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Background: Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States. Methods: 6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001–2018) were included in this study. The mortality status of the follow-up was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. We used cox proportional hazards models to estimate the association of serum 25(OH)D concentrations and mortality of postmenopausal females. Results: The mean level of serum 25(OH)D was 72.57 ± 29.93 nmol/L, and 65.34% had insufficient vitamin D. In postmenopausal females, low serum 25(OH)D concentrations were significantly associated with higher levels of glycohemoglobin, glucose, and lower levels of HDL. During follow-up, 1448 all-cause deaths occurred, including 393 cardiovascular disease (CVD)-related deaths and 263 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly related with lower all-cause and CVD mortality. In addition, serum 25(OH)D presented a L-shaped relationship with all-cause mortality, while appeared a U-shaped with CVD mortality, and the cut-off value is 73.89 nmol/L and 46.75 nmol/L respectively. Conclusions: Low serum 25(OH)D levels are associated with the higher risk of all-cause and CVD mortality in postmenopausal females. These findings provide new ideas and targets for the health management of postmenopausal women. [ABSTRACT FROM AUTHOR]

Olivine polymorphs are considered the most abundant minerals in Earth and vital to governing its dynamics. Seismic discontinuities near 410 and 660 km depth are attributed to phase transitions of olivine polymorphs and have long been in reference Earth models. However, the significance of the 520 km discontinuity (520) and its causative phase transition are debated. To address its prevalence and properties, receiver functions from >2,000 seismographs across the U.S. were inverted using parameterizations with and without the 520. A 520 is required for 84% of the area at 95% confidence. The 520s depths and S‐velocity contrasts nearly match predictions from the pyrolite model, as expected for a widespread feature that dominantly reflects the wadsleyite to ringwoodite transition. Plain Language Summary: Extremely high temperature and high pressure inside Earth's mantle can change the intrinsic structure of minerals, and the transitions between mineral structures can act as interfaces that reflect or convert seismic waves. Thus, seismically mapping these interfaces can provide information on the thermal and chemical conditions at inaccessible depths. Here, we combined seismic observations from >2,000 instruments and statistical tools to investigate an often overlooked, and therefore still debated, mantle interface at about 520 km depth within a layer called the mantle transition zone. We found that the prevalence of the 520 km interface is almost universal beneath the contiguous United States. Additionally, the average seismic properties of the interface are consistent with predictions for an olivine‐rich model of upper mantle composition referred to as pyrolite. Our findings indicate that the average composition within the mantle transition zone is similar to the shallower upper mantle under most places in United States. Regional deviations from the mean interface depth can be explained by plausible temperature variations based on laboratory mineral physics predictions. Our study shows that where adequate seismic data exists, the 520 km interface can serve as a valuable marker of mantle temperature and composition. Key Points: Simultaneously fitting spatially stacked receiver functions in several frequency bands improves detection of the 520 km discontinuityF‐test results indicate a widespread 520 km discontinuity beneath the contiguous United StatesThe mean depth (506 km) and Vs contrast (1.9%) are consistent with predictions for a pyrolite composition and a normal mantle geotherm [ABSTRACT FROM AUTHOR]

More than one-quarter of the adults living with diagnosed HIV infection in the US are women. Binge drinking (i.e., ≥4 alcoholic drinks per occasion for women) is associated with poor HIV treatment compliance, HIV incidence, and unplanned pregnancy. However, little is known about the prevalence of binge drinking among women of childbearing age who are living with HIV (WLWH) and health risk behaviours among those who binge drink. Using the 2013–2014 data cycles of Medical Monitoring Project, we assessed the weighted prevalence of drinking patterns by socio-demographic, clinical and reproductive characteristics of 946 WLWH. Logistic regression was used to calculate unadjusted and adjusted prevalence ratios and 95% confidence intervals. Overall, 39% of WLWH reported current drinking and 10% reported binge drinking. Compared to non-drinkers, binge drinkers were less likely to adhere to antiretroviral therapy (ART) or be virally suppressed. In multivariate analyses, binge drinking among WLWH was associated with smoking, drug use, and reduced ART adherence compared to non-drinkers, increasing the likelihood of negative clinical outcomes. WLWH may benefit from a comprehensive approach to reducing binge drinking including alcohol screening and brief interventions and evidence-based policy strategies that could potentially improve adherence to HIV treatment. [ABSTRACT FROM AUTHOR]

Large scale temporal data have flourished in a vast array of applications, and their sophisticated structures, especially the heteroscedasticity among subjects with inter- and intra-temporal dependence, have fueled a great demand for new statistical models. In this paper, with covariate information, we consider a flexible model for large scale temporal data with subject-specific heteroscedasticity. Formally, the model employs latent semiparametric factors to simultaneously account for the subject-specific heteroscedasticity and the contemporaneous and/or serial correlations. The subject-specific heteroscedasticity is modeled as the product of the unobserved factor process and subject's covariate effect, which is further characterized via additive models. For estimation, we propose a two-step procedure. First, the latent factor process and nonparametric loading are recovered through projection-based methods, and following, we estimate the regression components by approaches motivated from the generalized least squares. By scrupulously examining the non-asymptotic rates for recovering the factor process and its loading, we show the consistency and efficiency of estimated regression coefficients in the absence of prior knowledge of latent factor process and subject's covariate effect. The statistical guarantees remain valid even for finite time points that makes our method particularly appealing when the subjects significantly outnumber the observation time points. Using comprehensive simulations, we demonstrate the finite sample performance of our method, which corroborates the theoretical findings. Finally, we apply our method to a data set of air quality and energy consumption collected at 129 monitoring sites in the United States in 2015. [ABSTRACT FROM AUTHOR]

Introduction: This study examined the association between American Heart Association's (AHA) cardiovascular health (CVH) metrics, Life's Essential 8 (LE8), and predicted heart age among U.S. adults., Methods: The sample comprised 7,075 participants aged 30-74 years without CVD and/or stroke from the National Health and Nutrition Examination Survey (NHANES) 2015-March 2020. LE8 was measured according to AHA's metrics (overall score ranging from 0 to 100 points), and nonlaboratory-based Framingham Risk Score was used to estimate predicted heart age. Analyses were completed in June 2024., Results: Median LE8 scores were 62.8 for men and 66.0 for women. Over 80% of participants had less than optimal CVH scores, affecting 141.5 million people and 1-in-6 participants had a low CVH score, impacting 30.0 million people. Mean predicted heart age and excess heart age (EHA, difference between actual and predicted heart age) were 56.6 (95% CI 56.1-57.1) and 8.6 (8.1-9.1) years for men and 54.0 (53.4-54.7) and 5.9 (5.2-6.5) years for women. Participants in the low CVH group (scores<50), had an EHA that was 20.7 years higher than those in the high CVH group (score 80-100). Compared to the high CVH group, participants in low CVH group had 15 times (for men) and 44 times (for women) higher risk of having EHA ≥10 years. The pattern of differences in predicted heart age, EHA, and prevalence of EHA ≥10 years by LE8 groups remained largely consistent across subpopulations., Conclusions: These findings highlight the importance of maintaining a healthy lifestyle to improve cardiovascular health and reduce excess heart age., (Published by Elsevier Inc.)

Background: The use of correctly sized blood pressure (BP) cuffs is important to ensure accurate measurement and effective management of hypertension. The goals of this study were to determine the proportions of pregnant women that would require small, adult, large, and extra-large (XL) cuff sizes, and to examine the demographic characteristics associated with need for a large or XL cuff., Methods: This cross-sectional study analyzed 1,176 pregnant women (≥18 years) included in the National Health and Nutrition Examination Survey (NHANES) 1999-2006 cycles. Recommended BP cuff sizes, based on American Heart Association recommendations, were categorized by mid-arm circumference: small adult (≤26 cm), adult (>26 to ≤34 cm), large (>34 to ≤44 cm), and extra-large (XL) (>44 cm)., Results: Among US pregnant women, recommended cuff sizes were: 17.9% small adult, 57.0% adult, and 25.1% for large or XL. About 38.5% of non-Hispanic Black, 21.6% of Mexican American and 21.0% of non-Hispanic White pregnant women required a large or XL cuff. About 81.8% of women in the highest quartile for BMI required large or XL cuffs, which was significantly higher than women in other quartiles., Conclusion: Roughly one out of every four pregnant women required large or XL BP cuffs. The requirement for large or XL cuffs was highest among non-Hispanic Black women and women with the highest BMI. For pregnant women, measuring the arm circumference and selecting an appropriately sized cuff is important to facilitate accurate blood pressure monitoring and hypertension management., (© Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2024.)

In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists., Competing Interests: Declaration of competing interest All authors have approved the final submission to the journal. The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Variant-containing mRNA vaccines for COVID-19 to broaden protection against SARS-CoV-2 variants are recommended based on findings in adults. We report interim safety and immunogenicity of an omicron BA.1 variant-containing (mRNA-1273.214) primary vaccination series and booster dose in paediatric populations., Methods: This open-label, two-part, non-randomised phase 3 trial enrolled participants aged 6 months to 5 years at 24 US study sites. Eligible participants were generally healthy or had stable chronic conditions, without known SARS-CoV-2 infection in the previous 90 days. Individuals who were acutely ill or febrile 1 day before or at the screening visit or those who previously received other COVID-19 vaccines (except mRNA-1273 for part 2) were excluded. In part 1, SARS-CoV-2-vaccine-naive participants received two-dose mRNA-1273.214 (25 μg; omicron BA.1 and ancestral Wuhan-Hu-1 mRNA) primary series. In part 2, participants who previously completed the two-dose mRNA-1273 (25 μg) primary series in KidCOVE (NCT04796896) received a mRNA-1273.214 (10 μg) booster dose. Primary study outcomes were safety and reactogenicity of the mRNA-1273.214 primary series (part 1) or booster dose (part 2) as well as the inferred effectiveness of mRNA-1273.214 based on immune responses against ancestral SARS-CoV-2 (D614G) and omicron BA.1 variant at 28 days post-primary series (part 1) or post-booster dose (part 2). The safety set included participants who received at least one dose of the study vaccine; the immunogenicity set included those who provided immunogenicity samples. Interim safety and immunogenicity are summarised in this analysis as of the data cutoff date (Dec 5, 2022). This trial is registered with ClinicalTrials.gov, NCT05436834., Findings: Between June 21, 2022, and Dec 5, 2022, 179 participants received one or more doses of mRNA-1273.214 primary series (part 1) and 539 received a mRNA-1273.214 booster dose (part 2). The safety profile within 28 days after either dose of the mRNA-1273.214 primary series and the booster dose was consistent with that of the mRNA-1273 primary series in this age group, with no new safety concerns or vaccine-related serious adverse events observed. At 28 days after primary series dose 2 and the booster dose, both mRNA-1273.214 primary series (day 57, including all participants with or without evidence of prior SARS-CoV-2 infection at baseline) and booster (day 29, including participants without evidence of prior SARS-CoV-2 infection at baseline) elicited responses that were superior against omicron-BA.1 (geometric mean ratio part 1: 25·4 [95% CI 20·1-32·1] and part 2: 12·5 [11·0-14·3]) and non-inferior against D614G (part 1: 0·8 [0·7-1·0] and part 2: 3·1 [2·8-3·5]), compared with neutralising antibody responses induced by the mRNA-1273 primary series (in a historical comparator group)., Interpretation: mRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a two-dose primary series or a booster dose. These results are aligned with the US Centers for Disease Control and Prevention recommendations for the use of variant-containing vaccines for continued protection against the emerging variants of SARS-CoV-2., Funding: Moderna., Competing Interests: Declaration of interests AD, RP, KH, BG, WZ, WD, HZ, SSG, JMM, FP, and RD are employees of Moderna, and hold stock or stock options in the company. AY, KS, and BJK are consultants for Moderna. BJK is a member of the Children's Hospital of Philadelphia Vaccine Education Center research team and no payments have been received for this study. RB, KA, MT, CG, and RAC declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Self-measured blood pressure monitoring (SMBP) is an important out-of-office resource that is effective in improving hypertension control. Changes in SMBP use during the Coronavirus Disease 2019 (COVID-19) pandemic have not been described previously., Methods: Behavioral Risk Factor Surveillance System (BRFSS) data were used to quantify changes in SMBP use between 2019 (prior COVID-19 pandemic) and 2021 (during the COVID-19 pandemic). Fourteen states administered the SMBP module in both years. All data were self-reported from adults who participated in the BRFSS survey. We assessed the receipt of SMBP recommendations from healthcare professionals and actual use of SMBP among those with hypertension (n = 68,820). Among those who used SMBP, we assessed SMBP use at home and sharing BP readings electronically with healthcare professionals., Results: Among adults with hypertension, there was no significant changes between 2019 and 2021 in those reporting SMBP use (57.0% vs. 55.7%) or receiving recommendations from healthcare professionals to use SMBP (66.4% vs. 66.8%). However, among those who used SMBP, there were significant increases in use at home (87.7% vs. 93.5%) and sharing BP readings electronically (8.6% vs. 13.1%) from 2019 to 2021. Differences were noted by demographic characteristics and residence state., Conclusions: Receiving a recommendation from the healthcare provider to use SMBP and actual use did not differ before and during the COVID-19 pandemic. However, among those who used SMBP, home use and sharing BP readings electronically with healthcare professional increased significantly, although overall sharing remained low (13.1%). Maximizing advances in virtual connections between clinical and community settings should be leveraged for improved hypertension management., (© Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2024.)

The spread of COVID-19 has been greatly impacted by regulatory policies and behavior patterns that vary across counties, states, and countries. Population-level dynamics of COVID-19 can generally be described using a set of ordinary differential equations, but these deterministic equations are insufficient for modeling the observed case rates, which can vary due to local testing and case reporting policies and nonhomogeneous behavior among individuals. To assess the impact of population mobility on the spread of COVID-19, we have developed a novel Bayesian time-varying coefficient state-space model for infectious disease transmission. The foundation of this model is a time-varying coefficient compartment model to recapitulate the dynamics among susceptible, exposed, undetected infectious, detected infectious, undetected removed, hospitalized, detected recovered, and detected deceased individuals. The infectiousness and detection parameters are modeled to vary by time, and the infectiousness component in the model incorporates information on multiple sources of population mobility. Along with this compartment model, a multiplicative process model is introduced to allow for deviation from the deterministic dynamics. We apply this model to observed COVID-19 cases and deaths in several U.S. states and Colorado counties. We find that population mobility measures are highly correlated with transmission rates and can explain complicated temporal variation in infectiousness in these regions. Additionally, the inferred connections between mobility and epidemiological parameters, varying across locations, have revealed the heterogeneous effects of different policies on the dynamics of COVID-19., (© 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer., Objective: We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC)., Design, Setting, and Participants: Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC., Outcome Measurements and Statistical Analysis: Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival., Results and Limitations: Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients., Conclusions: The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management., Patient Summary: The RCClnc4 classifier could facilitate patient management and treatment decisions., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)