Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.

Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Association between urinary polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion from a case-control study.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to be associated with adverse pregnancy outcomes. However, there is limited knowledge regarding the effects of single or mixed PAHs exposure on unexplained recurrent spontaneous abortion (URSA). This study aimed to investigate the association between monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and URSA in a case-control study. The results showed that 1-NAP, 2-NAP, 9-FLU, and 1-PYR were detected in 100% of the subjects among measured all sixteen OH-PAHs. Compared with those in the lowest quartiles, participants in the highest quartiles of 3-BAA were associated with a higher risk of URSA (OR (95%CI) = 3.56(1.28-9.85)). With each one-unit increase of ln-transformed 3-BAA, the odds of URSA increased by 41% (OR (95%CI) = 1.41(1.05-1.89)). Other OH-PAHs showed negative or non-significant associations with URSA. Weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp) analyses consistently identified 3-BAA as the major contributor to the mixture effect of OH-PAHs on URSA. Our findings suggest that exposure to 3-BAA may be a potential risk factor for URSA. However, further prospective studies are needed to validate our findings in the future.

Association of urinary nickel levels with diabetes and fasting blood glucose levels: A nationwide Chinese population-based study.

Some epidemiological studies support a relationship between nickel exposure and diabetes in the general population. To address this, we tested the association of nickel exposure with diabetes in 10,890 adults aged ≥ 18 years old from the China National Human Biomonitoring study conducted in 2017-2018. Urinary nickel concentrations and fasting blood glucose (FBG) were measured, and lifestyle and demographic data were collected. Weighted logistic and linear regressions were used to estimate the associations of urinary nickel levels with diabetes prevalence and FBG. Restricted cubic splines (RCS) were used to test for the dose-response relationship. The odd ratio (95% confidence interval [CI]) of diabetes for the highest versus lowest quartiles of urinary nickel concentrations was 1.74 (1.28, 2.36) in the multivariate model (p trend =0.001). Each one-unit increase in log-transformed urinary nickel concentrations was associated with a 0.36 (0.17, 0.55) mmol/L elevation in FBG. The RCS curves showed a monotonically increasing dose-response relationship of urinary nickel with diabetes as well as FBG levels, and then tended to flatten after about 4.75 µg/L of nickel exposure. The nickel-diabetes association was stronger in individuals with lower than those with higher rice consumption (OR: 2.39 vs. 1.72). Our study supports a positive association between nickel exposure and diabetes prevalence in Chinese adults, especially in individuals with lower rice consumption. Further large-scale prospective studies are needed to validate our findings.

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas.

OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.

MetaGSCA: A tool for meta-analysis of gene set differential coexpression.

Analyses of gene set differential coexpression may shed light on molecular mechanisms underlying phenotypes and diseases. However, differential coexpression analyses of conceptually similar individual studies are often inconsistent and underpowered to provide definitive results. Researchers can greatly benefit from an open-source application facilitating the aggregation of evidence of differential coexpression across studies and the estimation of more robust common effects. We developed Meta Gene Set Coexpression Analysis (MetaGSCA), an analytical tool to systematically assess differential coexpression of an a priori defined gene set by aggregating evidence across studies to provide a definitive result. In the kernel, a nonparametric approach that accounts for the gene-gene correlation structure is used to test whether the gene set is differentially coexpressed between two comparative conditions, from which a permutation test p-statistic is computed for each individual study. A meta-analysis is then performed to combine individual study results with one of two options: a random-intercept logistic regression model or the inverse variance method. We demonstrated MetaGSCA in case studies investigating two human diseases and identified pathways highly relevant to each disease across studies. We further applied MetaGSCA in a pan-cancer analysis with hundreds of major cellular pathways in 11 cancer types. The results indicated that a majority of the pathways identified were dysregulated in the pan-cancer scenario, many of which have been previously reported in the cancer literature. Our analysis with randomly generated gene sets showed excellent specificity, indicating that the significant pathways/gene sets identified by MetaGSCA are unlikely false positives. MetaGSCA is a user-friendly tool implemented in both forms of a Web-based application and an R package "MetaGSCA". It enables comprehensive meta-analyses of gene set differential coexpression data, with an optional module of post hoc pathway crosstalk network analysis to identify and visualize pathways having similar coexpression profiles.

Prognostic Clinical and Radiographic Biomarkers for BRAF-Targeted Therapy in Advanced Melanoma.

Agents blocking BRAF and MEK produce robust responses in patients with BRAFV600 -mutated melanoma; however, more accurate clinical biomarkers are needed to predict prognosis. To explore this question, we retrospectively studied 158 patients with BRAF-mutated melanoma treated with BRAF with or without MEK inhibitors. We found that the number of distinct tumor sites upon initiation of targeted therapy was associated with decreased progression-free survival but had no effect on overall survival. Serum values of lactate dehydrogenase and absolute lymphocyte count to absolute neutrophil count ratio independently had the strongest association with both progression-free survival and overall survival. Using both of these markers can help stratify prognosis of patients with metastatic melanoma receiving targeted therapy.

Outcomes after progression of disease with anti-PD-1/PD-L1 therapy for patients with advanced melanoma.

BACKGROUND: Greater than one-half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti-PD-1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti-PD-1 therapy. METHODS: The authors evaluated 383 consecutively treated patients who received anti-PD-1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival were assessed. RESULTS: Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%). CONCLUSIONS: The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.

Current Perceptions of the Aesthetically Ideal Position and Size of the Male Nipple-Areola Complex.

BACKGROUND: The dimensions of the nipple-areola complex (NAC) and its location on the chest wall are important aesthetic factors in male breast surgery. OBJECTIVES: This study examines the perceptions of aesthetic surgeons and the general population for the aesthetically ideal position and size of male NAC. METHODS: An online survey was distributed to the American Society for Aesthetic Plastic Surgery (ASAPS) members and to the general population. Parameters queried included demographics for all participants and academic details for ASAPS members. Both surveys included a male model picture with 16 separate choices for the NAC position from a frontal view, 5 choices for the NAC position from a lateral view, and 6 choices for the NAC dimensions. For all 3 sets of images, the participants were asked to rank the top 3 images they considered most "aesthetically pleasing" in descending order. A weighted scoring rule was created to quantitatively evaluate image choices. Standard statistical methods were employed for analysis. RESULTS: The survey was completed by 272 ASAPS members and 4909 participants from the general population. The top 3 choices for NAC location on frontal view were the same for ASAPS members and the general population. The most popular NAC location on lateral view was the same for both groups, but the preferred locations differed between the 2 groups for the second and third choices. The most popular dimensions of the NAC were 2 cm (vertical) × 3 cm (horizontal) followed by 2 cm × 2 cm for both groups. Comparison of the 3 top image choices scores between different ethnic groups and individuals with different gender or sexual orientation demonstrated similar trends. CONCLUSIONS: This survey identified the preferred position and dimensions of the NAC on the male breast for plastic surgeons and the general population. These parameters should be considered when counseling males undergoing breast surgery.