Sex Differences in Associations of Adiposity Measures and Insulin Resistance in US Hispanic/Latino Youth: The Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth)

Context: US Hispanic/Latino youth are disproportionally affected by the obesity and diabetes. Objective: We examined associations of adiposity measures with insulin resistance (IR) and hyperglycemia and the influences of sex and pubertal development on these associations. Design, Setting, and Participants: We performed a cross-sectional analysis of 1223 8- to 16-year-old Hispanic/Latino youth from a community-based study in the United States (SOL Youth). Main Outcome Measures: We measured IR (≥75th percentile of sex-specific Homeostatic Model Assessment of Insulin Resistance) and hyperglycemia (fasting glucose ≥100 mg/dL or hemoglobin a1c ≥5.7%). Results: In boys, body mass index (BMI) showed the strongest association with IR [prevalence ratio (PR), 2.10; 95% confidence interval (CI), 1.87 to 2.36 per standard deviation], which was not statistically different compared with body fat percentage (%BF) (PR, 2.03; 95% CI, 1.81 to 2.29) and waist circumference (WC) (PR, 1.89; 95% CI, 1.67 to 2.13) but was significantly stronger compared with fat mass index (FMI) (PR, 1.79; 95% CI, 1.63 to 1.96), waist-to-hip ratio (WHR) (PR, 1.32; 95% CI, 1.21 to 1.44), and waist-to-height ratio (WHtR) (PR, 1.76; 95% CI, 1.54 to 2.01) (P for difference, <0.05). In girls, %BF (PR, 2.73; 95% CI, 2.34 to 3.20) showed a significantly stronger association with IR compared with BMI (PR, 1.48; 95% CI, 1.29 to 1.70), FMI (PR, 1.71; 95% CI, 1.49 to 1.95), WC (PR, 1.96; 95% CI, 1.70 to 2.27), WHR (PR, 1.95; 95% CI, 1.70 to 2.23), and WHtR (PR, 1.79; 95% CI, 1.53 to 2.09) (P for difference, <0.003). Associations between adiposity measures and IR were generally stronger among children in puberty versus those who had completed puberty, with significant interactions for WC and WHtR in boys and for BMI in girls (P for interaction, <0.01). Adiposity measures were modestly associated with hyperglycemia (PR, 1.14 to 1.25), with no interactions with sex or pubertal status. Conclusions: Sex and puberty may influence associations between adiposity measures and IR in US Hispanic/Latino youth. Multiple adiposity measures are needed to better assess IR risk between boys and girls according to pubertal status

Do radioiodine-avid lymph nodes from differentiated thyroid cancer on the initial posttherapy scan need repeated 131I therapy?

BackgroundResidual/recurrent lymph node metastase (LNM) is often found after differentiated thyroid cancer (DTC) surgery. This study aimed to investigate whether patients complicated with radioiodine-avid (131I+) lymph nodes from DTC on the initial posttherapy scan (PTS) need repeated 131I therapy.MethodsFrom June 2013 to August 2022, DTC patients with 131I+ lymph nodes on the initial PTS who received at least two cycles of 131I therapy were retrospectively enrolled. They were divided into a complete response (CR) group and an incomplete response (IR) group according to their response to the initial 131I therapy based on the 2015 American Thyroid Association (ATA) guidelines.ResultsA total of 170 DTC patients with 131I+ lymph nodes on the initial PTS were included; 42/170 (24.7%) patients were classified into the CR group and 128/170 (75.9%) were classified into the IR group according to their response to the initial 131I therapy. None of the 42 CR patients had disease progression at the subsequent follow-up, and 37/170 (21.8%) IR patients improved after repeated therapy. Univariate analysis showed that N stage (P=0.002), stimulated thyroglobulin (sTg) level before initial 131I therapy (P&lt;0.001), LNM size (P&lt;0.001), number of total residual/recurrent LNM (P=0.021), radioiodine-nonavid (131I-) LNM (P=0.002) and ultrasound features (P&lt;0.001) were related to the initial treatment response. On multivariate analysis, sTg level (OR=1.186, P&lt;0.001) and LNM size (OR=1.533, P=0.004) were independent risk factors for IR after initial 131I therapy. The optimal sTg level and LNM size cutoff value for predicting the treatment response after initial 131I therapy were 18.2 µg/l and 5mm.ConclusionThis study suggested that approximately one-quarter of patients with 131I+ lymph nodes on initial PTS, especially those with N0 or N1a stage, lower sTg level, smaller LNM size, ≤2 residual/recurrent LNMs, negative ultrasound features and no 131I- LNM, remain stable after one cycle of 131I therapy and do not need repeated therapy

GPI-Based Secrecy Rate Maximization Beamforming Scheme for Wireless Transmission With AN-Aided Directional Modulation

In a directional modulation network, a general power iterative (GPI) based beamforming scheme is proposed to maximize the secrecy rate (SR), where there are two optimization variables required to be optimized. The ?rst one is the useful precoding vector of transmitting con?dential messages to the desired user while the second one is the arti?cial noise (AN) projection matrix of forcing more AN to eavesdroppers. In such a secure network, the paramount problem is how to design or optimize the two optimization variables by different criteria. To maximize the SR (Max-SR), an alternatively iterative structure (AIS) is established between the AN projection matrix and the precoding vector for con?dential messages. To choose a good initial value of iteration process of GPI, the proposed Max-SR method can readily double its convergence speed compared to the random choice of initial value. With only four iterations, it may rapidly converge to its rate ceil. From simulation results, it follows that the SR performance of the proposed AIS of GPI-based Max-SR is much better than those of conventional leakage-based and null-space projection methods in the medium and large signal-to-noise ratio (SNR) regions, and its achievable SR performance gain gradually increases as SNR increases

Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system

AimThe aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database.MethodsAll data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI &gt;1, based on at least 3 reports.ResultsTotal of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (&gt;65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)].ConclusionThis study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe