bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study
Authors: Wu Xueyan , Wang Shuangyuan , Lin Lin , Jia Xiaojing , Hu Chunyan , Qi Hongyan , Lin Hong , Zheng Ruizhi , Li Mian , Xu Yu , Xu Min , Chen Lulu , Zeng Tianshu , Hu Ruying , Ye Zhen , Shi Lixin , Su Qing , Yu Xuefeng , Yan Li , Wang Tiange , Zhao Zhiyun , Zheng Jie , Qin Guijun , Wan Qin , Chen Gang , Dai Meng , Tang Xulei , Gao Zhengnan , Shen Feixia , Gu Xuejiang , Luo Zuojie , Qin Yingfen , Chen Li , Hou Xinguo , Huo Yanan , Li Qiang , Wang Guixia , Zhang Yinfei , Liu Chao , Wang Youmin , Wu Shengli , Yang Tao , Deng Huacong , Zhao Jiajun , Mu Yiming , Ning Guang , Wang Weiqing , Bi Yufang , Chen Yuhong , Lu Jieli 
Published: June 2024

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.
Mendelian randomization unraveled: gender-specific insights into obesity-related phenotypes and colorectal cancer susceptibility
Authors: Chen Xinyi , Yang Mu , Zhao Weiheng , Tu Jingyao , Liu Qingxu , Yuan Xianglin 
Published: June 2024

ObjectiveEvidence has been increasingly pointing towards a potential link between phenotypes related to obesity and the incidence of colorectal cancer. However, confirming this as a direct causal connection remains elusive. This investigation aims to elucidate the causative links between obesity-associated phenotypes and the incidence of colorectal cancer.MethodsEmploying the Two Sample Mendelian Randomization (TwoSampleMR) R package, analyses were conducted using Mendelian randomization (MR) to discern potential causative links between obesity categories sourced from both the Institute for Education and University (IEU) Open GWAS Project and Zenodo, and colorectal tumors (data obtained from IEU Open GWAS and FinnGen). For primary evaluations, the study utilized the Wald ratio and the Inverse Variance Weighting (IVW) methods, while the MR-Egger approach was integrated for sensitivity assessment. Bidirectional Mendelian Randomization (Bidirectional MR), as well as Linkage Disequilibrium (LD) Score Regression with well-imputed HapMap3 single nucleotide polymorphisms (SNPs), were additionally executed. Sensitivity assessments entailed IVW, MR-Egger methodologies to assess heterogeneity and pleiotropy, along with a leave-one-out strategy. Instrumental variables were chosen judiciously based on predetermined P-value thresholds and F-statistics.ResultsResults from MR evaluations did not identify a clear causative link between BMI and colorectal malignancy. Conversely, both measures of obesity, the Waist-Hip Ratio (WHR) and its adjusted form for BMI (WHRadjBMI), displayed a connection to increased risk of colorectal cancer, especially prominent among female subjects. Reverse MR analyses dismissed potential reverse causality between colorectal malignancies and obesity. A significant genetic interplay was observed between WHR, WHRadjBMI, and colorectal cancer instances. Ensuing MR probes spotlighted inflammatory bowel ailment as a protective factor, while salad intake was indicated as a potential risk concerning colorectal malignancies. Sensitivity reviews, which included tests for both pleiotropy and heterogeneity, validated the robustness of the MR findings.ConclusionFindings from this research indicate that specific obesity-related parameters, notably WHR and WHRadjBMI, carry a causal relationship with an elevated colorectal cancer risk. The impact is distinctly more evident among females. Such insights might be pivotal for public health deliberations, hinting that individuals boasting a high WHR might necessitate intensified colorectal cancer screenings.
The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge
Authors: Beltrão Daniele Carvalhal de Almeida , Beltrão Fabyan Esberard de Lima , Carvalhal Giulia , Beltrão Fabyanna Lethicia de Lima , Brito Amanda da Silva , Silva Hatilla dos Santos , Teixeira Helena Mariana Pitangueira , Rodrigues Juliana Lopes , de Figueiredo Camila Alexandrina Viana , Costa Ryan dos Santos , Pordeus Liana Clebia De Morais , Vieira Giciane Carvalho , Ramos Helton Estrela 
Published: June 2024

BackgroundThe Thr92Ala-DIO2 polymorphism has been associated with clinical outcomes in hospitalized patients with COVID-19 and neuropsychiatric diseases. This study examines the impact of the Thr92Ala-DIO2 polymorphism on neuropsychological symptoms, particularly depressive symptoms, in patients who have had moderate to severe SARS-CoV-2 infection and were later discharged.MethodsOur prospective cohort study, conducted from June to August 2020, collected data from 273 patients hospitalized with COVID-19. This included thyroid function tests, inflammatory markers, hematologic indices, and genotyping of the Thr92Ala-DIO2 polymorphism. Post-discharge, we followed up with 68 patients over 30 to 45 days, dividing them into depressive (29 patients) and non-depressive (39 patients) groups based on their Beck Depression Inventory scores.ResultsWe categorized 68 patients into three groups based on their genotypes: Thr/Thr (22 patients), Thr/Ala (41 patients), and Ala/Ala (5 patients). Depressive symptoms were less frequent in the Thr/Ala group (29.3%) compared to the Thr/Thr (59.1%) and Ala/Ala (60%) groups (p = 0.048). The Thr/Ala heterozygous genotype correlated with a lower risk of post-COVID-19 depression, as shown by univariate and multivariate logistic regression analyses. These analyses, adjusted for various factors, indicated a 70% to 81% reduction in risk.ConclusionOur findings appear to be the first to show that heterozygosity for Thr92Ala-DIO2 in patients with COVID-19 may protect against post-COVID-19 depression symptoms up to 2 months after the illness.
A mendelian randomization study revealing that metabolic syndrome is causally related to renal failure
Authors: Cai Xianfu , Wang Decai , Wang Jianjun , Ding Chenguang , Li Yang , Zheng Jin , Xue Wujun 
Published: June 2024

BackgroundThe onset and progression of chronic kidney disease (CKD) has been linked to metabolic syndrome (MetS), with the results of recent observational studies supporting a potential link between renal failure and MetS. The causal nature of this relationship, however, remains uncertain. This study thus leveraged a Mendelian Randomization (MR) approach to probe the causal link of MetS with renal failure.MethodsA genetic database was initially used to identify SNPs associated with MetS and components thereof, after which causality was evaluated through the inverse variance weighted (IVW), MR-Egger regression, and weighted media techniques. Results were subsequently validated through sensitivity analyses.ResultsIVW (OR = 1.48, 95% CI = 1.21–1.82, P =1.60E−04) and weighted median (OR = 1.58, 95% CI =1.15–2.17, P = 4.64E-03) analyses revealed that MetS was linked to an elevated risk of renal failure. When evaluating the specific components of MetS, waist circumference was found to be causally related to renal failure using the IVW (OR= 1.58, 95% CI = 1.39–1.81, P = 1.74e-11), MR-Egger (OR= 1.54, 95% CI = 1.03–2.29, P = 0.036), and weighted median (OR= 1.82, 95% CI = 1.48–2.24, P = 1.17e-8). The IVW method also revealed a causal association of hypertension with renal failure (OR= 1.95, 95% CI = 1.34–2.86, P = 5.42e-04), while renal failure was not causally related to fasting blood glucose, triglyceride levels, or HDL-C levels.ConclusionThese data offer further support for the existence of a causal association of MetS with kidney failure. It is thus vital that MetS be effectively managed in patients with CKD in clinical settings, particularly for patients with hypertension or a high waist circumference who are obese. Adequate interventions in these patient populations have the potential to prevent or delay the development of renal failure.
Association of oxidative balance score with chronic kidney disease: NHANES 1999-2018
Authors: Wen Haibin , Li Xianhua , Chen Jiangming , Li Yi , Yang Nailong , Tan Ning 
Published: June 2024

BackgroundThe Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative stress’s significant role in Chronic Kidney Disease (CKD). This study aims to determine the association between OBS and CKD using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. OBS was constructed from a detailed array of 20 factors, including dietary nutrients and lifestyle behaviors. The relationship between OBS and CKD risk was evaluated using weighted logistic regression models, adjusted for potential confounders, with a generalized additive model (GAM) examining non-linear associations. Subgroup analyses and interaction effects across diverse demographic and clinical groups, along with sensitivity analyses, were performed to validate the findings.ResultsAmong 32,120 participants analyzed, 4,786 were identified with CKD. Fully adjusted weighted logistic regression analysis revealed that each unit increase in OBS was associated with a 2% reduction in CKD prevalence [OR: 0.98 (0.98–0.99), P &lt; 0.001]. Higher OBS quartiles were significantly correlated with a decreased CKD risk [Q4 vs. Q1: OR: 0.82 (0.68–0.98), P = 0.03; P for trend = 0.01]. The GAM and smoothed curve fit indicated a linear relationship between OBS and the risk of CKD. Stratified and sensitivity analyses further substantiated the inverse relationship between OBS and CKD prevalence.ConclusionsOur findings from the NHANES data affirm a significant inverse association between OBS and CKD risk in the U.S. population, underscoring the role of optimizing dietary and lifestyle factors in managing CKD risk. These results advocate for incorporating OBS considerations into CKD prevention and treatment strategies.
HPR1000 pressurizer degassing system design and analysis
Authors: Cui Huaiming , Cai Zhiyun 
Published: June 2024

In the Hualong-1 Unit (HPR1000), the hydrogen (H2) concentration should be reduced to 15 mL (STP)/kg 24 h before reactor shutdown when the reactor vessel is scheduled to be opened. The traditional degassing method, i.e., letting down the reactor coolant through a chemical and volume control system, will take longer, and its operation is more complicated. To shorten the degassing time and simplify the operation, this paper proposes a pressurizer degassing system design for HPR1000 by applying the pressurizer as thermal degassing equipment. Then, the degassing system optimization analysis is carried out under a full range of steady operating conditions during shutdown, and the optimal size of the flow-limiting orifice plate is obtained. Meanwhile, in order to verify the transient characteristic during the degassing process to ensure operating safety, a dedicated transient degassing program based on an improved non-equilibrium multi-region pressurizer model and a transient degassing model is used to carry out a transient simulation analysis of this process. The transient simulation results show that, under bounding conditions of hot–zero-power operation, during the degassing process, the pressure of the pressurizer decreases by a maximum of 0.038 MPa and the water level increases by 0.016 m above the normal level. As can be seen, both the pressure and water level are within the normal operation band and shall not initiate any safety signal. Meanwhile, the entire transient process lasts approximately 24 min and then enters a stable degassing period. It takes approximately 5.2 h to remove the gas dissolved in the reactor coolant from 35 mL (STP)/kg to 15 mL (STP)/kg. The analysis shows that the pressurizer degassing system designed for HPR1000 is safe, effective, and reliable.
The performance evaluation of NIPT for fetal chromosome microdeletion/microduplication detection: a retrospective analysis of 68,588 Chinese cases
Authors: Shen Shichun , Qi Haimei , Yuan Xianping , Gan Jinhui , Chen Junkun , Huang Jungao 
Published: June 2024

BackgroundChromosomal abnormalities are the main cause of birth defects in newborns. Since the inception of noninvasive prenatal testing (NIPT) technology, it has primarily been applied to the detection of common trisomy (T21, T18, T13). However, the application of NIPT in microdeletion and microduplication detection is still controversial.MethodsThis study retrospectively analyzed the data of 68,588 cases that underwent NIPT at Ganzhou Maternal and Child Health Hospital in China. These data were used to evaluate the performance of NIPT in fetal chromosome microdeletion/microduplication detection and to investigate the key factors affecting the NIPT performance.ResultsA total of 281 cases (0.41%) had positive NIPT results with copy number variants (CNVs), of which 161 were validated by karyotyping and chromosome microarray analysis (CMA). Among the 161 cases, 92 were confirmed as true positives through karyotyping or CMA, including 61 microdeletion cases and 31 microduplication cases, resulting in a positive predictive value (PPV) of 57.14%. Improvements in library construction methods increased the fraction of cell-free fetal DNA (cffDNA) from 13.76% to 18.44%, leading to a significant improvement in the detection rate (0.47% vs. 0.15%) and PPV (59.86% vs. 28.57%) of NIPT for CNVs.ConclusionThis study proved the robust performance of NIPT for fetal chromosome microdeletion/microduplication detection. In addition, the cffDNA fraction is a key factor influencing NIPT, with increased cffDNA fraction improving the performance of NIPT.
Deletion of an immune evasion gene, steD, from a live Salmonella enterica serovar Typhimurium vaccine improves vaccine responses in aged mice
Authors: Allen Jessica C. , Natta Shanaliz S. , Nasrin Shamima , Toapanta Franklin R. , Tennant Sharon M. 
Published: June 2024

IntroductionNon-typhoidal Salmonella (NTS) generally causes self-limiting gastroenteritis. However, older adults (≥65 years) can experience more severe outcomes from NTS infection. We have previously shown that a live attenuated S. Typhimurium vaccine, CVD 1926 (I77 ΔguaBA ΔclpP ΔpipA ΔhtrA), was immunogenic in adult but not aged mice. Here we describe modification of CVD 1926 through deletion of steD, a Salmonella effector responsible for host immune escape, which we hypothesized would increase immunogenicity in aged mice.MethodsMel Juso and/or mutuDC cells were infected with S. Typhimurium I77, CVD 1926, and their respective steD mutants, and the MHC-II levels were evaluated. Aged (18-month-old) C57BL/6 mice received two doses of PBS, CVD 1926, or CVD 1926 ΔsteD perorally (109 CFU) and the number of FliC-specific CD4+ T cells were determined. Lastly, aged C57BL/6 mice received three doses of PBS, CVD 1926, or CVD 1926 ΔsteD perorally (109 CFU) and then were challenged perorally with wild-type S. Typhimurium SL1344 (108 CFU). These animals were also evaluated for antibody responses.ResultsMHC-II induction was higher in cells treated with steD mutants, compared to their respective parental strains. Compared to PBS-vaccinated mice, CVD 1926 ΔsteD elicited significantly more FliC-specific CD4+ T cells in the Peyer’s Patches. There were no significant differences in FliC-specific CD4+ T cells in the Peyer’s patches or spleen of CVD 1926- versus PBS-immunized mice. CVD 1926 and CVD 1926 ΔsteD induced similar serum and fecal anti-core and O polysaccharide antibody titers after three doses. After two immunizations, the proportion of seroconverters for CVD 1926 ΔsteD was 83% (10/12) compared to 42% (5/12) for CVD 1926. Compared to PBS-immunized mice, mice immunized with CVD 1926 ΔsteD had significantly lower S. Typhimurium counts in the spleen, cecum, and small intestine upon challenge. In contrast, there were no differences in bacterial loads in the tissues of PBS-vaccinated and CVD 1926-immunized animals.ConclusionThese data suggest that the steD deletion enhanced the immunogenicity of our live attenuated S. Typhimurium vaccine. Deletion of immune evasion genes could be a potential strategy to improve the immunogenicity of live attenuated vaccines in older adults.
Escalating SARS-CoV-2 specific humoral immune response in rheumatoid arthritis patients and healthy controls
Authors: Nemeth Dora , Vago Hajnalka , Tothfalusi Laszlo , Ulakcsai Zsuzsanna , Becker David , Szabo Zsofia , Rojkovich Bernadett , Gunkl-Toth Lilla , Merkely Bela , Nagy Gyorgy 
Published: June 2024

BackgroundImmunocompromised patients are at particular risk of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and previous findings suggest that the infection or vaccination induced immune response decreases over time. Our main goal was to investigate the SARS-CoV-2-specific immune response in rheumatoid arthritis patients and healthy controls over prolonged time.MethodsThe SARS-CoV-2-specific humoral immune response was measured by Elecsys Anti-SARS-CoV-2 Spike (S) immunoassay, and antibodies against SARS-CoV-2 nucleocapsid protein (NCP) were also evaluated by Euroimmun enzyme-linked immunosorbent assay (ELISA) test. The SARS-CoV-2-specific T-cell response was detected by an IFN- γ release assay.ResultsWe prospectively enrolled 84 patients diagnosed with rheumatoid arthritis (RA) and 43 healthy controls in our longitudinal study. Our findings demonstrate that RA patients had significantly lower anti-S antibody response and reduced SARS-CoV-2-specific T-cell response compared to healthy controls (p&lt;0.01 for healthy controls, p&lt;0.001 for RA patients). Furthermore, our results present evidence of a notable increase in the SARS-CoV-2-specific humoral immune response during the follow-up period in both study groups (p&lt;0.05 for healthy volunteers, p&lt;0.0001 for RA patients, rank-sum test). Participants who were vaccinated against Coronavirus disease-19 (COVID-19) during the interim period had 2.72 (CI 95%: 1.25–5.95, p&lt;0.05) times higher anti-S levels compared to those who were not vaccinated during this period. Additionally, individuals with a confirmed SARS-CoV-2 infection exhibited 2.1 times higher (CI 95%: 1.31–3.37, p&lt;0.01) anti-S levels compared to those who were not infected during the interim period. It is worth noting that patients treated with targeted therapy had 52% (CI 95%: 0.25–0.94, p&lt;0.05) lower anti-S levels compared to matched patients who did not receive targeted therapy. Concerning the SARS-CoV-2-specific T-cell response, our findings revealed that its level had not changed substantially in the study groups.ConclusionOur present data revealed that the level of SARS-CoV-2-specific humoral immune response is actually higher, and the SARS-CoV-2-specific T-cell response remained at the same level over time in both study groups. This heightened humoral response, the nearly permanent SARS-CoV-2-specific T-cell response and the coexistence of different SARS-CoV-2 variants within the population, might be contributing to the decline in severe COVID-19 cases.
Consuming royal jelly alters several phenotypes associated with overwintering dormancy in mosquitoes
Authors: Bianco Olivia E. , Abdi Aisha , Klein Matthias S. , Wei Xueyan , Sim Cheolho , Meuti Megan E. 
Published: June 2024

IntroductionFemales of the Northern house mosquito, Culex pipiens, enter an overwintering dormancy, or diapause, in response to short day lengths and low environmental temperatures that is characterized by small egg follicles and high starvation resistance. During diapause, Culex pipiens Major Royal Jelly Protein 1 ortholog (CpMRJP1) is upregulated in females of Cx. pipiens. This protein is highly abundant in royal jelly, a substance produced by honey bees (Apis mellifera), that is fed to future queens throughout larval development and induces the queen phenotype (e.g., high reproductive activity and longer lifespan). However, the role of CpMRJP1 in Cx. pipiens is unknown.MethodsWe first conducted a phylogenetic analysis to determine how the sequence of CpMRJP1 compares with other species. We then investigated how supplementing the diets of both diapausing and nondiapausing females of Cx. pipiens with royal jelly affects egg follicle length, fat content, protein content, starvation resistance, and metabolic profile.ResultsWe found that feeding royal jelly to females reared in long-day, diapause-averting conditions significantly reduced the egg follicle lengths and switched their metabolic profiles to be similar to diapausing females. In contrast, feeding royal jelly to females reared in short-day, diapause-inducing conditions significantly reduced lifespan and switched their metabolic profile to be similar nondiapausing mosquitoes. Moreover, RNAi directed against CpMRJPI significantly increased egg follicle length of short-day reared females, suggesting that these females averted diapause.DiscussionTaken together, our data show that consuming royal jelly reverses several key seasonal phenotypes of Cx. pipiens and that these responses are likely mediated in part by CpMRJP1.