bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial low-affinity FcγR mediates the phagocytic elimination of dopaminergic neurons in Parkinson’s disease degeneration
Authors: Barcia Carlos , Casanova Paola , Saavedra-Lopez Elena , Freitag-Berenguel Irina , Usandizaga Maider , Martínez-Remedios Paula , Gimenez-Montes Claudia , Clinton Elsa , Roig-Martínez Meritxell , Cribaro George 
Published: October 2024

Abstract

Microglia-mediated neuroinflammation contributes to dopaminergic (DA) neurodegeneration in Parkinson’s disease (PD). It is thought that microglial cells interact with DA neurons of the substantia nigra pars compacta (SNpc), the most vulnerable region in parkinsonian neuropathology, playing a critical role through the process of neuronal loss. However, the specific mechanisms by which microglial reactivity is triggered and exerts such a deleterious effect remains unclear. Experimental models of PD in mice have shown that phagocytosis plays an essential role in the elimination of degenerating neurons, suggesting that blocking this microglial function could be beneficial to preserve remaining DA neurons. In the present work, we pinpoint the role of the Fcγ receptor (FcγR) as a potential trigger of microglial phagocytosis in PD. We found that the FcγR is overexpressed in the degenerating SNpc in postmortem samples of PD patients, alongside histological indications of phagocytic microglia. Likewise, experimental models of PD also show increased FcγR expression, together with evidence of similar phagocytosis events. Most importantly, blocking FcγR in vitro, by using neutralizing antibodies, reduced the microglial-mediated elimination of DA cells. High resolution imaging revealed that the FcγR is involved in phagocytic synapse formation, and appeared polarized, and segregated to actin-rich protruding cups, when interacting one-on-one towards single target DA cells. Additionally, by inhibiting FcγR downstream actin-polymerizing signaling Cdc42, microglia were unable to eliminate DA cells. Finally, experiments in vivo, using an experimental model of PD in mouse, revealed that passive immunotherapy with FcγR neutralizing monoclonal antibodies, as well as inhibiting its downstream signaling Cdc42, protect DA neurons from elimination. These results indicate that the FcγR may be a critical factor inducing DA neuron phagocytosis in PD and suggest a novel immunotherapeutic strategy targeting microglia to preserve neuronal loss.
The role of ALK gene and PI3k/Akt/NF - κ B signaling pathway in precancerous lesions of cervical cancer
Authors: Qi Ding , Sun Yiming , Ai Wenxia , Han Buwei , Liang Mingge , Zhang Mingshu , Xia Yonggang , Liu Li 
Published: October 2024

Abstract

The study aimed to unravel the molecular basis of cervical precancerous lesions leveraging bioinformatic tools to pinpoint crucial genes and signaling cascades. A multi-faceted approach was undertaken, commencing with GEO database mining for differential gene expression between CSILs and healthy cervical tissues. STRING 11.0 facilitated protein-protein interaction (PPI) analysis, generating a network visualized in Cytoscape 3.7.2. Gene Ontology (GO) and KEGG pathway enrichment via DAVID illuminated biological functions and pathways associated with identified differentially expressed genes (DEGs). GSEA further refined key genes and enriched modules. Concurrently, qRT-PCR validation on cervical biopsy samples from eligible patients corroborated bioinformatic findings. The analysis pinpointed 371 common DEGs across datasets, leading to the discovery of 102 biological processes, 33 cellular components, 15 molecular functions, 29 significant pathways, and 3 pivotal genes. Clinical assessment linked lesion severity to age, vaginal microbiota characteristics, and ALK gene/PI3K/AKT/NF-κB pathway activity. qRT-PCR verified heightened ALK and PI3K/AKT/NF-κB signaling in high-grade lesions, underscoring their roles in CSIL pathogenesis. The importance of this research lies in its potential to inform the development of targeted therapies and personalized treatment strategies for cervical precancerous lesions. By identifying the molecular drivers of the disease, researchers can design interventions that precisely target these pathways, improving patient outcomes and reducing the burden of cervical cancer.
M6A and lactylation modification-related signature predicts prognosis and immunotherapy response in hepatocellular carcinoma
Authors: Ren Huili , Liu Jianhua , Zhang Shaohui 
Published: October 2024

Abstract

This study aims to investigate the role of lactylation and m6A modification-related genes in the tumor microenvironment and immunotherapy for hepatocellular carcinoma (HCC) patients. RNA-sequence data and corresponding clinical information of HCC were obtained from the TCGA and ICGC datasets. LASSO Cox regression analysis was implied to construct a lactylation-m6A related prognostic model. The 7-gene signature was established and effectively stratified patients into high- and low-risk groups. Further analysis revealed significant differences between the two risk groups in terms of tumor microenvironment, expression levels of immune checkpoint genes, and drug responsiveness. Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. Functionally, knockdown of TCOF1 and HDAC1 significantly attenuated the migration and invasive capacity of Huh-7 liver cancer cells. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results.
An exploration of the correlation between strain energy density in the temporomandibular joint and facial morphologic parameters
Authors: Murakami Kazuhiro , Kawakami Masayoshi , Yamamoto Kazuhiko , Horita Satoshi 
Published: October 2024

Abstract

Purpose: The purpose of this was to construct finite element (FE) models based on computed tomography (CT) data of individual patients during orthodontic treatment and to evaluate the relationship between strain energy density (SED) in the temporomandibular joint (TMJ) disc and the facial morphology of three skeletal patterns (Class 1–3) by cephalometric analysis.
Methods: Cephalometric analyses were performed on 53 patients. FE models based on the CT images of each patient were constructed, and the mean SED in the bilateral TMJ disc was calculated. The relationships between SED and the cephalometric parameters were evaluated.
Results: SED was significantly greater in Classes 1 and 2 than in Class 3 (p < 0.05). A positive correlation was observed between SED and the parameter of, convexity and ANB angle (p < 0.01), whereas a negative correlation was observed between SED and facial angle in Class 3(p < 0.05). A positive correlation was identified between SED and gonial angle in Class 1(p < 0.05). In all cases, correlations were observed between SED and facial angle (p < 0.05), convexity(p < 0.01), mandibular angle(p < 0.05), Y-axis(p < 0.05), SNB (p < 0.05), ANB angle(p < 0.01), and overjet(p < 0.05).
Conclusion: An increase in SED in the TMJ disc was observed when the mandible was rotated clockwise and positioned superior posteriorly. Furthermore, SED was affected by an overjet of dental parameters. Numerically, the present study suggests that SED generated in the TMJ disc was primarily affected by mandibular morphology. Considering that an increase in SED causes damage to the articular disc, three skeletal parameters (facial angle, convexity, and ANB) are useful in predicting TMJ dysfunction.
The Role of Dietary Vitamin E in Preventing Degenerative Musculoskeletal Diseases: Insights from Mendelian Randomization
Authors: jiewen Wei 
Published: October 2024

Abstract

Background
Degenerative musculoskeletal diseases, including osteoarthritis, osteoporosis, intervertebral disc degeneration, and sarcopenia, significantly impair patient mobility and quality of life, particularly in the elderly. Despite extensive research, the pathogenesis of these diseases remains incompletely understood, and effective treatments are lacking. Recent evidence suggests that oxidative stress and inflammation play crucial roles in the development of these conditions. Vitamin E, a potent antioxidant, has been proposed as a potential protective factor.
Objective
To investigate the causal relationship between dietary vitamin E intake and the risk of degenerative musculoskeletal diseases using a two-sample Mendelian randomization (MR) approach.
Methods
I utilized data from the UK Biobank's IEU OpenGWAS, the Finnish FinnGen Biobank, and the PhenoScanner database. Genetic variants associated with vitamin E intake were used as instrumental variables. Outcome data for OA, OP, SP, and IVDD were obtained from large-scale genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was the primary analysis, supported by MR-Egger, weighted median, and other sensitivity analyses to ensure robustness.
Results
The IVW method revealed no significant causal association between vitamin E intake and the risk of OA, OP, SP, or IVDD. Sensitivity analyses, including Cochran’s Q test and the MR-Egger intercept test, indicated no evidence of heterogeneity or horizontal pleiotropy. Leave-one-out analyses confirmed that no single SNP significantly influenced the overall causal effect estimates.
Conclusion
This MR study found no evidence to support a causal relationship between dietary vitamin E intake and the risk of degenerative musculoskeletal diseases. These findings suggest that vitamin E supplementation may not be effective in preventing or managing these conditions. Future research should explore other potential factors and consider different populations to further understand the role of vitamin E in musculoskeletal health.
Utility of simplified echocardiographic criteria for diagnosing subclinical rheumatic heart disease among primary and secondary school scholars in Kondoa District, Dodoma, Tanzania: A cross-sectional study
Authors: Macha Edgar , Baraka Alphonce , Karoli Peter , Kagaruki Gibson , Mayige Mary , Mutagaywa Reuben , Meda John 
Published: October 2024

Abstract

Background: Rheumatic heart disease is among the major causesof morbidity and mortality among children and young adults in low-income countries. Early detection of subclinical rheumatic heart disease and initiation of secondary prophylaxis prevents progression into clinical rheumatic heart disease. In 2012, the World Heart Federation established criteria for the diagnosis of subclinical rheumatic heart disease. However, the applicability and feasibility of screening in low-income settings with insufficient resources has been a setback. The aimof thisstudy was to validate simplified echocardiographic criteria for the diagnosis ofsubclinical rheumatic heart disease.
Methods: A school-based cross-sectional study was conducted among primary and secondary school scholars between the ages of 5 and 20 years in Kondoa District. Eligible primary and secondary school scholars underwent two echocardiographic screens on the basis of simplified echocardiographic criteria by non-expert personnel and then the World Heart Federation criteria of 2012 by expert personnel. Continuous variables are presented as the means with standard deviations or medians with IQRs. Categorical variables are presented as frequencies and percentages. Echocardiographic findings by simplified criteria were compared to the findings of the World Heart Federation 2012. Using cross tabulation in STATA, the utility of the simplified criteria was determined. The two criteria were assessed and compared via the area under the receiver operating characteristic curve (AUC) with a 95% CI.
Results: Of the 2175 participants sampled, only 1618 underwent echocardiographic screening. The prevalence of subclinical RHD was 14 per 1000. Among the 22 children with subclinical rheumatic heart disease, 14 had definite disease, whereas 8 had borderline rheumatic heart disease. The sensitivity, specificity, positive predictive value and negative predictive value of the simplified criteria for the diagnosis of SHCD were 100% (95% CI 100–100%), 99.69% (95% CI 99.41–99.96%), 81.48% (95% CI 79.59–83.37%), and 100% (95% CI 100–100%), respectively. The area under the curve (AUC) for the simplified criteria for diagnosing subclinical RHD was 0.998 (95% CI 0.997–1.000, p < 0.001).
Conclusion: In resource-limited endemic areas with a lack of expert personnel, simplified echocardiographic criteria are useful screening tools for the diagnosis of subclinical Rheumatic Heart Disease.
Transvaginal Repair of Apical Vesicovaginal Fistula via Vaginal Natural Orifice Transluminal Endoscopic Surgery (V-NOTES): A Modified Surgical Technique and Its Outcomes
Authors: Song Xin , Jiang Chen , Lv Jian-wei 
Published: October 2024

Abstract

Objective
To report the procedure of an alternative modified transvaginal repair technique (V-NOTES) and their outcomes in apical vesicovaginal fistula.
Methods
Between January 2020 and January 2023, gynecological procedures resulted in the diagnosis of apical VVFs in 26 patients, 17 of whom had undergone transvaginal repair of apical vesicovaginal fistula via vaginal V-NOTES. Those patients were contacted and followed up. Outcomes included operative time, blood loss, success rate, postoperative hospital stay.
Results
The average age of the patients was 45.82(36–53) yr. The mean duration between onset of fistula and repair was 7.18(3–12) mo. The mean estimated blood loss was 10.45 ± 3.23ml, and the average operative time was 104.2 ± 12.2min. Patients’ postoperative hospital stay was 3.34 ± 0.72 days on average. The VVF was successfully repaired in 15(88.2%) cases, and failure was observed in 2 patients. All the 2 initial failures were cured in the second repair. No major complications developed in all 17 patients. There were also no fever (> 38℃), urge incontinence or infection in incision area.
Conclusions
Our study suggest that the transvaginal repair of apical VVF via V-NOTES is effective and safety, and offers anticipated results without obvious complications.
Repetitive transcranial magnetic stimulatation alleviates motor impairment in Parkinson's disease: association with peripheral inflammatory regulatory T-cells and SYT6
Authors: Xie Fen , Shen BIbiao , Luo Yuqi , Zhou Hang , Xie Zhenchao , Zhu Shuzhen , Wei Xiaobo , Chang Zihan , Zhu Zhaohua , Ding Changhai , Jin Kunlin , Yang Chengwu , Batzu Lucia , Chaudhuri K Ray , Chan Ling-Ling , Tan Eng-King , Wang Qing 
Published: October 2024

Abstract

Background
Repetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying the therapeutic effect of rTMS on Parkinson’s disease (PD) has not been fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears to be a key modulator of disease progression in PD. If rTMS affects the peripheral Tregs in PD remains unknown.
Methods
Here, we conducted a prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 PD patients who received 10-day rTMS (10 Hz) stimulation on the primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well as flow cytology study were undertaken in 54 PD patients who were consecutively recruited from the department of neurology at Zhujiang hospital between September 2021 and January 2022. Subsequently, we implemented flow cytometry analysis to examine the Tregs population in spleen of MPTP-induced PD mice that received rTMS or sham treatment, along with quantitative proteomic approach reveal novel molecular targets for Parkinson's disease, and finally, the RNA interference method verifies the role of these new molecular targets in the treatment of PD.
Results
We demonstrated that a 10-day rTMS treatment on the M1 motor cortex significantly improved motor dysfunction in PD patients. The beneficial effects persisted for up to 40 days, and were associated with an increase in peripheral Tregs. There was a positive correlation between Tregs and motor improvements in PD cases. Similarly, a 10-day rTMS treatment on the brains of MPTP-induced PD mice significantly ameliorated motor symptoms. rTMS reversed the downregulation of circulating Tregs and tyrosine hydroxylase neurons in these mice. It also increased anti-inflammatory mediators, deactivated microglia, and decreased inflammatory cytokines. These effects were blocked by administration of a Treg inhibitor anti-CD25 antibody in MPTP-induced PD mice. Quantitative proteomic analysis identified TLR4, TH, Slc6a3 and especially Syt6 as the hub node proteins related to Tregs and rTMS therapy. Lastly, we validated the role of Treg and rTMS-related protein syt6 in MPTP mice using the virus interference method.
Conclusions
Our clinical and experimental studies suggest that rTMS improves motor function by modulating the function of Tregs and suppressing toxic neuroinflammation. Hub node proteins (especially Syt6) may be potential therapeutic targets.
Trial registration: Chinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691
The Role of Immune Cells in Colorectal Cancer: A Mendelian Randomization Study and Validation in A Single-Center Case-Control Trial.
Authors: Sun Luan-Biao , Zhou XuanPeng , Song Xin-Yuan , Xing Jian-Peng , Gao Shuo-Hui 
Published: October 2024

Abstract

Background: Although a growing body of research suggests that alterations in the composition of the immune system play a critical role in the development of colorectal cancer (CRC), the causal and prognostic relationship between specific immune cells and the risk of CRC development remains unclear.
Method: In this study, Mendelian randomization (MR) was employed to investigate the causal relationship between immunophenotypes and colorectal cancer. To explore the potential associations, five MR methods were applied: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, Weighted Mode, and Simple mode. If the results of the five methods are inconclusive, we favored the IVW as the primary outcome. In addition, heterogeneity and pleiotropy were tested using MR-Egger, MR-PRESSO-Global, and Cochrane's Q. Stability of MR findings was assessed using leave-one-out approach, and the strength of the causal relationship between exposure and outcome was tested using the Bonferroni correction. Additional single-center clinical case-control samples were utilized to validate the results of Mendelian randomization, and prognostic results were visualized by logistic regression models, COX regression models, and Kaplan-Meier survival curves.
Result: Among 731 immunophenotypes were tested, 26 immunophenotypes were associated with CRC risk. The Bonferroni-corrected testing reveals that Lymphocyte %leukocyte and CD3 on CM CD8br had a significant causal association with CRC. According to Cochrane's Q test, there was no significant heterogeneity across different single-nucleotide polymorphisms. Furthermore, the MR-Egger and MR-PRESSO-Global tests did not show pleiotropy. There was no reverse causality between the CRC risk and immunophenotypes. In the single-center clinical case-control study demonstrated a positive causal relationship between the relative counts of lymphocytes and CD4+T cells and the risk of CRC development. Furthermore, our correlation analysis also demonstrated a potential association between lymphocyte relative counts and poor prognosis in CRC cases.
Conclusion: Through MR analysis, we established a causal relationship between lymphocytes and maturation stages of T cell in the risk of CRC development. Additionally, case-control studies focusing on circulating lymphocytes and their subpopulations have further validated that these cells are integral to both the pathogenesis and prognosis of CRC. This finding may provide valuable ideas for early, noninvasive detection and potential immunotherapeutic targets for CRC.
‘Technology Alone Is Not Enough: The Role of Operational Efficiency in Bridging AI and Patient Outcomes’ – Insights from Taiwanese Healthcare Facilities"
Authors: Hung-Xin Li 
Published: October 2024

Abstract

This research investigates the equitable distribution of healthcare resources and its impact on patient outcomes, along with the relationship between resource allocation strategies and operational efficiency in Taiwan's healthcare system. Using a mixed-methods approach, the study explores these strategies through qualitative data from semi-structured interviews analyzed with NVIVO software and quantitative data collected via surveys from hospital administrators, safety teams, and financial personnel. A sequential random sampling method selected healthcare institutions based on size, location, and specialty services. The findings reveal a strong correlation between the adoption of AI techniques, healthcare quality, patient care service utilization, and improved patient outcomes, although resource allocation alone does not directly affect patient outcomes. Operational efficiency plays a mediating role, contributing to better patient results. The study emphasizes the need for integrating efficient resource management and operational practices to enhance patient outcomes, providing actionable insights for healthcare administrators to improve care quality and accessibility. It also highlights the importance of developing tailored resource management strategies that consider regional and organizational differences within Taiwan’s healthcare system.
Prognostic Value of Baseline Skeletal Muscle Index in Colorectal Cancer Patients Treated with Fruquintinib：A multi-center real world analysis
Authors: Tang Wanfen , Li Fakai , Zheng Hongjuan , Zhao Jinglei , Wei Hangping , Xiong Xuerong , Chen Hailang , Zhang Cui , Xie Weili , Zhang Penghai , Gong Guangrong , Ying Mingliang , Guo Qiusheng , Wang Qinghua , Fu Jianfei 
Published: October 2024

Abstract

Background
The Skeletal Muscle Index (SMI) is an objective indicator for evaluating the nutritional status in malignant tumors. The baseline nutritional status may affect the efficacy and prognosis of targeted anti-tumor therapy, and growth factor tyrosine kinase inhibitors often lead to drug-related sarcopenia. Fruquintinib has been approved for metastatic colorectal cancer. In this study, we analyzed the prognostic value of baseline SMI in metastatic colorectal cancer treated with fruquintinib, and observed the incidence of SMI reduction after fruquintinib treatment to evaluate its impact on prognosis.
Methods
A retrospective multi-center analysis of metastatic colorectal cancer patients treated with fruquintinib in eight medical centers in China was performed. The muscle area of the third lumbar spine was evaluated, the baseline SMI and post-treatment SMI were calculated separately. The correlation with survival was analyzed.
Results
The median PFS of 105 patients was 4.2 months (95% CI, 3.7 months to 4.9 months), and the median OS was 10.2 months (95% CI, 9.0 months to 12.7 months). The baseline SMI before fruquintinib therapy was significantly correlated with OS (P = 0.0077). Multivariate analysis demonstrated that the baseline SMI was an independent prognostic factor for OS (P = 0.005). Twenty-eight point eight seven percent (28.87%) patients experienced sarcopenia after oral administration of fruquintinib. However, there was no significant difference in OS between the SMI reduced group and the SMI nonreduced group after treatment with fruquintinib.
Conclusion
The baseline SMI was an independent prognostic factor for OS and it could affect the survival of patients treated with fruquintinib in metastatic colorectal cancer. Although fruquintinib can cause sarcopenia, there is no correlation between post-treatment SMI changes and survival.