatory advisors, and patients’ representatives. The development of pediatric material for minor participants was also undertaken.Results and ConclusionResearch oriented ICF templates for adults and for parents/legal representatives of patients were released in 26 national languages. This adaptable ICF aims to foster, according to patients’ preferences, the reuse of registries data for research purposes in compliance with the applicable laws and standards. Pediatric material is being finalized to collect minors’ assent. ICF machine-readability is also progressing to enhance data discovery and facilitate its access and reuse conditions.
Upper limb motor assessment for stroke with force, muscle activation and interhemispheric balance indices based on sEMG and fNIRS
Authors: Ye Sijia , Tao Liang , Gong Shuang , Ma Yehao , Wu Jiajia , Li Wanyi , Kang Jiliang , Tang Min , Zuo Guokun , Shi Changcheng 
Published: April 2024

IntroductionUpper limb rehabilitation assessment plays a pivotal role in the recovery process of stroke patients. The current clinical assessment tools often rely on subjective judgments of healthcare professionals. Some existing research studies have utilized physiological signals for quantitative assessments. However, most studies used single index to assess the motor functions of upper limb. The fusion of surface electromyography (sEMG) and functional near-infrared spectroscopy (fNIRS) presents an innovative approach, offering simultaneous insights into the central and peripheral nervous systems.MethodsWe concurrently collected sEMG signals and brain hemodynamic signals during bilateral elbow flexion in 15 stroke patients with subacute and chronic stages and 15 healthy control subjects. The sEMG signals were analyzed to obtain muscle synergy based indexes including synergy stability index (SSI), closeness of individual vector (CV) and closeness of time profile (CT). The fNIRS signals were calculated to extract laterality index (LI).ResultsThe primary findings were that CV, SSI and LI in posterior motor cortex (PMC) and primary motor cortex (M1) on the affected hemisphere of stroke patients were significantly lower than those in the control group (p &lt; 0.05). Moreover, CV, SSI and LI in PMC were also significantly different between affected and unaffected upper limb movements (p &lt; 0.05). Furthermore, a linear regression model was used to predict the value of the Fugl-Meyer score of upper limb (FMul) (R2 = 0.860, p &lt; 0.001).DiscussionThis study established a linear regression model using force, CV, and LI features to predict FMul scale values, which suggests that the combination of force, sEMG and fNIRS hold promise as a novel method for assessing stroke rehabilitation.
Prevalence and influencing factors of malnutrition in stroke patients with bulbar paralysis: a cross-sectional study in China
Authors: Zeng Hongji , Liu Lianlian , Cai Ang , Zhao Weijia , Liu Yahui , Wang Liugen , Li Heping , Zeng Xi 
Published: April 2024

BackgroundAlthough malnutrition has been shown to influence the clinical outcomes of Stroke Patients with Bulbar Paralysis (SPBP), the prevalence and influencing factors have yet to be uncovered.ObjectiveThis study aims to assess the current prevalence and factors associated with malnutrition in SPBP.MethodsA multicenter cross-sectional investigation was conducted among SPBP in China from 2019 to 2021. Information was collected on basic information, health condition, diagnosis, treatment, neurological function, activities of daily living, swallowing function, and nutritional status. A multivariable logistic regression model was used to identify the factors that influenced nutritional status. ROC analysis was used to assess the predictive value of each independent influencing factor and the logit model.ResultsIn total, 774 SPBP were enrolled, and the prevalence of malnutrition was 60.59%. Pulmonary infection [aOR:2.849, 95%CI: (1.426, 5.691)], hemoglobin [aOR: 0.932, 95%CI: (0.875, 0.982)], serum albumin [aOR: 0.904, 95%CI: (0.871, 0.938)], total protein [aOR: 0.891, 95%CI: (0.819, 0.969)], prealbumin [aOR: 0.962, 95%CI: (0.932, 0.993)], and National Institute of Health Stroke Scale (NIHSS) scores [aOR: 1.228, 95%CI: (1.054, 1.431)] were independent factors associated with malnutrition in SPBP. ROC analysis revealed that the logit model had the best predictive value [area under the curve: 0.874, 95% CI: (0.812, 0.936); specificity: 83.4%; sensitivity: 79.3%; p &lt; 0.05]. Subgroup analysis showed that the nutritional status in dysphagic SPBP was additionally influenced by swallowing function and nutrition support mode.ConclusionThe prevalence of malnutrition in SPBP was 60.59%. Pulmonary infection, hemoglobin level, and NIHSS score were the independent factors associated with malnutrition. Swallowing function and nutrition support mode were the factors associated with malnutrition in dysphagic SPBP.
Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis
Authors: Cao Yuxuan , Liu Xinbo , Liu Jiayi , Su Ziyi , Liu Wenxuan , Yang Lei , Zhang Liwen 
Published: April 2024

BackgroundLung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis.MethodsFor this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed.ResultsThe study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86.ConclusionOur study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.
Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey
Authors: Tam Victor C. W. , Ching Jerry C. F. , Yip Sindy S. T. , Kwong Virginia H. Y. , Chan Catherine P. L. , Wong Kenneth C. W. , Lee Shara W. Y. 
Published: April 2024

IntroductionAlongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors’ quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors.MethodsA single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head &amp; Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head &amp; Neck (FACT-HN-C), and a question extracted from the Cancer Survivors’ Unmet Needs Measure (CaSUN).ResultsTwo hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 – 1.914, p &lt; 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 – 1.604, p &lt; 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p &lt; 0.001).ConclusionVirtually all NPC survivors suffer from late toxicities, which interplay with survivors’ perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.
Cabozantinib in combination with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis
Authors: Su Jingyang , Zhang Jialin , Wu Yuqian , Ni Cui , Ding Yueyue , Cai Zelin , Xu Ming , Lai Mingyang , Wang Jue , Lin Shengyou , Lu Jinhua 
Published: April 2024

ContextCabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC).ObjectivesWe performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC.MethodsWe extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials.ResultsA total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p &lt; 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p &lt; 0.0001].ConclusionCabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events.Systematic Review Registration:identifier CRD42023455878.
Real-world pharmacological treatment of pregnant patients with rheumatic diseases from China: a retrospective analysis from 2016 to 2021
Authors: Jia Ji-Ning , Wang Xian-Li 
Published: April 2024

Introduction: We investigated trends in the use of therapeutic drugs for pregnant patients with rheumatic diseases in nine Chinese cities (Beijing, Chengdu, Guangzhou, Harbin, Hangzhou, Shanghai, Shenyang, Tianjin, and Zhengzhou) to provide a reference for drug use in clinic.Methods: Outpatient prescription data for pregnant patients diagnosed with rheumatic diseases in nine cities across China in 2016–2021 were extracted from the Hospital Prescription Cooperation Project of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. A retrospective analysis was then performed, incorporating data on patient age, defined daily doses (DDDs), defined daily cost (DDC), and other metrics.Results: In 2016–2020, more than 70% of the pregnant patients diagnosed with rheumatic diseases in these nine cities were 25 to &lt; 35 years of age. The most common rheumatic diseases during pregnancy were antiphospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE). In terms of the routine use of daily therapeutic drugs, the DDDs of low molecular weight heparins (LMWHs), glucocorticoids, and immunosuppressive agents dominated the top three. Intravenous immunoglobulin (IVIG) and tumor necrosis factor inhibitors (TNFi) have been used since 2019 and had been in the forefront of the DDC.Conclusion: The number and total cost of prescriptions for therapeutic drugs of pregnancy complicated by rheumatic diseases, have increased significantly over the study interval. Conventional therapeutic drugs, especially glucocorticoids, LMWHs, and hydroxychloroquine were the most widely used drugs in pregnant patients with rheumatic diseases. However, IVIG and TNFi, relatively high cost, have shown gradual increases in clinical use since 2019.
Hippocampal region metabolites and cognitive impairment in patients with general paresis: based on 1H-proton magnetic resonance spectroscopy
Authors: Che Xin , Miao Tianyang , Shi Haishan , Li Zezhi , Ning Yuping 
Published: April 2024

Background:This study utilizes Hydrogen proton magnetic resonance spectroscopy (1H-MRS) to investigate metabolite concentrations in the bilateral hippocampus of general paresis (GP) patients.Methods:A total of 80 GP patients and 57 normal controls (NCs) were enrolled. Metabolite ratios in the bilateral hippocampus were measured using 1H-MRS. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on MMSE scores, participants were categorized into normal control, mild cognitive impairment, and moderate-severe dementia groups. Metabolite ratios (N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/choline (Cho), myoinositol (MI)/creatine (Cr), choline (Cho)/N-acetylaspartate (NAA)) were compared between groups, and correlations between metabolite ratios and cognitive performance were examined.Results:MMSE scores progressively decreased in the normal, mild cognitive impairment, and moderate-severe dementia groups (p &lt; 0.001). The moderate-severe dementia group showed significantly lower NAA/Cr ratios in the left hippocampus region (L-NAA/Cr ratios) (p &lt; 0.001) and higher Cho/NAA ratios in the left hippocampus region (L-Cho/NAA ratios) (p &lt; 0.05) compared to the other groups. However, differences in L-NAA/Cr and L-Cho/NAA ratios between the mild cognitive impairment group and the NC group were not significant in the hippocampus region (p &gt; 0.05). NAA/Cho and NAA/Cr ratios in the right hippocampus region (R-NAA/Cho and R-NAA/Cr ratios) in the moderate-severe dementia group were lower than those in the control group (p &lt; 0.05). No correlation was found between metabolite ratios and MMSE scores in bilateral hippocampus regions.Conclusion:There are distinctive metabolic characteristics in the hippocampus of GP patients. GP patients exhibited lower NAA/Cr and NAA/Cho ratios in the bilateral hippocampus, indicating neuron loss in these areas, which may become more pronounced as the disease progresses.
Acting out when psychosocial safety climate is low: understanding why middle-level managers experience upward mistreatment
Authors: Loh May Young , Dollard Maureen Frances 
Published: April 2024

IntroductionUpward mistreatment, despite being under studied, is an influential phenomenon affecting middle managers’ well-being and performance. The work environment hypothesis of bullying proposes that an undesirable work context is the main cause of workplace bullying, suggesting the importance of creating an anti-mistreatment climate, that is, psychosocial safety climate (PSC). In this study, we argue that upward bullying and aggression are unsafe behaviors, a “retaliation” by employees resulting from their unsafe work context.MethodsUsing a large-scale multisource sample collected from 123 organizations, 6,658 middle managers and 34,953 employees, we examined the relationship between collective PSC, individual-perceived PSC and middle managers’ experience of upward mistreatment.ResultsSingle-level and multi-level modeling results suggested that PSC is an important element in reducing the likelihood of upward bullying and aggression, in turn, protecting managers’ well-being. More importantly, upward bullying is a way that employees act out when there is an undesirable working context.DiscussionFuture research on workplace mistreatment should examine PSC and upward mistreatment. Interventions provided should focus on improving PSC which could in turn preventing upward mistreatment, thereby improving psychosocial safety for both employees and middle managers to prevent negative actions.