bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel variation in DEPDC5 causing familial focal epilepsy with variable foci
Authors: Wang Yanchi , Niu Wenbin , Shi Hao , Bao Xiao , Liu Yidong , Lu Manman , Sun Yingpu 
Published: June 2024

BackgroundDisheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families.MethodsA family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation.ResultsA novel variant, c.1217 + 2T&gt;A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5′ end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF.ConclusionThe results suggest that c.1217 + 2T&gt;A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.
CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp
Authors: Yang Hyun-Woo , Park Joo-Hoo , Shin Jae-Min , Son Hyeong-Guk , Kim Tae-Hoon , Lee Seung-Hoon , Park Il-Ho 
Published: June 2024

BackgroundChronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment.ObjectiveTo elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms.MethodsWe analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture.ResultsNasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations.ConclusionCHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.
Investigating Propionibacterium acnes antibiotic susceptibility and response to bacteriophage in vitro and in vivo
Authors: Yu Ruixing , Yu Lingyun , Ning Xiaoli , Cui Yong 
Published: June 2024

IntroductionA total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model.MethodsPatients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ2 test.ResultsThe results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model.DiscussionThis study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.
Longitudinal evaluation of laboratory results and method precision in worldwide erythropoietin external quality assessments
Authors: Toll Luisa , Weiss Nathalie , Vierbaum Laura , Schellenberg Ingo , Thevis Mario , Wenzel Folker 
Published: June 2024

Introduction: This study presents a longitudinal analysis of external quality assessment (EQA) results for erythropoietin (EPO) determinations conducted between 2017 and 2022 with a continuously increasing number of participating laboratories. The aim of this work was to evaluate participant performance and methodological aspects.Methods: In each of the eleven EQA surveys, a blinded sample set of lyophilized human serum containing one sample with lower EPO concentrations (L) and one with higher EPO concentrations (H) was sent to the participating laboratories.Results: A total of 1,256 measurements were included. The median (interquartile range) fraction of participants not meeting the criteria of acceptance set at 20% around the robust mean of the respective survey was 9.5% (6.1%–10.7%) (sample L) and 9.1% (5.8%–11.8%) (sample H) but lacked a clear trend in the observed period. Some surveys exhibited unusually high interlaboratory variation, suggesting interfering components in the EQA samples. Different immunological methods and reagent manufacturers also showed variability in measurement outcomes to some extent.Conclusion: These findings highlight the need for continuous quality assessment in EPO measurements to ensure patient safety and identify areas for further research and investigation.
Enhancing predictive validity of motoric cognitive risk syndrome for incident dementia and all-cause mortality with handgrip strength: insights from a prospective cohort study
Authors: Bai Weimin , Ma Ruizhu , Yang Yanhui , Xu Juan , Qin Lijie 
Published: June 2024

BackgroundThis study aimed to assess whether integrating handgrip strength (HGS) into the concept of motoric cognitive risk (MCR) would enhance its predictive validity for incident dementia and all-cause mortality.MethodsA cohort of 5, 899 adults from the Health and Retirement Study underwent assessments of gait speed, subjective cognitive complaints, and HGS were involved. Over a 10-year follow-up, biennial cognitive tests and mortality data were collected. Cox proportional hazard analyses assessed the predictive power of MCR alone and MCR plus HGS for incident dementia and all-cause mortality.ResultsPatients with MCR and impaired HGS (MCR-HGS) showed the highest adjusted hazard ratios (AHR) for dementia (2.33; 95% CI, 1.49–3.65) and mortality (1.52; 95% CI, 1.07–2.17). Even patients with MCR and normal HGS (MCR-non-HGS) experienced a 1.77-fold increased risk of incident dementia; however, this association was not significant when adjusted for socioeconomic status, lifestyle factors, and medical conditions. Nevertheless, all MCR groups demonstrated increased risks of all-cause mortality. The inclusion of HGS in the MCR models significantly improved predictive discrimination for both incident dementia and all-cause mortality, as indicated by improvements in the C-statistic, integrated discrimination improvement (IDI) and net reclassification indices (NRI).ConclusionOur study underscores the incremental predictive value of adding HGS to the MCR concept for estimating risks of adverse health outcomes among older adults. A modified MCR, incorporating HGS, could serve as an effective screening tool during national health examinations for identifying individuals at risk of dementia and mortality.
Effect of acupuncture on post-stroke dysphagia: a randomized controlled trial
Authors: Bai Lin , Cheng Hongliang , Hu Peijia , Wang Qingqing , Shilin Zhang , Shen Zhiqiang , Xu Fangyuan , Su Xingxing , Zhang Yiting 
Published: June 2024

IntroductionPost-stroke dysphagia (PSD) is associated with various complications that increase morbidity and mortality rates. Acupuncture has been used extensively in China to treat these complications; however, its therapeutic efficacy remains uncertain. We therefore aimed to study the clinical effects of acupuncture on PSD.MethodsPatients (n = 101) were randomly divided into acupuncture (n = 50) and rehabilitation training control (n = 51) groups based on the treatment used. Both groups were treated once daily, 6 days a week, for a total of 4 weeks. Pulse oxygen saturation (SpO2) and standardized swallowing assessment (SSA) were performed before the intervention, 2 weeks into treatment, after the intervention (4 weeks post-intervention), and at a 6-month follow-up (28 weeks). The levels of hemoglobin (Hb) and albumin (ALB), and 5-hydroxytryptamine (5-HT) and dopamine (DA) were measured before the intervention, 2 weeks into treatment, and after the intervention (4 weeks), as nutrition and swallowing function indices, respectively.ResultsFollowing the intervention, significant differences were observed between the acupuncture and control groups. The acupuncture group exhibited considerably superior enhancements in SpO2 and SSA scores at 4 weeks (p &lt; 0.001). Moreover, this group demonstrated significantly greater improvements in Hb, ALB, 5-HT, and DA values 4 weeks post-treatment (p &lt; 0.001). However, sex-based differences were not observed (P &gt; 0.005).ConclusionAcupuncture treatment can improve the swallowing function and nutritional status of patients with PSD, and increase the levels of 5-HT and DA. These findings strongly support the efficacy of acupuncture as a therapeutic intervention in patients with PSD.Clinicaltrial registration: identifier, ChiCTR2100052201. (https://www.chictr.org.cn/).
Bone mineral density and body composition in Australians following plant-based diets vs. regular meat diets
Authors: Austin Grace , Ferguson Jessica J. A. , Eslick Shaun , Oldmeadow Christopher , Wood Lisa G. , Garg Manohar L. 
Published: June 2024

Background and aimsBone mineral density (BMD) and body composition play an important role in maintaining metabolic health and physical functioning. Plant-based diets (PBDs) are known to be lower in protein and calcium, which can impact BMD and body composition. This study aimed to investigate the relationship between various PBDs compared to regular meat diet and whole-body BMD, body composition, and weight status.MethodsA cross-sectional study was conducted with adults (n = 240) aged 30–75 years, who habitually followed dietary patterns: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat eater (48 per group). Parameters were measured using dual-energy x-ray absorptiometry (DXA), and multivariable regression analyses were used to adjust for lifestyle confounders, socioeconomic factors, and BMI.ResultsAfter adjustments, whole-body BMD and body composition were not significantly different between those following PBDs and regular meat diets, except for lacto-ovo vegetarians, who had significantly lower lean mass by −1.46 kg (CI: −2.78, −0.13). Moreover, lacto-ovo vegetarians had a significantly lower T-score by −0.41 SD (CI: −0.81, −0.01) compared to regular meat eaters. Waist circumference was significantly lower in individuals adhering to a PBD compared to a regular meat diet: vegans by −4.67 cm (CI: −8.10, −1.24), lacto-ovo vegetarians by −3.92 cm (CI: −6.60, −1.23), pesco-vegetarians by −3.24 cm (CI: −6.09, −0.39), and semi-vegetarians by −5.18 cm (CI: −7.79, −2.57). There were no significant differences in lean mass (%), fat mass (% and total), android/gynoid measures, body weight, or BMI across dietary patterns. All dietary patterns met the recommended dietary intake for calcium and protein, and 25-hydroxy-vitamin D status was comparable across groups.ConclusionsThis cross-sectional study found that adhering to a PBD characterized by varying degrees of dairy and meat restriction is not associated with meaningful changes in BMD or body composition, provided that the dietary patterns are planned appropriately with adequate levels of calcium and protein.
Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study
Authors: Yang BoWen , Wang HanYu , Song WenYuan , Feng JiuHuan , Hou ShuFang 
Published: June 2024

BackgroundThe relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis.MethodsGenetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran’s Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk.ResultsIVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439–0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026–1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma.ConclusionsHMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.
Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis
Authors: McKinley Blake J. , Pai Tanmayi S. , Wolf Emily B. , Li Shenduo , Correia Guilherme Sacchi de Camargo , Zhao Yujie , Manochakian Rami , Lou Yanyan 
Published: June 2024

IntroductionLimited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs).MethodsWe conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis.ResultsA total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1–2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI.ConclusionsPatients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.
Modified Si Miao Powder granules alleviates osteoarthritis progression by regulating M1/M2 polarization of macrophage through NF-κB signaling pathway
Authors: He Qi , Tian Ding , Wang Zhiyuan , Zheng Dan , Zhi Liqiang , Ma Jianbing , An Jing , Zhang Rui 
Published: June 2024

BackgroundOsteoarthritis (OA) is a chronic degenerative disease mainly characterized by cartilage damage and synovial inflammation. Si Miao Powder, an herbal formula, was recorded in ancient Chinese medicine prescription with excellent anti-inflammatory properties. Based on the classical formula, the modified Si Miao Powder (MSMP) was developed with the addition of two commonly Chinese orthopedic herbs, which had the efficacy of strengthening the therapeutic effect for OA.MethodsIn the in vivo experiments, thirty-six 8-week-old male C57BL/6 mice were randomly divided into six groups: sham group, OA group, celecoxib group, low-MSMP group, middle-MSMP group, and high-MSMP group. OA mice were constructed by destabilization of medial meniscus (DMM) and treated with MSMP granules or celecoxib by gavage. The effects of MSMP on cartilage, synovitis and inflammatory factor of serum were tested. For in vitro experiments, control serum and MSMP-containing serum were prepared from twenty-five C57BL/6 mice. Macrophages (RAW264.7 cells) were induced by lipopolysaccharide (LPS) and then treated with MSMP-containing serum. The expression of inflammatory factors and the change of the NF-κB pathway were tested.ResultsIn vivo, celecoxib and MSMP alleviated OA progression in the treated groups compared with OA group. The damage was partly recovered in cartilage, the synovial inflammatory were reduced in synovium, and the concentrations of IL-6 and TNF-α were reduced and the expression of IL-10 was increased in serum. The function of the middle MSMP was most effective for OA treatment. The results of in vitro experiments showed that compared with the LPS group, the MSMP-containing serum significantly reduced the expression levels of pro-inflammatory (M1-type) factors, such as CD86, iNOS, TNF-α and IL-6, and promoted the expression levels of anti-inflammatory (M2-type) factors, such as Arg1 and IL-10. The MSMP-containing serum further inhibited NF-κB signaling pathway after LPS induction.ConclusionThe study demonstrated that MSMP alleviated OA progression in mice and MSMP-containing serum modulated macrophage M1/M2 phenotype by inhibiting the NF-κB signaling pathway. Our study provided experimental evidence and therapeutic targets of MSMP for OA treatment.
The relationship between physical activity and anxiety in college students: exploring the mediating role of lifestyle habits and dietary nutrition
Authors: Sun Dezhuo , Zhu Xiangfei , Bao Zhonghan 
Published: June 2024

BackgroundPhysical activity has been shown to be effective in treating and improving anxiety in college students. However, no studies have been conducted to examine the relationship between physical activity and anxiety in college students through mediating factors such as dietary nutrition and lifestyle habits. Therefore, the aim of this study was to examine the mediating role of lifestyle and dietary nutrition in the relationship between physical activity and anxiety.MethodsThis study used a stratified random sampling method to survey 498 college students from three universities in Fujian, China. Data on participants’ demographic characteristics, physical activity, lifestyle habits, and dietary nutrition were collected and analyzed using SPSS software. The proposed structural equation model was analyzed using Amos software.ResultsThe results of the study showed that dietary nutrition and lifestyle habits had significant independent mediating effects and continuous multiple mediating effects (p &lt; 0.01) in the effects of physical activity on college students’ anxiety. Dietary nutrition and lifestyle habits played an independent mediating role, accounting for 24.9% of the total effect; there was also a continuous multiple mediating effect between dietary nutrition and lifestyle habits, accounting for 13.27% of the total effect value. In addition, physical activity had a direct effect value on anxiety in college students, accounting for 36.93% of the total effect value.ConclusionBy increasing the behavior and awareness of college students to participate in physical activity, supplemented by guiding them to develop regular lifestyle habits and correct dietary nutritional patterns, the anxiety level of college students can be effectively improved and reduced. This type of regulation is an important reference for the self-management and rehabilitation of college students with anxiety disorders. Future studies can experimentally develop a combined intervention of physical activity, lifestyle habits, and dietary nutritional to help college students better cope with anxiety.