bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-alcoholic Fatty Liver Disease and the Risk of Incident Atrial Fibrillation in Young Adults: A Nationwide Population-Based Cohort Study
Authors: Choi JungMin , Lee So-Ryoung , Choi Eue-Keun , Ahn Hyo-Jeong , Kwon Soonil , Park Sang-Hyeon , Lee HuiJin , Chung Jaewook , Han MinJu , Lee Seung-Woo , Han Kyung-Do , Oh Seil , Lip Gregory Y. H. 
Published: March 2022

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a multisystem disease including cardiovascular. However, the association between NAFLD and the risk of incident atrial fibrillation (AF), especially in young adults, remains unclear. We aimed to evaluate the association between NAFLD as assessed by the fatty liver index (FLI) and the risk of AF in young adults.MethodsWe identified individuals aged 20–39 years who underwent health examinations conducted by the Korean National Health Insurance Corporation between January 2009 and December 2012. Individuals with significant liver disease, heavy alcohol consumption, or prevalent AF were excluded. We categorized based on FLI: &lt;30, 30 to &lt;60, and ≥60. Incident AF was evaluated as the primary outcome.ResultsWe included 5,333,907 subjects (mean age, 31 ± 5 years; men, 57%). During a mean follow-up of 7.4 ± 1.1 years, 12,096 patients had newly diagnosed AF (incidence rate 0.31 per 1,000 person-years). After adjustment, subjects with FLI 30 to &lt;60 and FLI ≥60 showed a higher risk of AF compared to those with FLI &lt;30 (hazard ratio [HR] 1.21, 95% confidence interval [CI, 1.15–1.27] and HR 1.47, 95% CI [1.39–1.55], p &lt; 0.001, respectively). In women, the increased AF risk was accentuated in the higher FLI group than in the individuals with FLI &lt;30, compared with men (p-for-interaction = 0.023). A higher incident AF risk in the higher FLI groups was consistently observed in various subgroups.ConclusionAmong young adults, NAFLD assessed using FLI was positively correlated with the AF risk. These findings support the evidence of AF screening in young adults with high FLI scores.
Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Zheng Yong-Tian , Xiao Tian-Mei , Wu Chan-Xian , Cheng Jin-Yan , Li Le-Yu 
Published: March 2022

BackgroundIncreasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two.MethodsThe PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P &lt; 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P &lt; 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P &lt; 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P &lt; 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P &lt; 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01).ConclusionPolymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.
Plasma Circulating Vitamin C Levels and Risk of Endometrial Cancer: A Bi-Directional Mendelian Randomization Analysis
Authors: Peng Haoxin , Wu Xiangrong , Wen Yaokai 
Published: March 2022

BackgroundObservational studies indicated that circulating vitamin C (VitC) levels may be correlated with the risk of endometrial cancer (EC). However, the causal effects and direction between them were still unclear.MethodsIn this study, 11 single nucleotide polymorphisms (SNPs) robustly correlated with plasma VitC levels were extracted from the latest genome-wide association study (GWAS), containing 52,018 individuals. Genetic data of EC were obtained from the Endometrial Cancer Association Consortium (ECAC) (12,906 cases and 108,979 controls). An inverse-variance weighted method was utilized as the primary analysis of Mendelian randomization (MR), supplemented by the weighted median, MR Pleiotropy Residual Sum and Outlier test (MR-PRESSO), and MR-Egger methods. Additional sensitivity analyses excluding 3 SNPs with secondary phenotypes were conducted to rule out the possible pleiotropic effects. Potential impacts of several risk factors of EC, such as obesity, body mass index (BMI), hypertension, and diabetes on VitC levels, were assessed. We additionally evaluated the effects of VitC on LDL cholesterol levels, HDL cholesterol levels, and triglycerides levels to probe into the possible mediators in the VitC-EC pathway.ResultsGenetically predicted higher plasma VitC levels (per 1 SD increase, approximately 20 μmol/L) were causally associated with an increased risk of EC overall [odds ratio (OR) 1.374, 95%CI1.128–1.674,p= 0.0016], supported by complementary sensitivity analyses. In the subgroup analyses, genetically predicted higher levels of VitC were associated with a tendency of increased risks of both endometrioid (ORSD1.324, 95%CI0.959–1.829,p= 0.0881) and non-endometrioid histology (ORSD1.392, 95%CI0.873–2.220,p= 0.1647) while without statistical significance. The association remained significant after the exclusion of the three pleiotropic SNPs (ORSD1.394, 95%CI1.090–1.784,p= 0.0082). The confounders and mediators were unlikely to affect the VitC-EC relationship. The causal effect of EC on VitC levels was not supported (OR1.001, 95%CI0.998–1.004,p= 0.4468).ConclusionsThis bi-directional MR study demonstrated a causal risk role of higher circulating VitC at physiological levels on an increased risk of EC, which was independent of confounders and mediators. Further studies are warranted to elucidate the possible mechanisms.
β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain
Authors: Ropero Paloma , González Fernández Fernando Ataúlfo , Nieto Jorge M. , Torres-Jiménez Williana Melissa , Benavente Celina 
Published: March 2022

ObjectivesTo verify with hematimetric data that the diagnosis and clinical grade of β-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous β-thalassemia coexist.Materials and MethodsRetrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and β-thalassemia.Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of β-thalassemia was carried out by automatic sequencing according to the Sanger method.ResultsThe genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the β globin gene. All had a mutation in the HBB gene (β0-thalassemia, β+-thalassemia severe, and β+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the β and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F.ConclusionsIn group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous β-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes.
Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Papillary Renal Cell Carcinoma
Authors: Zhang Chiyu , Huang Ruizhen , Xi Xiaoqing 
Published: March 2022

Background: Immunotherapy has emerged as an important technique for treating a variety of cancers. The dynamic interplay between tumor cells and invading lymphocytes in the tumor microenvironment is responsible for the good response to immunotherapy (TME). Pyroptosis, or inflammation-induced cell death, is closely linked to a number of cancers. However, in papillary renal cell carcinoma (KIRP), the association between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy impact remains unknown.Methods: We carefully investigated the link between pyroptosis and tumor growth, prognosis, and immune cell infiltration by evaluating 52 pyroptosis-related genes. The PRG score was utilized to measure a single tumor patient’s pyroptosis pattern. After that, we looked at how well these values predicted prognoses and therapy responses in KIRP.Results: We discovered that PRG differences between subgroups were linked to clinical and pathological aspects, prognosis, and TME in two separate genetic subtypes. After that, a PRG score for estimating overall survival (OS) was developed, and its predictive potential in KIRP patients was confirmed. As a result, we developed a very precise nomogram to improve the PRG score’s clinical usefulness. A low PRG score, which is determined by mutation load and immune activation, suggests a good chance of survival. Furthermore, the PRG score was linked to chemotherapeutic drug sensitivity in a substantial way.Conclusions: The possible functions of PRGs in the TME, clinical and pathological characteristics, and prognosis were established in our thorough investigation of PRGs in KIRP. These results might help us better understand PRGs in KIRP and offer a new avenue for prognostic evaluation and the development of more effective immunotherapy treatments.
Altered Brain Activity in Depression of Parkinson’s Disease: A Meta-Analysis and Validation Study
Authors: Su Dongning , Cui Yusha , Liu Zhu , Chen Huimin , Fang Jinping , Ma Huizi , Zhou Junhong , Feng Tao 
Published: March 2022

BackgroundThe pathophysiology of depression in Parkinson’s disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis.MethodsWe searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis.ResultsA total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043).ConclusionOur study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD.
The Impact of Exercise and Virtual Reality Executive Function Training on Cognition Among Heavy Drinking Veterans With Traumatic Brain Injury: A Pilot Feasibility Study
Authors: Pennington David L. , Reavis Jill V. , Cano Monique T. , Walker Erica , Batki Steven L. 
Published: March 2022

Executive function (EF) underlies self-control deficits in alcohol use disorder (AUD) and traumatic brain injury (TBI). Cognitive training is a promising adjunctive treatment targeting TBI- and AUD- related cognitive dysfunction. However, major limitations related to compliance and generalizability in the field of cognitive training exist. Physical activity is associated with enhanced cognitive performance across several executive functions and may enhance the benefits of cognitive training. Virtual reality provides multisensory embodied experiences which are likely to engage brain networks more efficiently than standard cognitive training systems, ultimately resulting in greater near- and far-transfer effects. This pilot study aimed to obtain feasibility data and a preliminary assessment of an enriched virtual reality (VR) EF training (EFT) intervention combined with exercise (NCT03786276). Using an 8-week randomized adaptive design study, 30 AUD treatment seeking U.S. Veterans completed nine sessions of exercise-only (n = 15) or gameplay control (n = 15) over 3 weeks, followed by a week-4 repeat assessment in Phase 1. Twenty-three participants completed and moved onto Phase II, where they completed up to nine sessions of VR-EFT plus exercise and completed a week-8 end-of-study assessment. Primary outcomes included feasibility to retain participants, usability, and satisfaction of using VR-EFT. Secondary and exploratory outcomes included within group assessment of change in cognitive function, alcohol use, alcohol craving, and post-concussive symptoms among the three treatment conditions.VR-EFT was feasible with moderate usability and high acceptability ratings.The most common VR-related adverse effect was motion sickness (n = 2/16, 12.5%). The VR-EFT condition was associated with significant improvement in inhibition-switching and visual scanning (both p &lt; 0.05) during Phase II. Exercise-only was associated with significant improvements in cognitive inhibition, cognitive flexibility, reductions in alcohol craving, and number of standard alcohol drinks per week (all p ≤ 0.05). The gaming-control condition was associated with improvement in cognitive flexibility and visuospatial immediate recall (both p &lt; 0.05) during Phase 1. Recruitment and retention of U.S. veterans with AUD and TBI into an exercise plus VR-EFT intervention is feasible, but technological barriers may impact usability. VR-EFT was associated with improvement in executive function domains that were targeted in as little as 3-week and nine sessions of VR-EFT exposure. Results are promising and indicate the need for a larger controlled investigation to assess the efficacy of VR-EFT to enhance treatment outcomes among AUD treatment-seeking U.S. veterans with co-occurring AUD and TBI.Clinical Trial Registrationwww.ClinicalTrials.gov, Identifier: NCT03786276.
Are Smartwatches a Suitable Tool to Monitor Noise Exposure for Public Health Awareness and Otoprotection?
Authors: Fischer Tim , Schraivogel Stephan , Caversaccio Marco , Wimmer Wilhelm 
Published: March 2022

Introduction and ObjectivesNoise-induced hearing loss (NIHL) and tinnitus are common problems that can be prevented with hearing protection measures. Sound level meters and noise dosimeters enable to monitor and identify health-threatening occupational or recreational noise, but are limited in their daily application because they are usually difficult to operate, bulky, and expensive. Smartwatches, which are becoming increasingly available and popular, could be a valuable alternative to professional systems. Therefore, the aim of this study was to evaluate the applicability of smartwatches for accurate environmental noise monitoring.MethodsThe A-weighted equivalent continuous sound pressure level (LAeq) was recorded and compared between a professional sound level meter and a popular smartwatch. Noise exposure was assessed in 13 occupational and recreational settings, covering a large range of sound pressure levels between 35 and 110 dBA. To assess measurement agreement, a Bland-Altman plot, linear regression, the intra-class correlation coefficient, and descriptive statistics were used.ResultsOverall, the smartwatch underestimated the sound level meter measurements by 0.5 dBA (95% confidence interval [0.2, 0.8]). The intra-class correlation coefficient showed excellent agreement between the two devices (ICC = 0.99), ranging from 0.65 (music club) to 0.99 (concert) across settings. The smartwatch's sampling rate decreased significantly with lower sound pressure levels, which could have introduced measurement inaccuracies in dynamic acoustic environments.ConclusionsThe assessment of ambient noise with the tested smartwatch is sufficiently accurate and reliable to improve awareness of hazardous noise levels in the personal environment and to conduct exploratory clinical research. For professional and legally binding measurements, we recommend specialized sound level meters or noise dosimeters. In the future, smartwatches will play an important role in monitoring personal noise exposure and will provide a widely available and cost-effective measure for otoprotection.
Human Galectin-7 Gene LGALS7 Promoter Sequence Polymorphisms and Risk of Spontaneous Intracerebral Hemorrhage: A Prospective Study
Authors: Wang Ming-Dong , Tian Jing , Zhang John H. , Zhao Shun-Ying , Song Ming-Jing , Wang Zhan-Xiang 
Published: March 2022

Background and purposeDespite evidence for the role of genetic factors in stroke, only a small proportion of strokes have been clearly attributed to monogenic factors, due to phenotypic heterogeneity. The goal of this study was to determine whether a significant relationship exists between human galectin-7 gene LGALS7 promoter region polymorphisms and the risk of stroke due to non-traumatic intracerebral hemorrhage (ICH).MethodsThis two-stage genetic association study included an initial exploratory stage followed by a discovery stage. During the exploratory stage, transgenic galectin-7 mice or transgenic mice with the scrambled sequence of the hairpin structure –silenced down gene LGALS7—were generated and then expressed differentially expressed proteins and galectin-7-interacting proteins were identified through proteomic analysis. During the discovery stage, a single-nucleotide polymorphism (SNP) genotyping approach was used to determine associations between 2 LGALS7 SNPs and ICH stroke risk for a cohort of 24 patients with stroke of the Chinese Han population and 70 controls.ResultsDuring the exploratory phase, LGALS7 expression was found to be decreased in TGLGALS–DOWN mice as compared to its expression in TGLGALS mice. During the discovery phase, analysis of LGALS7 sequences of 24 non-traumatic ICH cases and 70 controls led to the identification of 2 ICH susceptibility loci: a genomic region on 19q13.2 containing two LGALS7 SNPs, rs567785577 and rs138945880, whereby the A allele of rs567785577 and the T allele of rs138945880 were associated with greater risk of contracting ICH [for T and A vs. C and G, unadjusted odds ratio (OR) = 13.5; 95% CI = 2.249–146.5; p = 0.002]. This is the first study to genotype the galectin-7 promoter in patients with hemorrhagic stroke. Genotype and allele association tests and preliminary analysis of patients with stroke revealed that a single locus may be a genetic risk factor for hemorrhagic stroke.ConclusionA and T alleles of two novel SNP loci of 19q13.2, rs567785577 and rs138945880, respectively, were evaluated for associations with susceptibility to ICH. Further studies with expanded case numbers that include subjects of other ethnic populations are needed to elucidate mechanisms underlying associations between these SNPs and ICH risk.
The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea
Authors: Edvardsson Rasmussen Jesper , Lundström Patrik , Eriksson Per Olof , Rask-Andersen Helge , Liu Wei , Laurell Göran 
Published: March 2022

BackgroundFurosemide is a loop diuretic used to treat edema; however, it also targets the Na-K-Cl cotransporter-1 (NKCC1) in the inner ear. In very high doses, furosemide abolishes the endocochlear potential (EP). The aim of the study was to gain a deeper understanding of the temporal course of the acute effects of furosemide in the inner ear, including the protein localization of Fetuin-A and PEDF in guinea pig cochleae.Material and MethodAdult guinea pigs were given an intravenous injection of furosemide in a dose of 100 mg per kg of body weight. The cochleae were studied using immunohistochemistry in controls and at four intervals: 3 min, 30 min, 60 min and 120 min. Also, cochleae of untreated guinea pigs were tested for Fetuin-A and PEDF mRNA using RNAscope® technology.ResultsAt 3 min, NKCC1 staining was abolished in the type II fibrocytes in the spiral ligament, followed by a recovery period of up to 120 min. In the stria vascularis, the lowest staining intensity of NKCC1 presented after 30 min. The spiral ganglion showed a stable staining intensity for the full 120 min. Fetuin-A protein and mRNA were detected in the spiral ganglion type I neurons, inner and outer hair cells, pillar cells, Deiters cells and the stria vascularis. Furosemide induced an increased staining intensity of Fetuin-A at 120 min. PEDF protein and mRNA were found in the spiral ganglia type I neurons, the stria vascularis, and in type I and type II fibrocytes of the spiral ligament. PEDF protein staining intensity was high in the pillar cells in the organ of Corti. Furosemide induced an increased staining intensity of PEDF in type I neurons and pillar cells after 120 min.ConclusionThe results indicate rapid furosemide-induced changes of NKCC1 in the type II fibrocytes. This could be part of the mechanism that causes reduction of the EP within minutes after high dose furosemide injection. Fetuin-A and PEDF are present in many cells of the cochlea and probably increase after furosemide exposure, possibly as an otoprotective response.