bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of the Ketogenic Diet for Mitochondrial Disease With Epilepsy: A Prospective, Open-labeled, Controlled Study
Authors: Huang Lijuan , Li Hua , Zhong Jianmin , Yang Liming , Chen Guohong , Wang Dong , Zheng Guo , Han Hong , Han Xiong , Long Yiqin , Wang Xu , Liang Jianmin , Yu Mei , Shen Xiaoyun , Fan Mengke , Fang Fang , Liao Jianxiang , Sun Dan 
Published: August 2022

BackgroundThe ketogenic diet (KD) is increasingly used to treat drug-resistant epilepsy because of its favorable effect on seizure reduction. Patients with mitochondrial diseases tend to experience seizures. Therefore, this study aimed to test the efficacy of the KD on participants with mitochondrial diseases in a controlled trial.MethodsParticipants from fourteen clinical centers who were diagnosed with mitochondrial disease were semi-randomized to either the intervention (KD) or control group. The KD group followed a 3-month KD intervention, while the control group received a 1-month normal diet initially and then a 3-month KD intervention. The primary outcome measure was seizure reduction. Biomarker changes, cognitive impairments, and side effects were also recorded, if available.ResultA total of 33 participants were assigned to the KD (n = 22) and control groups (n = 11). In the KD group, 31.8% (7/22) of participants achieved ≥50% seizure reduction after 1 month of diet intervention, which increased to 40.9% (9/22) at 3 months. In the control group, only 18.2% (2/11) of the participants had ≥50% seizure reduction during the normal diet period. After the control group was transferred to the KD, 63.6% (7/11) of participants had &gt;50% seizure reduction, and this rate increased to 72.7% (8/11) at 3 months. The KD also showed high efficacy in participants with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) or pathogenic variants in mitochondrial DNA (mtDNA) (90% and 93.3% response rates, respectively). The most frequent side effects reported at the 3-month review were vomiting, cold, hyperlipidemia, and bloating.ConclusionThe KD is a safe and effective therapy for seizure control in mitochondrial diseases, especially MELAS and pathogenic variants of mtDNA. KD intervention can be considered in the management of these patients.
Age-, sex-, and maturity-associated variation in the phase angle after adjusting for size in adolescents
Authors: de Moraes Anderson M. , Quinaud Ricardo T. , Ferreira Giovana O. C. , Lima Ahlan B. , Carvalho Humberto M. , Guerra-Júnior Gil 
Published: August 2022

BackgroundApplied research using the phase angle (PhA) in children and adolescents has increased notably. Using multilevel modeling in a fully Bayesian framework, we examined the relationships between PhA, age, sex, biological maturity status, and body size in 10–16-year-old adolescents.MethodsThe sample comprised 519 adolescents (women, n = 241; men, n = 278) from Campinas, São Paulo, Brazil. Biological maturity status was assessed with self-examination of pubertal development for sexual maturity and maturity offset protocol to estimate age at peak height velocity (PHV) for somatic maturity status. Stature and body mass were measured by anthropometry. Phase angle was calculated based on raw resistance and reactance values (50 kHz frequency) obtained by bioelectrical impedance with the foot-to-hand technology.ResultsThe multilevel regression analysis revealed that boys had significantly higher values of phase angle than girls, adjusting for age group and sexual maturity status. Overall, older and more mature adolescents had higher values of phase angle. When considering aligning variation in the phase angle by distance to estimated PHV (maturity offset), there was a higher association between the phase angle and time before and after predicted age at PHV for boys (r = 0.31, 90% CI: 0.23 to 0.39) than girls (r = 0.2, 90% CI: 0.11 to 0.28). When including body mass in the multilevel models, corresponding changes in the overall body mass mediate most of the influence of the maturity status and age group on the phase angle.ConclusionThe present study demonstrated that the variability in phase angle is related to inter-individual variation in sex, age, and maturity status, as well as differences in body size. Research with adolescents considering phase angle should use multilevel modeling with standardized parameters as default to adjust for the concurrent influence of sex, age, maturity status, and body size.
Circulating choline pathway nutrients and risk of moyamoya disease
Authors: Ge Peicong , Zhao Yaobo , Zhai Yuanren , Zhang Qian , Ye Xun , Wang Jia , Wang Rong , Zhang Yan , Zhang Dong , Zhao Jizong 
Published: August 2022

BackgroundCirculating choline pathway nutrients play a critical role in first stroke and recurrent stroke. However, there is limited information available on the effects of choline pathway nutrients on the risk of moyamoya disease (MMD) and its subtypes. We investigated the association between circulating choline and betaine and the incident risk of MMD and its subtypes.MethodsThe case-control study enrolled 385 patients with MMD [i.e., 110 transient ischemic attack (TIA)-type MMD, 157 infarction-type MMD, and 118 hemorrhagic-type MMD] and 89 matched healthy controls.ResultsSerum choline and betaine were inversely related to the risk of MMD and its subtypes. The risk of MMD was decreased with each increment in choline level [per 1 μmol increase: odds ratio (OR), 0.756; 95% CI, 0.678–0.843] and betaine level (per 1 μmol increase: OR, 0.952; 95% CI, 0.932–0.972), respectively. When choline and betaine were assessed as quartiles, compared with the lowest quartile of serum choline and betaine levels, those in the highest quartile had a significantly decreased risk of MMD (choline, Q4 vs. Q1: OR, 0.023; 95% CI, 0.005–0.118; betaine, Q4 vs. Q1: OR, 0.058; 95% CI, 0.018–0.184).ConclusionsSerum choline and betaine were associated with the decreased risk of MMD and its subtypes.
Cyclic adenosine monophosphate/phosphodiesterase 4 pathway associated with immune infiltration and PD-L1 expression in lung adenocarcinoma cells
Authors: Tong Ling , Shan Minjie , Zou Wen , Liu XianLing , Felsher Dean W. , Wang Jingjing 
Published: August 2022

BackgroundThe cyclic adenosine monophosphate/phosphodiesterase 4 (cAMP/PDE4) pathway is involved in inflammation and immune regulation; however, the effect of cAMP/PDE4 on immune infiltration and immune evasion in lung adenocarcinoma (LUAD) remains unclear.MethodsCBioPortal, which is the The Cancer Genome Atlas (TCGA) online database, and the Kaplan Meier plotter were used to analyze the association between genes and the prognosis of TCGA-LUAD. Tumor Immune Estimation Resource (TIMER) was used to analyze the association between gene expression and immune infiltration. The Genecards database was used to identify the transcription factors of related genes. The lung adenocarcinoma cell line H1299 and A549 were treated with cAMP pathway drugs. Flow cytometry and qRT-PCR were used to detect the PD-L1 protein and gene expression, respectively. A one-way analysis of variance with Tukey’s post-hoc test or a Student’s t-test were used.ResultsIt was found that PDE4B and CREB1, which are downstream genes of the cAMP/PDE4 axis, were differentially expressed in LUAD and adjacent tissues and are correlated with the prognosis and immune infiltration of LUAD. In the CBioPortal database, cAMP pathway genes are closely related to programmed cell death-ligand 1 (PD-L1) expression in TCGA-LUAD. The protein-protein interaction revealed that there was a direct interaction between CREB1/CREBBP, which are the downstream molecules of the cAMP/PDE4 axis, and MYC; additionally, MYC was predicted to bind to the PD-L1 transcription site and regulate PD-L1 expression. CREB1 was also predicted to transcriptionally bind to both MYC and PD-L1. These results predicted the interaction network of cAMP/PDE4/CREB1/CREBP/MYC/PD-L1, and the core factor may be related to MYC. In the cell experiment, forskolin (an adenylate cyclase activator) and zardaverine (a PDE4 inhibitor) enhance the cAMP pathway and decrease PD-L1 expression, while SQ2253 (an adenylate cyclase inhibitor) inhibits the cAMP pathway and increases PD-L1 expression of the LUAD cell lines H1299 and A549, and MYC regulation by these drugs was positively correlated with PD-L1 regulation, which verified the regulation of the cAMP/PDE4 pathway on MYC and PD-L1.ConclusionsThis study showed that the cAMP/PDE4 pathway may play an important role in PD-L1 regulation and immune infiltration in LUAD.
Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11
Authors: Gao Huijie , He Zhaobin , Gao Chao , Liu Naiqing , Zhang Zhaoyang , Niu Weibo , Niu Jun , Peng Cheng 
Published: August 2022

ObjectiveCholangiocarcinoma (CHOL) is a deadly cancer worldwide with limited available therapies. The aim of this study was to investigate key exosomal miRNAs and their functions in CHOL development.MethodsSerum exosomes were isolated from patients with CHOL and healthy controls, followed by miRNA sequencing for identifying differentially expressed miRNAs (DEMs) and their functions. Then, the expression of key DEMs was experimentally validated in exosomes from clinical CHOL patients and CHOL cells. The effects of overexpression of key DEMs on CHOL cell migration and proliferation were investigated. A key exosomal DEM miR-3124-5p was identified. The effects of overexpression or knockdown of exosomal miR-3124-5p on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were investigated. Moreover, the function of exosomal miR-3124-5p on tumor growth in vivo was explored.ResultsA total of 632 exosomal DEMs were identified between CHOL and control samples. Target genes of DEMs were significantly enriched in pathways, such as the p53 signaling pathway. miR-3124-5p was upregulated in serum exosomes from CHOL patients and exosomes from CHOL cells, and overexpression of miR-3124-5p promoted RBE cell migration and viability. Moreover, overexpression of exosomal miR-3124-5p promoted the proliferation, migration, and angiogenesis of HUVECs, while knockdown of miR-3124-5p had the opposite effect. miR-3124-5p could target growth differentiation factor 11 (GDF11) and downregulate GDF11 expression. Furthermore, exosomal miR-3124-5p promoted tumor growth in vivo.ConclusionsOur findings revealed that exosome-encapsulated miR-3124-5p promoted the malignant progression of CHOL by targeting GDF11. Exosomal miR-3124-5p and GDF11 could be promising biomarkers or therapeutic targets for CHOL.
Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
Authors: Sun Guangyu , Ma Shenfei , Zheng Zhiwen , Wang Xiaohua , Chen Shuaiqi , Chang Taihao , Liang Zhengxin , Jiang Yuchen , Xu Shengxian , Liu Ranlu 
Published: August 2022

BackgroundProstate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransferase for m5c RNA modification, the role of the NSUN members (NSUN1-7) in prostate cancer is unclear.MethodsWe obtained sequencing data of genes and related clinical data of prostate cancer from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database and analyzed the correlation between NSUN members’ expression and prognosis. we found that NSUN2 was closely implicated in the prognosis of prostate cancer, then verified the expression of NSUN2 in clinical samples, and obtained the correlation between NSUN2 and immune cell infiltration through CIBERSORT algorithm and ESTIMATE method. The relationship between NSUN2 copy number variation and immune cell infiltration was further analyzed in the TIMER database and identified signaling pathways associated with NSUN2 expression by GO, KEGG, and GSEA analysis. Finally, we verified the expression of NSUN2 in prostate cancer cell lines and confirmed the role of NSUN2 on the biological behavior of prostate cancer cells by proliferation and migration-related assays.ResultsNOP2 and NSUN2 were upregulated in prostate tumor tissues. NSUN2 expression is closely associated with tumor prognosis. NSUN2 high expression implies poor clinical features, and the NSUN family is significantly associated with tumor stromal score and immune score. Besides, NSUN2 is associated with a variety of immune infiltrating cells (B cells memory, T cells CD4 memory resting, T cells CD4 memory activated, NK cells resting, and so on). High NSUN2 expression lowers the sensitivity of many chemotherapy drugs, such as docetaxel, doxorubicin, fluorouracil, cisplatin, and etoposide. In prostate cancer, the most common type of mutation in NSUN2 is amplification, and NSUN2 copy number variation is closely associated with NSUN2 expression and immune cell infiltration. GSEA analysis showed that the related genes were mainly enriched in ubiquitin-mediated protein hydrolysis, cell cycle, RNA degradation, endometrial cancer, prostate cancer, p53 signaling pathway, and NSUN2 potentiated the proliferation and migration of prostate cancer cells.ConclusionsNSUN2 is highly expressed in prostate cancer, which contributes to the progression of prostate cancer, and is closely implicated in immune cell infiltration and chemotherapy drugs. NSUN2 is expected to be a prospective marker and a new treatment target for prostate cancer.
Adolescent social emotional skills, resilience and behavioral problems during the COVID-19 pandemic: A longitudinal study in three European countries
Authors: Martinsone Baiba , Stokenberga Ieva , Damberga Ilze , Supe Inga , Simões Celeste , Lebre Paula , Canha Lúcia , Santos Margarida , Santos Anabela Caetano , Fonseca Ana Marta , Santos Dória , Gaspar de Matos Margarida , Conte Elisabetta , Agliati Alessia , Cavioni Valeria , Gandellini Sabina , Grazzani Ilaria , Ornaghi Veronica , Camilleri Liberato 
Published: August 2022

ObjectivesThe consequences of long-lasting restrictions related to the COVID-19 pandemic have become a topical question in the latest research. The present study aims to analyze longitudinal changes in adolescents’ social emotional skills, resilience, and behavioral problems. Moreover, the study addresses the impact of adolescents’ social emotional learning on changes in their resilience and behavioral problems over the course of seven months of the pandemic.MethodsThe Time 1 (T1) and Time 2 (T2) measuring points were in October 2020 and May 2021, characterized by high mortality rates and strict restrictions in Europe. For all three countries combined, 512 questionnaires were answered by both adolescents (aged 11-13 and 14-16 years) and their parents. The SSIS-SEL and SDQ student self-report and parent forms were used to evaluate adolescents’ social emotional skills and behavioral problems. The CD-RISC-10 scale was administered to adolescents to measure their self-reported resilience. Several multilevel models were fitted to investigate the changes in adolescents’ social emotional skills, resilience, and behavioral problems, controlling for age and gender. Correlation analysis was carried out to investigate how changes in the adolescents’ social emotional skills were associated with changes in their resilience and mental health adjustment.ResultsComparing T1 and T2 evaluations, adolescents claim they have more behavioral problems, have less social emotional skills, and are less prosocial than perceived by their parents, and this result applies across all countries and age groups. Both informants agree that COVID-19 had a negative impact, reporting an increment in the mean internalizing and externalizing difficulties scores and reductions in social emotional skills, prosocial behavior, and resilience scores. However, these changes are not very conspicuous, and most of them are not significant. Correlation analysis shows that changes in adolescents’ social emotional skills are negatively and significantly related to changes in internalized and externalized problems and positively and significantly related to changes in prosocial behavior and resilience. This implies that adolescents who experienced larger development in social emotional learning also experienced more increase in resilience and prosocial behavior and a decrease in difficulties.ConclusionDue to its longitudinal design, sample size, and multi-informant approach, this study adds to a deeper understanding of the pandemic’s consequences on adolescents’ mental health.
Actively incorporating lifestyle modifications into daily life: The key to adherence in a lifestyle intervention programme for metabolic syndrome
Authors: Wang Qun , Chair Sek Ying , Wong Eliza Mi Ling , Qiu Xichenhui 
Published: August 2022

IntroductionLifestyle modifications are the first-line interventions for metabolic syndrome (MetS) management. The effectiveness of lifestyle interventions depends mostly on participants' adherence to the interventions. The current study was to explore the experiences of MetS patients in attending lifestyle intervention program (LIP) and the factors that influenced their adherence to the interventions.MethodsA descriptive qualitative study was designed following the COREQ guideline. Face-to-face semi-structured individual interviews were conducted with a purposive sample from the participants who attended the LIP using the data saturation principle. Content analysis of transcripts was conducted following the methods proposed by Graneheim and Lundman.ResultsThe study recruited 27 participants, including 13 males and 14 females. Four themes were identified: (i) the positive and beneficial experiences of attending the LIP, including incorporating lifestyle modifications into daily life, improved physical and psychological health, and empowerment; (ii) facilitators of adherence, including individualized lifestyle education, regular follow-ups, and adequate interpersonal support; (iii) barriers to adherence, including personal resistance, competing demands, and contextual factors; (iv) suggestions for future interventions: with multidisciplinary team, longer term intervention, and more efficient approaches. The findings also indicated that young-to-middle aged patients faced more conflicts with role-related commitments, and were open for e-approaches in lifestyle interventions.ConclusionThe LIP provided positive and beneficial experiences for the participants. Actively incorporating lifestyle modifications into daily life is the key to maintain participants' adherence to the LIP. Culturally appropriate and psycho-behavioral strategies should be adopted to overcome personal and contextual barriers. Special attentions should be paid for the young-to-middle aged population in MetS management.
Understanding exercise addiction, psychiatric characteristics and use of anabolic androgenic steroids among recreational athletes – An online survey study
Authors: Gunnarsson Björn , Entezarjou Artin , Fernández-Aranda Fernando , Jiménez-Murcia Susana , Kenttä Göran , Håkansson Anders 
Published: August 2022

BackgroundThe purpose of this paper was to explore maladaptive behaviors among physically active individuals, including exercise dependence and use of anabolic steroids. Both exercise addiction (EA) and use of anabolic androgenic steroids (AAS) correlate to high amounts of exercise and EA have been linked to eating disorders and other mental health problems.MethodsAn internet survey was spread through fitness-related social media. Inclusion criteria were age ≥ 15 years and exercise frequency ≥ thrice weekly. Exercise addiction inventory identified those at-risk of EA (rEA). Characteristics of rEA were compared to those not at risk. In a separate analysis, AAS users were compared to AAS-naïve individuals.ResultsIn total, 3,029 participants completed the questionnaire. Of these, 11% screened positive for being rEA, and 23% for ED. Factors associated with EA included daily exercise, social phobia, eating disorders and OCD. Risk consumption of alcohol was a negative predictor. Thirty seven participants had taken AAS the last year. These were mainly men, bodybuilders/powerlifters and more often used amphetamines and opioids.DiscussionThis exploratory study supports EA being strongly associated with eating disorders. Identified associations between EA and compulsive or anxiety disorders warrant further research to clarify if these associations arise prior to, together with, or secondary to EA.
Direct and Rapid Identification of Vibrio Cholerae Serogroup and Toxigenicity by a Novel Multiplex Real-Time Assay
Authors: Yan Yong , Zhan Li , Zhu Guoying , Zhang Junyan , Li Ping , Chen Lixia , He Peiyan , Luo Jianyong , Chen Zhongwen 
Published: August 2022

Molecular diagnostic assays for cholera detection have superior sensitivity to conventional assays and are now being accepted as the new standard method, especially the real-time PCR/RT-PCR. However, limited throughput capacity and long detection duration prevent them from detecting more specimens and more targets in one turnaround time simultaneously. In this study, we utilized nucleic acid extraction-free, direct RT-PCR and high-speed amplification to develop a novel multiplex assay, a quadplex direct one-tube real-time RT-PCR assay, for rapid detection of the serogroup and cholera toxin toxigenicity of Vibrio cholerae targeting the epsM, ctxA, rfb-O1, and rfb-O139 genes. Performance of the multiplex assay was evaluated by comparison with the monoplex real-time PCR assay according to the China Cholera Prevention Manual. Detection data from clinical specimens showed that the new assay had good diagnostic sensitivities for epsM (100%, n = 301), ctxA (100%, n = 125), rfb-O1 (100%, n = 85), and rfb-O139 (97.87%, n = 49). Analysis of the analytical sensitivities with serial dilutions of positive standards showed that the detection limits of the new assay for Vibrio cholerae epsM,ctxA,rfb-O1, and rfb-O139 were up to 200, 590, 115, and 1052 copies per mL lower than the monoplex real-time PCR (910, 345, and 1616 copies/mL respectively, for ctxA,rfb-O1, and rfb-O139). The results indicate that the multiplex assay is a rapid, sensitive, specific, and easy-to-use detection tool for Vibrio cholerae, especially suitable for rapid identification and screening detection of mass specimens.
Rancang Bangun Oksimeter Pulsa yang Diintegrasikan dengan EKG sebagai Alat Ukur Multimodal untuk Analisis HRV
Authors: Pang David , Kolibu Hesky Stevy 
Published: August 2022

Analisis variabilitas denyut jantung (HRV) berdurasi panjang berguna sebagai teknik noninvasif untuk asesmen terhadap aktivitas sistem saraf otonom. Analisis Ini menginformasikan banyak faktor fisiologis dan patologis yang memodulasi detak jantung normal. Namun performa sistem analisis HRV sangat bergantung pada keakurasian pendeteksian R-peak dari QRS complex. Detak yang disebabkan oleh kesalahan deteksi dapat menggangu hasil HRV, yang mengakibatkan masalah signifikan dalam interpretasinya. Terutama sifatnya yang berdurasi panjang, maka diperlukan sistem deteksi R-peak yang andal. Penelitian ini bertujuan membangun sistem akuisisi data multimodal dari data EKG dan data pulsa SPO2 untuk mendapatkan hasil deteksi R-peak yang lebih reliabel dibanding dengan hanya menggunakan data EKG saja. Namun demikian, hasil akhir sistem keseluruhan ditentukan oleh metode pendeteksian yang nantinya digunakan .