bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary magnesium and calcium intake is associated with lower risk of hearing loss in older adults: A cross-sectional study of NHANES
Authors: Wei Xinmin 
Published: March 2023

AimDietary intake as a modifiable factor has been reported to be associated with hearing loss (HL). The relationship between magnesium (Mg) and calcium (Ca) as common dietary nutrients and HL in the elderly has rarely been reported. This study aimed to assess the association between Mg and Ca intake and HL in older adults.MethodThis cross-sectional study included participants aged ≥70 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2009–2010, and 2017–2018. Outcomes were low-frequency [pure-tone averages (PTAs) at 500, 1000, and 2000 Hz &gt;25 dB] and speech-frequency (PTAs at 500, 1000, 2000, and 4,000 Hz &gt;25 dB) HL. Multivariate logistic analysis was utilized to explore the association between dietary Mg and Ca intake and their combined intake (Ca/Mg, Ca*Mg) and HL, and was described as odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 1,858 participants were included, of which 1,052 (55.95%) had low-frequency HL and 1,349 (72.62%) had speech-frequency HL. Dietary Ca intakes [OR = 0.86, 95%CI: (0.74–0.99)] and Mg intakes [OR = 0.81, 95%CI: (0.68–0.95)] and Ca * Mg [OR = 0.12, 95%CI: (0.02–0.87)] were associated with lower odds of low-frequency HL after adjusting for confounders. Similar, dietary Ca intakes [OR = 0.85, 95%CI: (0.77–0.95)] and Mg intakes [OR = 0.78, 95%CI: (0.68–0.90)] and Ca * Mg [OR = 0.23, 95%CI: (0.05–0.78)] were related to lower odds of speech-frequency HL. For different levels of Mg and Ca intake, the combined intake of Ca (≥1,044 mg) and Mg (≥330 mg) was related to lower odds of low-frequency HL [OR = 0.02, 95%CI: (0.00–0.27)] and speech-frequency HL [OR = 0.44, 95%CI: (0.21–0.89)].ConclusionDietary intakes of Mg and Ca were associated with lower odds of HL and are a promising intervention to be further explored in older adults with HL.
Role of prebiotic dietary fiber in periodontal disease: A systematic review of animal studies
Authors: Tailor Rohan , Medara Nidhi , Chopra Aditi , Swarnamali Hasinthi , Eberhard Joerg , Jayasinghe Thilini N. 
Published: March 2023

BackgroundPeriodontitis is a chronic inflammatory condition affecting the supporting structures of a tooth in the oral cavity. The relationship between dietary fiber and periodontitis is poorly understood. The objective of this systematic review is to investigate if an intake of dietary fiber modulates periodontal disease in animal models and any concomitant effects on systemic inflammation, microbiota and their metabolites.MethodsAnimal studies using periodontitis models with any form of fiber intervention were included. Studies with comorbidities that were mutually inclusive with periodontitis and animals with physiological conditions were excluded. Search strategy with MeSH and free-text search terms were finalized and performed on the 22nd of September 2021.CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus® and Web of Science Core Collection databases were used to identify studies. SYRCLE’s risk of bias tool and CAMARADES were used for quality assessment. Results were synthesized utilizing Covidence© web-based platform software to remove duplicates, and the remaining studies were manually filtered.ResultsA total of 7,141 articles were retrieved from all databases. Out of 24 full-text articles assessed for eligibility, four studies (n = 4) were included. Four studies involved the use of β-(1,3/1,6)-glucan (n = 3) and mannan oligosaccharide (n = 1) at differing dosages for different study durations. All studies utilized a ligature-induced model of periodontitis in rats, either Wistar (n = 3) or Sprague–Dawley (n = 1). A dose-dependent relationship between the increased fiber intake and decrease in alveolar bone loss and pro-inflammatory markers was observed.ConclusionThe number of included studies is limited and narrow in scope. They highlight the importance of pre-clinical trials in this field with broader dietary fiber intervention groups before proceeding to clinical trials. The use of dietary fiber as an intervention shows promise in the reduction of inflammatory conditions like periodontitis. However, further research is required to delineate the relationship between diet and its effects on microbiota and their metabolites such as short chain fatty acids in animal models of periodontitis.
Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer
Authors: Yang Guo , Chen Xiong , Quan Zhen , Liu Miao , Guo Yuan , Tang Yangbin , Peng Lang , Wang Leilei , Wu Yingying , Wu Xiaohou , Liu Jiayu , Zheng Yongbo 
Published: March 2023

BackgroundProstate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa.MethodsRNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1low and FOXA1high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa.ResultsA ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients’ blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells.ConclusionsOur findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.
The polymorphisms of ANXA6 influence head and neck cancer susceptibility in the Chinese Han population
Authors: Xiong Weihong , Li Zhumei , Zeng Xiangfa , Cui Jun , Cheng Zhiming , Yang Xiaoying , Ding Yipeng 
Published: March 2023

BackgroundHead and neck cancer (HNC) is the sixth most common malignant tumor worldwide and imposes a serious economic burden on society and individuals. Annexin has been implicated in multiple functions which are essential in HNC development, including cell proliferation, apoptosis, metastasis, and invasion. This study focused on the linkage between ANXA6 variants and HNC susceptibility in Chinese people.MethodsEight SNPs in ANXA6 from 139 HNC patients and 135 healthy controls were genotyped by the Agena MassARRAY platform. The correlation of SNPs with HNC susceptibility was evaluated using odds ratio and 95% confidence interval calculated by logistic regression using PLINK 1.9.ResultsOverall analysis results demonstrated that rs4958897 was correlated with an increased HNC risk (allele: OR = 1.41, p = 0.049; dominant: OR = 1.69, p = 0.039), while rs11960458 was correlated with reduced HNC risk (OR = 0.54, p = 0.030). In age ≤ 53, rs4958897 was related to reduce HNC risk. In males, rs11960458 (OR = 0.50, p = 0.040) and rs13185706 (OR = 0.48, p = 0.043) were protective factors for HNC, but rs4346760 was a risk factor for HNC. Moreover, rs4346760, rs4958897, and rs3762993 were also correlated with increased nasopharyngeal carcinoma risk.ConclusionsOur findings suggest that ANXA6 polymorphisms are linked to the susceptibility to HNC in the Chinese Han population, indicating that ANXA6 may serve as a potential biomarker for HNC prognosis and diagnosis.
The role of EphA2 in ADAM17- and ionizing radiation-enhanced lung cancer cell migration
Authors: Waller Verena , Tschanz Fabienne , Winkler Rona , Pruschy Martin 
Published: March 2023

PurposeIonizing radiation (IR) enhances the migratory capacity of cancer cells. Here we investigate in non-small-cell-lung-cancer (NSCLC) cells a novel link between IR-enhanced ADAM17 activity and the non-canonical pathway of EphA2 in the cellular stress response to irradiation.MethodsCancer cell migration in dependence of IR, EphA2, and paracrine signaling mediated by ADAM17 was determined using transwell migration assays. Changes of EphA2 pS897 and mRNA expression levels upon different ADAM17-directed treatment strategies, including the small molecular inhibitor TMI-005, the monoclonal antibody MEDI3622, and shRNAs, were mechanistically investigated. ADAM17-mediated release and cleavage of the EphA2 ligand ephrin-A1 was measured using ELISA and an acellular cleavage assay.ResultsIrradiation with 5 Gy enhanced tumor cell migration of NSCLC NCI-H358 cells in dependence of EphA2. At the same time, IR increased growth factor-induced EphA2 S897 phosphorylation via auto- and paracrine signaling. Genetic and pharmaceutical downregulation of ADAM17 activity abrogated growth factor (e.g. amphiregulin) release, which reduced MAPK pathway-mediated EphA2 S897 phosphorylation in an auto- and paracrine way (non-canonical EphA2-pathway) in NCI-H358 and A549 cells. These signaling processes were associated with reduced cell migration towards conditioned media derived from ADAM17-deficient cells. Interestingly, ADAM17 inhibition with the small molecular inhibitor TMI-005 led to the internalization and proteasomal degradation of EphA2, which was rescued by amphiregulin or MG-132 treatment. In addition, ADAM17 inhibition also abrogated ephrin-A1 cleavage and thereby interfered with the canonical EphA2-pathway.ConclusionWe identified ADAM17 and the receptor tyrosine kinase EphA2 as two important drivers for (IR-) induced NSCLC cell migration and described a unique interrelation between ADAM17 and EphA2. We demonstrated that ADAM17 influences both, EphA2 (pS897) and its GPI-anchored ligand ephrin-A1. Using different cellular and molecular readouts, we generated a comprehensive picture of how ADAM17 and IR influence the EphA2 canonical and non-canonical pathway in NSCLC cells.
A novel immune-related model to predict prognosis and responsiveness to checkpoint and angiogenesis blockade therapy in advanced renal cancer
Authors: Chen Peng , Bi Feng , Tan Weili , Jian Lian , Yu Xiaoping 
Published: March 2023

BackgroundImmune checkpoint blockade (ICB) and anti-angiogenic drug combination has prolonged the survival of patients with advanced renal cell carcinoma (RCC). However, not all patients receive clinical benefits from this intervention. In this study, we aimed to establish a promising immune-related prognostic model to stratify the patients responding to ICB and anti-angiogenic drug combination and facilitate the development of personalized therapies for patients with RCC.Materials and methodsBased on clinical annotations and RNA-sequencing (RNA-seq) data of 407 patients with advanced RCC from the IMmotion151 cohort, nine immune-associated differentially expressed genes (DEGs) between responders and non-responders to atezolizumab (anti-programmed death-ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor antibody) treatment were identified via weighted gene co-expression network analysis. We also conducted single-sample gene set enrichment analysis to develop a novel immune-related risk score (IRS) model and further estimate the prognosis of patients with RCC by predicting their sensitivity to chemotherapy and responsiveness to immunotherapy. IRS model was further validated using the JAVELIN Renal 101 cohort, the E-MTAB-3218 cohort, the IMvigor210 and GSE78220 cohort. Predictive significance of the IRS model for advanced RCC was assessed using receiver operating characteristic curves.ResultsThe IRS model was constructed using nine immune-associated DEGs: SPINK5, SEMA3E, ROBO2, BMP5, ORM1, CRP, CTSE, PMCH and CCL3L1. Advanced RCC patients with high IRS had a high risk of undesirable clinical outcomes (hazard ratio = 1.91; 95% confidence interval = 1.43–2.55; P &lt; 0.0001). Transcriptome analysis revealed that the IRS-low group exhibited significantly high expression levels of CD8+ T effectors, antigen-processing machinery, and immune checkpoints, whereas the epithelial–mesenchymal transition pathway was enriched in the IRS-high group. IRS model effectively differentiated the responders from non-responders to ICB combined with angiogenesis blockade therapy or immunotherapy alone, with area under the curve values of 0.822 in the IMmotion151 cohort, 0.751 in the JAVELIN Renal 101 cohort, and 0.776 in the E-MTAB-3218 cohort.ConclusionIRS model is a reliable and robust immune signature that can be used for patient selection to optimize the efficacy of ICB plus anti-angiogenic drug therapies in patients with advanced RCC.
The cholesterol-lowering effect of statins is modified by LILRB5 intolerance genotype: Results from a recruit-by-genotype clinical trial
Authors: Tornio Aleksi , Bigossi Margherita , Siddiqui Moneeza K. , Kennedy Gwen , Melhem Ala’a , Chourasia Mehul K. , Maroteau Cyrielle , Pola Roberto , Chasman Daniel I. , Doney Alexander S. F. , Palmer Colin N. A. 
Published: March 2023

Background/Aims: Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The LILRB5 Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets.Methods: A double-blind, cross-over, recruit-by-genotype trial was undertaken. A total of 18 participants who had either the Asp247Asp (T/T) genotype or the Gly247Gly (C/C) genotype were recruited to the study. Participants were randomised to receive placebo or atorvastatin 80 mg daily for 28 days. Following a washout period of 3 weeks, they were then switched to the opposite treatment. Biochemical and immunological measurements as well as interviews were performed prior to and after both treatment periods. Within genotype group comparisons were performed using repeated measures Wilcoxon tests. Two-way repeated measures ANOVA with genotype and treatment as factors were used to compare changes in biochemical parameters between groups during placebo and atorvastatin periods.Results: Individuals with the Asp247Asp genotype had a greater increase in creatine kinase (CK) compared to those with Gly247Gly genotype in response to atorvastatin (p = 0.03). Those with Gly247Gly genotype had a mean non-HDL cholesterol reduction of 2.44 (95% CI:1.59 – 3.29) mmol/L while in Asp247Asp genotype group the mean reduction was 1.28 (95%CI: 0.48 – 2.07) mmol/L. The interaction between the genotype and atorvastatin treatment for total cholesterol (p = 0.007) and non-HDL cholesterol response was significant (p = 0.025). Immunological assessment showed no significant changes in aggregation of T regulatory cells by genotype.Conclusion: The Asp247Gly variant in LILRB5, previously associated with statin intolerance, was associated with differential increases in creatine kinase and total cholesterol and non-HDL cholesterol-lowering response to atorvastatin. Taken together, these results suggest that this variant could have utility in precision cardiovascular therapy.
Efficacy of Perilla frutescens (L.) Britton var. frutescens extract on mild knee joint pain: A randomized controlled trial
Authors: Kim NamHoon , Kim Si-Yeon , Kim Sang-Woo , Lee Jung Min , Kim Sung-Kyu , Park Mi-Houn , Kim Ki-Hwan , Oh Minseok , Son Chang-Gue , Jung In Chul , Lee Eun-Jung 
Published: March 2023

Objectives: This study aimed to evaluate the clinical efficacy and safety of PE extracts developed for the purpose of relieving pain and improving knee joint function on semi-healthy people with mild knee joint pain.Methods: A randomized, double-blind, two-arm, single-center, placebo-controlled clinical trial was conducted. Individuals with knee joint pain and a visual analogue scale (VAS) score &lt; 50 mm were included in the study, and participants with radiological arthritis were excluded. Participants were administered either PFE or a placebo capsule (700 mg, twice a day) orally for eight weeks. The comparisons of the changed VAS score and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores between the PFE and placebo groups were primary outcomes, while the five inflammation-related laboratory tests including cartilage oligomeric matrix protein, cyclooxygenase-2, neutrophil and lymphocyte ratio, high sensitive C-reactive protein, and erythrocyte sedimentation rate were secondary outcomes. Also, a safety assessment was done.Results: Eighty participants (mean age, 38.4 ± 14.0, male: female, 28:52) were enrolled; 75 completed the trial (PFE 36 and placebo 39). After eight weeks, both VAS and WOMAC scores were reduced in the PFE and placebo groups. The changed scores were significantly higher in the PFE group compared to the placebo group: 19.6 ± 10.9 vs. 6.8 ± 10.5; VAS scores (p &lt; 0.001), and 20.5 ± 14.7 vs. 9.3 ± 16.5; total WOMAC scores (p &lt; 0.01) including the sub-scores for pain, stiffness, and functions. No significant changes were reported in the five inflammation-related laboratory parameters. All adverse events were considered minor and unlikely to result from the intervention.Conclusion: Eight weeks of PFE intake was more effective than placebo in reducing knee joint pain and improving knee joint function in sub-healthy people with mild knee joint pain, and there were no major safety concerns.Clinical Trial Registration:https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&amp;focus=reset_12&amp;search_page=M&amp;pageSize=10&amp;page=undefined&amp;seq=23101&amp;status=5&amp;seq_group=19745, identifier CRIS: KCT0007219
Yiqi Huazhuo decoction increases insulin secretion in type 2 diabetic rats by regulating the pancreatic GPR40-IP3R-1 signaling pathway
Authors: Wu Dongjiao , Weng Siying , Xu Shuyi , Li Yan , Zhou Jianyang 
Published: March 2023

Objective: Yiqi Huazhuo Decoction (YD) reduces blood glucose, glycated hemoglobin, body weight, and insulin resistance in patients with type 2 diabetes mellitus (T2DM), but its exact mechanisms are unknown. This study investigated the therapeutic effects and mechanisms of YD on impaired insulin secretion in T2DM rats.Methods: T2DM rats were randomized to the model, YD-lo (15 mg/kg/d YD, 10 weeks), YD-hi (30 mg/kg/d YD, 10 weeks), positive drug (TAK-875), and healthy control groups. The rats underwent an oral glucose tolerance test (OGTT), glucose-stimulated insulin secretion (GSIS) test, and serum lipid measurements. High-fat and high-glucose-injured RIN-m5f cells were treated with YD (30 or 150 mg/mL) for 48 h. GPR40 and IP3R-1 expression levels were determined by immunofluorescence, qRT-PCR, and western blot.Results: Compared with the model group, the OGTT area under the curve (AUC) in the YD-hi group was decreased by 26.7%, the insulin release test (IRT) AUC in the YD-hi group was increased by 45.9%, and the GSIS AUC was increased by 33.9% (p &lt; 0.05). Compared with the model cells, the insulin secretion after glucose stimulation in the YD-hi group was increased by 24.5%, similar to the TAK-875 group (23.1%) (p &gt; 0.05). GPR40 and IP3R-1 mRNA in the model cells were decreased by 49.5% and 51.2% compared with the control cells (p &lt; 0.05). In the YD-hi group, GPR40 and IP3R-1 mRNA levels were increased by 58.1% and 39.3% (p &lt; 0.05), similar to the TAK-875 group. The changes in protein expression were similar to mRNA.Conclusion: YD promotes insulin secretion from pancreatic islet β-cell in T2DM rats by regulating the GPR40-IP3R-1 pathway, thereby reducing blood glucose.
Differing hypertrophy patterns from open and closed kinetic chain training affect quadriceps femoris center of mass and moment of inertia
Authors: Earp Jacob E. , Angelino Domenic , Hatfield Disa L. , Colantuono Vincent , Jackson Euan R. , Morgan Kristin D. , Adami Alessandra , Melanson Kathleen J. , Blazevich Anthony J. 
Published: March 2023

Purpose: To determine whether kinetic chain pattern during knee extensor strength training influences quadriceps femoris center of mass and moment of inertia about the hip in a predictable manner as such changes can affect running economy.Methods: Twelve participants completed 8 weeks of both unilateral open (OKC) and closed (CKC) kinetic chain resistance training on opposing legs. Changes in quadriceps femoris muscle volume (VOLQF), center of mass location (CoMQF), and moment of inertia (IQF) about the hip were determined from magnetic resonance images scans. Regional hemodynamics of the vastus lateralis taken at 30% and 70% of muscle length during OKC and CKC bouts early in the training program were measured using near-infrared spectroscopy (NIRS) and used post hoc to predict changes in CoMQF.Results: While increases in VOLQF were similar between OKC (Δ79.5 ± 87.9 cm3) and CKC (Δ60.2 ± 110.5 cm3, p = 0.29), the patterns of hypertrophy differed; a distal shift in CoMQF (Δ2.4 ± 0.4 cm, p &lt; 0.001) and increase in IQF (Δ0.017 ± 0.014 kg m2, p &lt; 0.001) occurred in OKC but not in CKC (CoMQF: Δ-2.2 ± 2.0 cm, IQF: Δ-0.022 ± 0.020 kg m2, p &gt; 0.05). Regional hemodynamics assessed by NIRS during a single training session displayed similar exercise and regional differences and predicted 39.6% of observed changes in CoMQF.Conclusions: Exercise selection influences muscle shape sufficiently to affect CoMQF and IQF, and these changes may be predicted in part from NIRS measurements during a single workout. Given IQF is inversely related to running economy and since CKC exercise provides a more proximal pattern of hypertrophy than OKC, it may be more preferential for running. The results from the present study also highlight the potential of NIRS as a tool for predicting patterns of hypertrophy between different exercises and exercise conditions.