Search

The transmission of coronavirus disease‐2019 (COVID‐19) epidemic is a global emergency, which is worsened by the genetic mutations of SARS‐CoV‐2. However, till date, few statistical studies have researched the COVID‐19 spread patterns in terms of the variant cases. Hence, this paper aims to explore the associated risk factors of Delta variant, the most contagious strain of COVID‐19. The study collected the state‐level COVID‐19 Delta variant cases in the United States during a 12‐week period and included potential environmental, socioeconomic, and public prevention factors as independent variables. Instead of regarding the covariate effects as constant, this paper proposes a flexible Bayesian hierarchical model with spatio‐temporally varying coefficients to account for data heterogeneity. The method enables us to cluster the states into distinctive groups based on the temporal trends of the coefficients and simultaneously identify significant risk factors for each cluster. The findings contribute novel insight into the dynamics of covariate effects on the COVID‐19 Delta variant over space and time, which could help the government develop targeted prevention measures for vulnerable regions based on the selected risk factors. [ABSTRACT FROM AUTHOR]

Population attributable risk (PAR) is becoming more widely used for quantifying preventability of cancer. However, its estimations have had a wide range, leading to questions about the true preventability. Our study aimed to compare the two PAR estimation methods (ie, literature‐based method and low‐risk method) for colorectal cancer (CRC) in the US population based on the same set of modifiable risk factors: physical activity, body mass index, alcoholic drinks, red meat, processed meat, dietary fiber, dietary calcium and cigarette smoking. For the literature‐based method, 65% and 53%, and for the low‐risk method, 62% and 49% of CRC cases for males and females, respectively, were attributable to the eight dietary and lifestyle risk factors. Additional sensitivity analyses were conducted with respect to the different choices of risk factors, relative risks (RRs) and exposure prevalence estimates used in the literature‐based method. The PARs including only the "convincing" factors and excluding "probable" factors defined by the WCRF/AICR were 50% for males and 34% for females. Using RRs derived from different studies changed the PARs considerably (57%‐74% for males and 37%‐60% for females). Our study assessed the robustness of PAR calculations through a direct comparison between the two methods using different assumptions and data and generally found high concordance. From the additional analyses, we found that the choice of risk factors and RRs could substantially influence the PAR estimates. Given the findings, future studies reporting PAR should consider presenting a range of PAR estimates based on choices of risk factors and RRs. What's new? Population attributable risk (PAR) is increasingly used for quantifying the preventability of cancer. However, estimations vary widely. This study assessed the robustness of PAR calculations for colorectal cancer in the US population through a direct comparison between the literature‐based method and the low‐risk method using the same risk factors, and generally found high concordance. Additional sensitivity analyses, however, showed that for the literature‐based method, the choice of risk factors and relative risks could substantially influence PAR estimations. Future PAR studies using the literature‐based method should consider presenting a range of estimates from different choices of risk factors and relative risks. [ABSTRACT FROM AUTHOR]

Background: Healthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention.Methods and Findings: We assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses' Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants' mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population.Conclusions: Our study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is the most common urinary system malignancy in the United States and is characterized by its diverse prognosis and high recurrence rate. However, the molecular mechanisms underlying its progression remain unknown. Accumulating evidence suggests a critical role for miRNAs in bladder cancer progression. Methods and results: In this study, we found that miR-492 expression levels were significantly higher in bladder cancer tissue and the serum of bladder cancer patients by bioinformatics analysis and a panel of clinical samples. The results of receiver operating characteristic curve analysis suggested the potential diagnostic value of serum miR-492 for bladder cancer. In vitro and in vivo functional assays showed that knockdown of miR-492 suppressed proliferation and metastasis of bladder cancer cells. Gap junction beta-4 protein was predicted to be a direct target of miR-492, which was validated using a luciferase reporter assay. Further cellular functional assays showed that suppression of miR-492 abrogated bladder cancer cell proliferation and metastasis by targeting gap junction beta-4 protein. Conclusion: miR-492 promotes cancer progression by targeting GJB4 and is a novel biomarker for bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children. Materials and Methods: A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide. Results: Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation. Conclusions: Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations. [ABSTRACT FROM AUTHOR]

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes. [ABSTRACT FROM AUTHOR]

To investigate the relationship between dietary flavonoid intake and depression symptoms in American adults. Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2008, 2009–2010, and 2017–2018 survey cycles. Both males and females aged 18 years and older with complete information about dietary flavonoid intake (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols), depression symptoms, and covariates were included. Logistic regression models were conducted to calculate the odds ratio (OR) of single dietary flavonoid subclass intake on depression, and the restricted cubic spline (RCS) models were utilized to explore the corresponding dose-response relationships. Additionally, we implemented the weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models to estimate the mixed effects of six flavonoid subclasses and identify the predominant types. After multivariable adjustments, people with higher consumption of flavanones (OR: 0.68, 95% CI: 0.52–0.90, p = 0.008), flavones (OR: 0.63, 95% CI: 0.46–0.87, p = 0.007), flavonols (OR: 0.66, 95% CI: 0.49–0.89, p = 0.008), and total flavonoids (OR: 0.69, 95% CI: 0.50–0.95, p = 0.024) had lower odds of depression symptoms. Meanwhile, significant dose-response relationships were supported by the RCS models. However, no obvious associations between isoflavones, anthocyanidins, flavan-3-ols, and the odds of suffering from depression symptoms were found by the logistic regression models and RCS models. As for the mixed effect, the WQS and qgcomp models both demonstrated that the mixture of six flavonoid subclasses was inversely related to the odds ratios of depression symptoms, and flavones, flavanones, and anthocyanidins were the top 3 contributors. Our study implied dietary flavonoid intake was associated with the decreased probability of depression symptoms in U.S. adults, among which flavones, flavanones, and anthocyanidins may occupy the predominant roles. [ABSTRACT FROM AUTHOR]

Future ambient air quality will respond to changes in anthropogenic and biogenic emissions as well as climate changes, which may vary at national and state levels in different regions of the world. In this work, we applied an advanced online-coupled meteorology and chemistry model, the Weather Research and Forecasting Model with Chemistry (WRF/Chem), to the continental U.S. for current (2001-2010) and future (2046-2055) decades under four climate scenarios including the Representative Concentration Pathways (RCP) 4.5 and 8.5 and the Technology Driver Model (TDM) A1B and B2. Our goal is to quantify the impact of projected changes in anthropogenic and biogenic emissions and climate on future air quality under various climate scenarios for policy analysis for emission control and mitigation of adverse climate change. The simulations are performed at 36-, 12-km, and 4-km over North America, Continental U.S., and selected states, respectively. A comprehensive evaluation has been performed for the current simulation period using available observations from surface networks and satellites and shows an overall good performance in reproducing climatic and chemical observations at all grid scales. Future air quality features greater reduction in PM 2.5 by RCP 4.5/8.5 than TDM B2/A1B and decreased O 3 over most areas in the U.S. by RCP4.5 and TDM B2, indicating the benefits of carbon policy and technology changes with greater emission reductions. Air quality responds differently to projected changes in anthropogenic emissions in different states and seasons, indicating a need to develop state-specific emission control strategies for different seasons. [ABSTRACT FROM AUTHOR]

Air pollution from greenhouse gases and atmospheric aerosols are the major driving force of climate change that directly alters the terrestrial hydrological cycle and ecosystem functions. However, most current Global Climate Models (GCMs) use prescribed chemical concentrations of limited species; they do not explicitly simulate the time-varying concentrations of trace gases and aerosols and their impacts on climate change. This study investigates the individual and combined impacts of climate change and air pollution on water availability and ecosystem productivity over the conterminous US (CONUS). An ecohydrological model is driven by multiple regional climate scenarios with and without taking into account the impacts of air pollutants on the climate system. The results indicate that regional chemistry-climate feedbacks may largely offset the future warming and wetting trends predicted by GCMs without considering air pollution at the CONUS scale. Consequently, the interactions of air pollution and climate change are expected to significantly reduce water availability by the middle of twenty-first century. On the other hand, the combined impact of climate change and air pollution on ecosystem productivity is less pronounced, but there may still be notable declines in eastern and central regions. The results suggest that air pollution could aggravate regional climate change impacts on water shortage. We conclude that air pollution plays an important role in affecting climate and thus ecohydrological processes. Overlooking the impact of air pollution may cause evident overestimation of future water availability and ecosystem productivity. [ABSTRACT FROM AUTHOR]

Background. The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF,ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. Methods. CGP was performed to a mean coverage depth of 5763 on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. Results. The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%). Conclusion. CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials. [ABSTRACT FROM AUTHOR]

We find that subsequent to both US and domestic market gains, both Asian individual and insti-tutional investors increase their trading and that this effect is more pronounced in bull markets, in periods of relatively favorable investor sentiment, in periods of extremely high market returns, and in markets with short-sale constraints. We also find that individual investors trade more in response to market gains than institutional investors. Moreover, we find that further integration of Asian stock markets with US stock markets after the Asian financial crisis in 1998 is an important reason for Asian investors ' response to US market gains. [ABSTRACT FROM AUTHOR]

This manuscript is remarkable for revealing a striking difference in the annual mortality rate between patients from Beijing compared to those in the United States.Background The raw annual mortality rate reported in Chinese patients on maintenance hemodialysis (MHD) was around 10% between 2005 to 2010, and it was around 20% in the US as reported by the United States Renal Data System (USRDS). Our hypothesis was that the large survival difference was caused by differences in race and practice pattern between nations in addition to differences in patient characteristics. Methods Annual mortality in Beijing prevalent MHD patients per year in 2007, 2008, 2009 and 2010 was reported and relative risks of death were compared with the corresponding mortality of USRDS prevalent MHD patients (in whites, African-Americans and Asian-Americans) after age, gender and primary cause of end-stage renal disease (ESRD) were adjusted. A total of 11 675 MHD patients from 104 dialysis facilities under control of Beijing Blood Purification Quality Control and Improvement Center (BJBPQCIC) from 31 December 2006 to 31 December 2010 were included. A total of 1 937 819 MHD patients (only white, African-American and Asian-American were eligible for inclusion) were subtracted from the USRDS No-60-Day prevalent dataset from the year 2004 to 2009, using the RenDER system. Raw annual mortality for each race was reported as a number per 1000 MHD patients at risk for each year. Age, gender and primary cause of ESRD, adjusted annual mortality and relative risk race of death were reported comparing the Beijing patients and each race of the USRDS. Results The raw annual mortality for the Beijing cohort increased gradually from 47.8 per 1000 patient-years in 2007 to 76.8 in 2010. The raw annual mortality for the white cohort in 2007 was 250.7 per 1000 patient-years, and gradually decreased to 236.3 in 2009. The raw annual mortality for African-Americans (167.8 and 156.7 per 1000 patient-years in 2007 and 2009, respectively) was much lower than that for whites. The annual mortality for Asian-Americans was slightly lower than that for African-Americans. After adjustment, Beijing MHD still had a survival benefit compared with each of the examined USRDS race. The annual mortality rates were 99.4, 80.6 and 94.3 per 1000 patient-years when adjusted to whites, African-Americans and Asian-Americans, respectively, in cohort 2009. Conclusions The annual mortality for the Beijing MHD patients was lower than that for their USRDS counterparts, and this difference existed after baseline demographics were adjusted. This survival difference between the Beijing and the USRDS MHD cohorts could be attributed to differences in race or practice pattern. More studies are needed to validate our hypothesis. [ABSTRACT FROM PUBLISHER]

Glaucoma and age-related macular degeneration (AMD) are the two leading causes of visual loss in the United States. We utilized a novel study design to perform a genome-wide association for both primary open angle glaucoma (POAG) and AMD. This study design utilized a two-stage process for hypothesis generation and validation, in which each disease cohort was utilized as a control for the other. A total of 400 POAG patients and 400 AMD patients were ascertained and genotyped at 500,000 loci. This study identified a novel association of complement component 7 (C7) to POAG. Additionally, an association of central corneal thickness, a known risk factor for POAG, was found to be associated with ribophorin II (RPN2). Linked monogenic loci for POAG and AMD were also evaluated for evidence of association, none of which were found to be significantly associated. However, several yielded putative associations requiring validation. Our data suggest that POAG is more genetically complex than AMD, with no common risk alleles of large effect. [ABSTRACT FROM AUTHOR]

This research proposes and empirically tests a customer switching intentions model from a disconfirmation perspective in a service failure and recovery context. Specifically, the research examines how initial (discrepancy between service failure expectation and service performance) and recovery (discrepancy between recovery expectation and recovery performance) disconfirmations influence satisfaction when a service failure occurs and a recovery offer is given, and subsequently impact switching intentions. The results support the hypotheses that both initial and recovery disconfirmations influence switching intentions via satisfaction. In addition, switching costs directly influence switching intentions and also moderate the effect of satisfaction on switching intentions. [ABSTRACT FROM AUTHOR]

Acute demyelinating optic neuritis is a common optic neuropathy in young adults. There is usually satisfactory visual recovery. However, some patients convert to multiple sclerosis (MS) with potential sequelae of neurological disability. The Optic Neuritis Treatment Trial in the United States was conducted prospectively for 15 years and provided valuable data about clinical course, efficacy of steroid treatment, and risk of conversion to MS. Compared to the many studies in Western countries, research concerning optic neuritis in Asia has so far not been extensive. However, cumulative evidence shows that various features of this disorder differ between patients of Caucasian and Oriental descent. In this article we review up-to-date studies on optic neuritis in Asia and compare the results with prior literature. Prospective and multi-centre studies are currently underway in these regions to increase our understanding of optic neuritis in Asia. [ABSTRACT FROM AUTHOR]

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRNA biomarkers that can be used to assess response to glucose lowering treatments would be useful. Using patient plasma samples from a subset of the Danish Metagenomics of the Human Intestinal Tract (MetaHIT) cohort, we characterized miRNAs from whole plasma, plasma-derived EVs, and EV-depleted plasma by small RNA-sequencing to identify T2DM associated miRNAs. We identified several miRNAs that exhibited concentration changes between controls and non-metformin treated T2DM patients and we validated a subset of these by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results showed that the concentrations of many T2DM-affected miRNAs in EV (but not in whole or EV-depleted plasma) decreased to levels close to those of healthy controls following metformin treatment. Among other potential uses of these differentially expressed miRNAs, some might be useful in assessing the response to metformin in T2DM patients. [ABSTRACT FROM AUTHOR]

Abstract: Changes in climate and emissions will affect future air quality. In this work, simulations of regional air quality during current (2001–2005) and future (2026–2030) winter and summer are conducted with the newly released CMAQ version 5.0 to examine the impacts of simulated future climate and anthropogenic emission projections on air quality over the U.S. Current meteorological and chemical predictions are evaluated against observations to assess the model's capability in reproducing the seasonal differences. WRF and CMAQ capture the overall observational spatial patterns and seasonal differences. Biases in model predictions are attributed to uncertainties in emissions, boundary conditions, and limitations in model physical and chemical treatments as well as the use of a coarse grid resolution. Increased temperatures (up to 3.18 °C) and decreased ventilation (up to 157 m in planetary boundary layer height) are found in both future winter and summer, with more prominent changes in winter. Increases in future temperatures result in increased isoprene and terpene emissions in winter and summer, driving the increase in maximum 8-h average O3 (up to 5.0 ppb) over the eastern U.S. in winter while decreases in NO x emissions drive the decrease in O3 over most of the U.S. in summer. Future PM2.5 concentrations in winter and summer and many of its components decrease due to decreases in primary anthropogenic emissions and the concentrations of secondary anthropogenic pollutants as well as increased precipitation in winter. Future winter and summer dry and wet deposition fluxes are spatially variable and increase with decreasing surface resistance and precipitation, respectively. They decrease with a decrease in ambient particulate concentrations. Anthropogenic emissions play a more important role in summer than in winter for future O3 and PM2.5 levels, with a dominance of the effects of significant emission reductions over those of climate change on future PM2.5 levels. [Copyright &y& Elsevier]

The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Genomic copy number variations (CNVs) have been strongly implicated in subjects with extreme obesity and coexisting developmental delay. To complement these previous studies, we addressed CNVs in common childhood obesity by examining children with a BMI in the upper 5th percentile but excluding any subject greater than three standard deviations from the mean in order to reduce severe cases in the cohort. We performed a whole-genome CNV survey of our cohort of 1080 defined European American (EA) childhood obesity cases and 2500 lean controls (< 50th percentile BMI) who were genotyped with 550,000 SNP markers. Positive findings were evaluated in an independent African American (AA) cohort of 1479 childhood obesity cases and 1575 lean controls. We identified 17 CNV loci that were unique to at least three EA cases and were both previously unreported in the public domain and validated via quantitative PCR. Eight of these loci (47.1%) also replicated exclusively in AA cases (six deletions and two duplications). Replicated deletion loci consisted of EDIL3, S1PR5, FOXP2, TBCA, ABCB5, and ZPLD1, whereas replicated duplication loci consisted of KIF2B and ARL15. We also observed evidence for a deletion at the EPHA6-UNQ6114 locus when the AA cohort was investigated as a discovery set. Although these variants may be individually rare, our results indicate that CNVs contribute to the genetic susceptibility of common childhood obesity in subjects of both European and African ancestry. [ABSTRACT FROM AUTHOR]

Health impacts of surface ozone (O 3) and fine particulate matter (PM 2.5) are of major concern worldwide. In this work, the Environmental Benefits Mapping and Analysis Program tool is applied to estimate the health and economic impacts of projected changes in O 3 and PM 2.5 in the U.S. in future (2046–2055) decade relative to current (2001–2010) decade under the Representative Concentration Pathway (RCP) 4.5 and 8.5 climate scenarios. Future annual-mean O 3 reductions under RCP 4.5 prevent ~1,800 all-cause mortality, 761 respiratory hospital admissions (HA), and ~1.2 million school loss days annually, and result in economic benefits of ~16 billion, 29 million, and 132 million U.S. dollars (USD), respectively. By contrast, the projected future annual-mean O 3 increases under RCP8.5 cause ~2,400 mortality, 941 respiratory HA, and ~1.6 million school loss days annually and result in economic disbenefits of ~21 billion, 36 million, and 175 million USD, respectively. Health benefits of reduced O 3 double under RCP4.5 and health dis-benefits of increased O 3 increase by 1.5 times under RCP8.5 in future with 2050 population and baseline incidence rate. Because of the reduction in projected future PM 2.5 over CONUS under both scenarios, the annual avoided all-cause deaths, cardiovascular HA, respiratory HA, and work loss days are ~63,000 and ~83,000, ~5,300 and ~7,000, ~12,000 and ~15,000, and ~7.8 million and ~10 million, respectively, leading to economic benefits of ~560 and ~740 billion, ~240 and ~320 million, ~450 and ~590 million, and ~1,400 and ~1,900 million USD for RCP4.5 and 8.5, respectively. Health benefits of reduced PM 2.5 for future almost double under both scenarios with the largest benefits in urban areas. RCP8.5 projects larger health and economic benefits due to a greater reduction in PM 2.5 but with a warmer atmosphere and higher O 3 pollution than RCP4.5. RCP4.5 leads to multiple-benefit goals including reduced O 3 and PM 2.5 , reduced mortality and morbidity, and saved costs. Greater reduction in future PM 2.5 under RCP4.5 should be considered to achieve larger multi-benefits. • Future O 3 reductions under RCP 4.5 prevent 1,797 mortality and save $16.1 billion/yr. • Future O 3 increases under RCP8.5 cause 2,379 mortality and cost $21.3 billion/yr. • Future PM 2.5 reductions for both scenarios avoid 63,087-82,917deaths, and save 564–741 billion/yr. • RCP8.5 gives larger health/cost benefits but a warmer climate and higher O 3 pollution than RCP4.5 • RCP4.5 gives multiple-benefits of reduced O 3 /PM 2.5 , reduced mortality/morbidity, & saved costs. [ABSTRACT FROM AUTHOR]

Abstract: Fugitive emissions of particulate matter (PM) raise public concerns due to their adverse impacts on human health and atmospheric visibility. Although the United States Environmental Protection Agency (USEPA) has not developed a standard method for quantifying the opacities of fugitive plumes, select states have developed human vision-based opacity methods for such applications. A digital photographic method, Digital Optical Method for fugitive plumes (DOMfugitive), is described herein for quantifying the opacities of fugitive plume emissions. Field campaigns were completed to evaluate this method by driving vehicles on unpaved roads to generate dust plumes. DOMfugitive was validated by performing simultaneous measurements using a co-located laser transmissometer. For 84% of the measurements, the individual absolute opacity difference values between the two methods were ≤15%. The average absolute opacity difference for all the measurements was 8.5%. The paired t-test showed no significant difference between the two methods at 99% confidence level. Comparisons of wavelength dependent opacities with grayscale opacities indicated that DOMfugitive was not sensitive to the wavelength in the visible spectrum evaluated during these field campaigns. These results encourage the development of a USEPA standard method for quantifying the opacities of fugitive PM plumes using digital photography, as an alternative to human-vision based approaches. [Copyright &y& Elsevier]

Background: Inadequate levels of vitamin D (VitD) have been linked to increased rates of various health conditions and mortality. However, little is known about the relationship between mortality outcomes and 25-hydroxyvitamin D [25(OH)D] levels in individuals with rheumatoid arthritis (RA). This study aimed to examine this association using data from the National Health and Nutrition Examination Survey., Methods: A cohort of 2,290 individuals aged 20 to 85 years with RA was analyzed. Lower 25(OH)D levels were inversely associated with all-cause mortality, with a hazard ratio (HR) of 0.91 (0.87 to 0.96) per 10 nmol/L increase. Comparatively, the HR for the VitD insufficiency group was 0.64 (0.50 to 0.83), and for the VitD sufficiency group, it was 0.60 (0.44 to 0.80), both compared to the VitD deficiency group. Cause-specific analysis showed that higher 25(OH)D levels were associated with reduced mortality from heart disease (HR: 0.88, 0.82 to 0.95) and malignant neoplasms (HR: 0.86, 0.79 to 0.94). No significant correlation was found between 25(OH)D levels and cause-specific mortalities for other conditions., Results: Stratified by gender, the HR for males was 0.92 (0.85 to 0.99) and for females was 0.91 (0.86 to 0.98) per 10 nmol/L increase in 25(OH)D levels. Among individuals aged 20-59 years, no significant correlation was observed, while for those aged 60 years and older, the HR was 0.86 (0.82 to 0.90) per 10 nmol/L increase. Nonlinear analysis identified a sharp increase in HR below 59.95 nmol/L, while HR remained below 1 for 25(OH)D levels above 59.95 nmol/L., Conclusion: This study reveals a strong negative correlation between 25(OH)D levels and overall mortality in individuals with RA. Notably, this association is particularly significant for mortality related to heart disease and malignant neoplasms. Targeted VitD supplementation should be emphasized, especially in individuals aged 60 years and older with RA. The proposed minimum threshold for adequate 25(OH)D levels in the RA population is 60 nmol/L., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Zhu, Yan, Wang, Chen, Zhang, Tian, Wang, Liu, Li, Meng and Wang.)

Background: Stroke represents a significant health crisis in the United States, claiming approximately 140,000 lives annually and ranking as the fifth leading cause of death., Objective: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2008, this study examines the correlation between various sleep characteristics and both stroke morbidity and all-cause mortality among U.S. adults., Methods: We applied logistic regression, Cox regression, and subgroup analyses to a sample of 7,827 adults aged 18 and older from NHANES 2005-2008. The study focused on six sleep characteristics: duration of sleep, sleep onset latency, snoring frequency, number of awakenings, frequency of leg spasms during sleep, and daytime sleepiness, analyzing their impacts on stroke incidence and mortality rates., Results: Participants had an average age of 45.80 ± 0.45 years, with females accounting for 48.13 % of the sample. Analysis revealed significant associations between sleep duration, onset latency, number of awakenings, leg spasms, and daytime sleepiness with stroke incidence. However, these associations weakened with increasing confounders. Additionally, stroke patients showed a higher likelihood of using sleep aids. The influence of sleep disturbances on stroke appeared more pronounced in females and younger demographics. An association was also noted between the number of awakenings, sleep duration, and stroke mortality rates CONCLUSIONS: The study reinforces the critical role of maintaining healthy sleep patterns in preventing strokes and enhancing stroke prognosis, emphasizing specific sleep disturbances as potential risk factors., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors., Methods: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties., Results: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: OR Black 0.83 (0.79-0.88), OR AIAN 0.66 (0.54-0.81); known stage: OR Black 0.87 (0.80-0.94), OR AIAN 0.63 (0.47-0.85); seeing an oncologist: OR Black 0.75 (0.71-0.79), OR AIAN 0.60 (0.47-0.72); locoregional treatment: OR Black 0.80 (0.76-0.84), OR AIAN 0.84 (0.68-1.02); systemic therapies: OR Black 0.90 (0.83-0.98), OR AIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits., Conclusions: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults., Methods: Participants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations., Results: The final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72-0.99), third (OR: 0.71, 95% CI: 0.58-0.85), and fourth (OR: 0.48, 95% CI: 0.38-0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51-0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk., Conclusion: This study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Deng, Nie, Tao, Li, Luo and Xia.)

Background and Objective: The association between magnesium depletion score (MDS) and the risk of chronic obstructive pulmonary disease (COPD) has not been examined to date. Meanwhile, the potential impact of dietary magnesium intake on this association remains unclear. This study aimed to investigate the influence of dietary magnesium intake on the association between MDS and COPD incidence., Methods: In this cross-sectional study using the National Health and Nutrition Examination Survey database, we analysed the relationship between MDS and COPD, while also exploring the role of dietary magnesium., Results: A total of 39 852 participants, including 1762 patients with COPD and 38 090 patients with non-COPD, were included in the analysis. After adjusting for confounding factors, our results demonstrated a significant association between higher MDS and increased COPD incidence (OR=1.48, 95% CI: 1.10 to 1.99). Furthermore, it was observed that dietary magnesium intake did not significantly impact this association., Conclusion: This study highlights a significant positive correlation between MDS and the incidence of COPD. Nonetheless, no significant alteration in this association was observed with dietary magnesium intake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the association of ultra-processed food consumption with all cause mortality and cause specific mortality., Design: Population based cohort study., Setting: Female registered nurses from 11 US states in the Nurses' Health Study (1984-2018) and male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018)., Participants: 74 563 women and 39 501 men with no history of cancer, cardiovascular diseases, or diabetes at baseline., Main Outcome Measures: Multivariable Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for the association of ultra-processed food intake measured by semiquantitative food frequency questionnaire every four years with all cause mortality and cause specific mortality due to cancer, cardiovascular, and other causes (including respiratory and neurodegenerative causes)., Results: 30 188 deaths of women and 18 005 deaths of men were documented during a median of 34 and 31 years of follow-up, respectively. Compared with those in the lowest quarter of ultra-processed food consumption, participants in the highest quarter had a 4% higher all cause mortality (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07) and 9% higher mortality from causes other than cancer or cardiovascular diseases (1.09, 1.05 to 1.13). The all cause mortality rate among participants in the lowest and highest quarter was 1472 and 1536 per 100 000 person years, respectively. No associations were found for cancer or cardiovascular mortality. Meat/poultry/seafood based ready-to-eat products (for example, processed meat) consistently showed strong associations with mortality outcomes (hazard ratios ranged from 1.06 to 1.43). Sugar sweetened and artificially sweetened beverages (1.09, 1.07 to 1.12), dairy based desserts (1.07, 1.04 to 1.10), and ultra-processed breakfast food (1.04, 1.02 to 1.07) were also associated with higher all cause mortality. No consistent associations between ultra-processed foods and mortality were observed within each quarter of dietary quality assessed by the Alternative Healthy Eating Index-2010 score, whereas better dietary quality showed an inverse association with mortality within each quarter of ultra-processed foods., Conclusions: This study found that a higher intake of ultra-processed foods was associated with slightly higher all cause mortality, driven by causes other than cancer and cardiovascular diseases. The associations varied across subgroups of ultra-processed foods, with meat/poultry/seafood based ready-to-eat products showing particularly strong associations with mortality., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; NK received a consulting fee from the Pan American Health Organization for three months on the topic of nutrition disclosure initiatives and nutrient profiling models; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

(1) Background: Radiation-induced thrombocytopenia (RIT) often occurs in cancer patients undergoing radiation therapy, which can result in morbidity and even death. However, a notable deficiency exists in the availability of specific drugs designed for the treatment of RIT. (2) Methods: In our pursuit of new drugs for RIT treatment, we employed three deep learning (DL) algorithms: convolutional neural network (CNN), deep neural network (DNN), and a hybrid neural network that combines the computational characteristics of the two. These algorithms construct computational models that can screen compounds for drug activity by utilizing the distinct physicochemical properties of the molecules. The best model underwent testing using a set of 10 drugs endorsed by the US Food and Drug Administration (FDA) specifically for the treatment of thrombocytopenia. (3) Results: The Hybrid CNN+DNN (HCD) model demonstrated the most effective predictive performance on the test dataset, achieving an accuracy of 98.3% and a precision of 97.0%. Both metrics surpassed the performance of the other models, and the model predicted that seven FDA drugs would exhibit activity. Isochlorogenic acid A, identified through screening the Chinese Pharmacopoeia Natural Product Library, was subsequently subjected to experimental verification. The results indicated a substantial enhancement in the differentiation and maturation of megakaryocytes (MKs), along with a notable increase in platelet production. (4) Conclusions: This underscores the potential therapeutic efficacy of isochlorogenic acid A in addressing RIT.

Objective: To investigate the relationship between dietary carotenoid intake and sleep duration., Methods: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration., Results: Multinominal logistic regression presented that people with higher intakes of α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where β-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while β-carotene, α-carotene, and β-cryptoxanthin were the main factors related to the lower risk of long sleep duration., Conclusion: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers., (© 2023. The Author(s).)

Background: Racial and ethnic disparities in guideline-recommended breast cancer treatment are well documented, however studies including diagnostic and staging procedures necessary to determine treatment indications are lacking. The purpose of this study was to characterize patterns in delivery of evidence-based services for the diagnosis, clinical workup, and first-line treatment of breast cancer by race-ethnicity., Methods: SEER-Medicare data were used to identify women diagnosed with invasive breast cancer between 2000 and 2017 at age 66 or older (n = 2,15,605). Evidence-based services included diagnostic procedures (diagnostic mammography and breast biopsy), clinical workup (stage and grade determination, lymph node biopsy, and HR and HER2 status determination), and treatment initiation (surgery, radiation, chemotherapy, hormone therapy, and HER2-targeted therapy). Poisson regression was used to estimate rate ratios (RR) and 95% confidence intervals (CI) for each service., Results: Black and American Indian/Alaska Native (AIAN) women had significantly lower rates of evidence-based care across the continuum from diagnostics through first-line treatment compared to non-Hispanic White (NHW) women. AIAN women had the lowest rates of HER2-targeted therapy and hormone therapy initiation. While Black women also had lower initiation of HER2-targeted therapy than NHW, differences in hormone therapy were not observed., Conclusions: Our findings suggest patterns along the continuum of care from diagnostic procedures to treatment initiation may differ across race-ethnicity groups., Impact: Efforts to improve delivery of guideline-concordant treatment and mitigate racial-ethnic disparities in healthcare and survival should include procedures performed as part of the diagnosis, clinical workup, and staging processes., (©2023 American Association for Cancer Research.)

Background: Attention deficit/hyperactivity disorder (ADHD) has been identified as a risk factor for obesity in both children and adolescents. However, the mechanisms underlying the relationship between ADHD and obesity are still unclear. This study aimed to test a theoretical model of whether anxiety/depression is an intermediary factor in the ADHD-obesity relationship., Methods: Data were derived from the National Health Interview Survey (NHIS), a principal source of information on the health of the civilian noninstitutionalized population of the United States. A total of 35,108 adolescents aged 12-17 years old from 2010-2015 NHIS and 2016-2018 NHIS representing 46,550,729 individuals in the weighted population, had a parent-reported previous ADHD diagnosis, emotional problems, and height and weight data. Mediation analyses were used to explore whether anxiety/depression is an intermediary factor in the relationship between ever having ADHD and obesity. Mediation analyses were performed using multiple logistic regressions., Results: The findings showed that ADHD was a predictor of obesity. This relationship was partially mediated by depression(2010-2015: β=0.28, 95%CI:0.13-0.43; 2016-2018: β=0.26, 95%CI:0.03-0.49), as well as anxiety (2010-2015: β=0.28, 95%CI:0.18-0.38)., Conclusions: Our study suggests the hypothetical role of depression and anxiety as underlying mechanisms in the association between ever having ADHD and obesity in adolescents. When treating children with ADHD, clinicians need to be particularly attentive to whether they show emotional problems and use interventions to eliminate anxiety/depression to protect against obesity., (© 2023. The Author(s).)

To assess the clinical implementation of the 2017 Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists, identify content that may result in classification inconsistencies, and evaluate implementation barriers, an Association for Molecular Pathology Working Group conducted variant interpretation challenges and a guideline implementation survey. A total of 134 participants participated in the variant interpretation challenges, consisting of 11 variants in four cancer cases. Results demonstrate 86% (range, 54% to 94%) of the respondents correctly classified clinically significant variants, variants of uncertain significance, and benign/likely benign variants; however, only 59% (range, 39% to 84%) of responses agreed with the working group's consensus intended responses regarding both tiers and categories of clinical significance. In the implementation survey, 71% (157/220) of respondents have implemented the 2017 guidelines for variant classification and reporting either with or without modifications. Collectively, this study demonstrates that, although they may not yet be optimized, the 2017 guideline recommendations are being adopted for standardized somatic variant classification. The working group identified significant areas for future guideline improvement, including the need for a more granular and comprehensive classification system and education resources to meet the growing needs of both laboratory professionals and medical oncologists., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes is a critical contributor to the pathogenesis of cardiovascular diseases. Klotho is an anti-aging protein with cardiovascular-renal protective effects. However, the relationship between serum Klotho levels and diabetes remains poorly understood., Objectives: This study aimed to investigate the relationship between serum Klotho levels and diabetes in US adults., Methods: We analyzed the cross-sectional data obtained from 13751 subjects aged 40-79 years in the National Health and Nutrition Examination Survey (NHANES) (2007-2016). Serum Klotho concentration was measured using an enzyme-linked immunosorbent assay (ELISA) and categorized into four quartiles (Q1-Q4). Multivariate logistic regression and restricted cubic spline (RCS) regression were conducted to explore the association between serum Klotho levels and the prevalence of diabetes., Results: As compared with quartile 1, serum Klotho levels in quartiles 2-4 yielded odds ratios (OR) (95% CI) of diabetes of 0.96 (0.80-1.15), 0.98 (0.82-1.18), and 1.25 (1.04-1.50), respectively, after covariate adjustment ( P for trend = 0.018). The results implied an increased risk of diabetes. The RCS plot showed a U-shaped relationship linking serum Klotho levels with diabetes ( P for nonlinearity = 0.003)., Conclusions: In summary, a nonlinear and positive association was found between serum Klotho levels and the prevalence of diabetes. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Mao, Lu, Liu, Sun, Li, Li, Ding, Zhang, Hong and Xu.)

Interest in incorporating art into radiology has been growing in recent years. Radiological societies have begun to acknowledge the benefits art can bring to our field. Given this growing interest, a task force was created in 2021 to carry out integration of the arts into the annual American College of Radiology (ACR) meeting. Experiences of this task force are described, including consideration of benefits of integrating art in radiology practice and education as well as strategies, outcomes, and future directions for melding arts with radiology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Election forecasting has been traditionally dominated by subjective surveys and polls or methods centered upon them. We have developed a novel platform for forecasting elections based on agent-based modeling (ABM), which is entirely independent from surveys and polls. The platform uses statistical results from objective data along with simulation models to capture how voters have voted in past elections and how they are likely to vote in an upcoming election. We screen for models that can reproduce results that are very close to the actual results of historical elections and then deploy these selected models to forecast an upcoming election with simulations by combining extrapolated data from historical demographic record and more updated data on economic growth, employment, shock events, and other factors. Here, we report the results of two recent experiments of real-time election forecasting: the 2020 general election in Taiwan and six states in the 2020 general election in the United States. Our mostly objective method using ABM may transform how elections are forecasted and studied., Competing Interests: The authors have declared that no competing interests exist.

Background: Endoscopic screening and adherence to a healthy lifestyle are major avenues for colorectal cancer (CRC) prevention. We investigated changes in lifestyles after endoscopic screening., Methods: We drew data from 76,303 pairs of time- and age-matched individuals who had and had not, respectively, reported first time endoscopic screening, in the 3 cohorts (Nurses' Health Study I and II and the Health Professionals Follow-up Study). Detailed information was collected every 2-4 years on endoscopy screening, 12 lifestyle factors (including smoking, physical activity, regular use of aspirin/nonsteroidal anti-inflammatory drugs, body weight, and 8 dietary factors), and adherence to a healthy lifestyle based on a score defined by 5 major lifestyle factors (smoking, alcohol, body weight, physical activity, and diet). We assessed changes in lifestyle from pre- to post-screening periods for the matched pairs. We also conducted subgroup analysis according to screening findings (negative, low- and high-risk polyps, and CRC)., Results: Endoscopic screening was associated with higher prevalence of adherence to a healthy lifestyle (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.16). The association strengthened with the severity of the screening findings, with an OR of 1.09 (95% CI, 1.03-1.15) for negative screening, 1.19 (95% CI, 1.07-1.33) for low-risk polyps, 1.42 (95% CI, 1.14-1.77) for high-risk polyps, and 1.55 (95% CI, 1.17-2.05) for CRC. The individual lifestyle factors and diet showed modest change., Conclusions: Endoscopic screening was associated with a modest improvement in healthy lifestyles, particularly in individuals with more severe endoscopic findings. Further efforts of integrating lifestyle medicine into the screening setting are needed, to better leverage the teachable moment in improving CRC prevention., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Micromobility sharing platforms have involved skyrocketing numbers of users in multiple countries since 2010. However, few studies have examined the overall impact of the growing micromobility market on road injuries., Method: We use road injury data from the Global Burden of Disease Study database to examine the effect of age, period, and cohort on micromobility injury-related deaths and incidence. We compared four countries that vary in demographic background and road infrastructure. By comparing the countries, we analyzed the relationship between the trends in road injuries and these factors., Results: We found an overall upward trend in micromobility injuries. A higher risk of micromobility-related injuries was witnessed in China and the US in 2015-2019, and people older than 45 showed a growing micromobility-related mortality and incidence rate in China, India, and the US. Cohorts after 1960 showed higher micromobility injury incidence risks in China and India, but the population born after 1990 in India showed a slightly lower risk compared to those before it., Conclusions: The boosted usage of micromobility devices explains these increasing trends. Road infrastructure and separated traffic ease the collisions from micromobility devices. The overall situation calls for improvement in legislation as well as road infrastructure., (© 2022. The Author(s).)

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access., (© 2022. The Author(s).)

Most risk prediction models for colorectal cancer (CRC) are based on questionnaires and show a modest discriminatory ability. Therefore, we aim to develop risk prediction models incorporating plasma biomarkers for CRC to improve discrimination. We assessed the predictivity of 11 biomarkers in 736 men in the Health Professionals Follow-up Study and 639 women in the Nurses' Health Study. We used stepwise logistic regression to examine whether a set of biomarkers improved the predictivity on the basis of predictors in the National Cancer Institute's (NCI) Colorectal Cancer Risk Assessment Tool. Model discrimination was assessed using C-statistics. Bootstrap with 500 randomly sampled replicates was used for internal validation. The models containing each biomarker generated a C-statistic ranging from 0.50 to 0.59 in men and 0.50 to 0.54 in women. The NCI model demonstrated a C-statistic (95% CI) of 0.67 (0.62-0.71) in men and 0.58 (0.54-0.63) in women. Through stepwise selection of biomarkers, the C-statistic increased to 0.70 (0.66-0.74) in men after adding growth/differentiation factor 15, total adiponectin, sex hormone binding globulin and tumor necrosis factor receptor superfamily member 1B (P for difference = 0.008); and increased to 0.62 (0.57-0.66) in women after further including insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 (P for difference = .06). The NCI + selected biomarkers model was internally validated with a C-statistic (95% CI) of 0.73 (0.70-0.77) in men and 0.66 (0.61-0.70) in women. Circulating plasma biomarkers may improve the performance of risk factor-based prediction model for CRC., (© 2021 UICC.)

Globally, the total estimated number of people living with depression increased by 18.4% between 2005 and 2015, with the prevalence being 4.8% in 2015. Many nutrient and diet patterns are proven to be correlated to depression, so we conducted this analysis to explore whether the Healthy Eating Index 2015 (HEI-2015) score is associated with depression, and possibly to provide dietary measures to reduce the risk of depression. Data came from the National Health and Nutrition Examination Survey (2005-2016), a cross-sectional and nationally representative database. The analytic sample was limited to adults: (1) age ≥20 with complete information of HEI-2015 and depression; (2) no missing data of demographics, BMI, drinking, smoking, and fasting plasma glucose. HEI-2015 was calculated using the Dietary Interview: Total Nutrient Intakes, First Day data file. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Weighted logistic regression models were used to explore the relationship between the HEI-2015 score and depression. The final study sample included 10,349 adults, with 51.4% of them being men, representing a population of about 167.8 million non-institutionalized U.S. adults. After multivariable adjustment, average HEI status (OR: 0.848, 95% CI: 0.846-0.849) and optimal HEI status (OR: 0.455, 95% CI: 0.453-0.456) were associated with reduced odds of depression. Poor diet quality is significantly associated with elevated depressive symptoms in U.S. adults. Aligning with the Dietary Guidelines for Americans reduces the risk of depression.

Selecting an appropriate exposure measure and functional form for Safety Performance Functions (SPFs) is critical in precisely predicting crash counts by different crash types for intersections. This study proposes a new approach, namely Generalized Negative Binomial-P (GNB-P) model, to model the complex relationship between crashes and different exposure measures by crash type for intersections, which helps not only identify the most reliable exposure measure for intersection SPFs, but also explore the most appropriate functional form of the NB models. To this end, three types of SPF functional forms, namely Power function, Hoerl function 1 and Hoerl function 2 with different exposure measures including major road AADT, minor road AADT and total AADT were estimated by crash type for stop-controlled and two types of signalized intersections. The over-dispersion of the SPF models was estimated using the exposure measures to account for crash data variation across different intersections. The SPF estimation results highlighted that the mean-variance structure of NB models is not consistent and varies by crash data. The over-dispersion of SPFs by crash type is not constant and varies across different intersections. The minor road AADT is shown to be positively correlated with the over-dispersion of SPFs in estimating crash counts for Same-Direction Crashes (SDC), Intersecting-Direction Crashes (IDC) and Single-Vehicle Crashes (SVC). Estimating the over-dispersion using exposure measures results in more reliable SPF results. Furthermore, it is found that the Power function with major road and minor road AADT as the exposure measure performs the best in estimating SPFs for Opposite-Direction Crashes (ODC). The Hoerl function 2 with total AADT and the proportion of minor road AADT over the total as the exposure measure performs the best in estimating SVC SPFs for intersections. The Hoerl function 1 with major road and minor road AADT as the exposure measure is more accurate in estimating SPFs for both SDC and IDC., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (KCNQ4, TECTA, WFS1) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in KCNQ4; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for TECTA and WFS1. Identifying the drivers of ethnic differences will refine our understanding of phenotype-genotype relationships and the biology of hearing and deafness.

Background It remains unknown whether individuals who regularly use preventive medications receive the same benefit from healthy lifestyle as those who do not use medications. We aimed to examine the associations of healthy lifestyle with mortality according to use of major preventive medications, including aspirin, antihypertensives, and lipid-lowering medications. Methods and Results Among 79 043 women in the Nurses' Health Study (1988-2014) and 39 544 men in the Health Professionals Follow-up Study (1986-2014), we defined a healthy lifestyle score based on body mass index, smoking, physical activity, diet, and alcohol intake. We estimated multivariable hazard ratios (HRs) and population-attributable risks of death from any cause, cardiovascular disease, cancer, and other causes in relation to healthy lifestyle according to medication use. We documented 35 195 deaths. A similar association of healthy lifestyle score with lower all-cause mortality was observed among medication users (HR, 0.82 per unit increment; 95% CI, 0.81-0.82) and nonusers (HR, 0.81; 95% CI, 0.79-0.83) ( P interaction=0.54). The fraction of premature deaths that might be prevented by adherence to the 5 healthy lifestyle factors among medication users and nonusers was 38% (95% CI, 32%-42%) and 40% (95% CI, 29%-50%) for all-cause mortality, 37% (95% CI, 27%-46%) and 45% (95% CI, 18%-66%) for cardiovascular disease mortality, and 38% (95% CI, 28%-46%) and 33% (95% CI, 14%-49%) for cancer mortality, respectively. Conclusions Adherence to a healthy lifestyle confers substantial benefit for prevention of premature death among both regular users and nonusers of preventive medications. Adherence to a healthy lifestyle remains important even among individuals regularly using preventive medications.

To investigate the correlation between echinodermmicro tubule associated protein-like 4 (EML4)-anaplasticlymphomakinase (ALK), epidermal growth factor receptor (EGFR) and clinicopathological features in patients diagnosed with lung adenocarcinoma according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) international multidisciplinary classification of lung adenocarcinoma.Ninety patients diagnosed with lung adenocarcinoma underwent surgical pathological classification. Ventana immunohistochemical staining of the EML4-ALK was performed. The mutation of EGFR and EML4-ALK was detected by real-time polymerase chain reaction (RT-PCR) using the amplification refractory mutation system.The positive rate of EML4-ALK mutation was calculated as 6.7% (6/90), dominantly occurring in patients aged < 60 years. However, it was not correlated with the gender, smoking history, maximal tumor diameter, pleural invasion, lymphatic metastasis, or clinical staging. EML4-ALK fusion gene mutation was mainly associated with the predominant subtypes of acinar and solid tumors with mucin secretion. The mutation rate of EGFR was 60% (27/45). EGFR gene mutation mainly occurred in the female, those with no smoking history and tumor size < 3 cm, whereas it had no association with age, pleural invasion, lymphatic metastasis, or clinical staging. It was histologically characterized with micropapillary, lepidic, and papillary subtypes.The mutation rate of EML4-ALK is relatively high in lung adenocarcinoma patients aged<60 years, pathologically characterized with acinar and solid subtypes with mucin secretion. Female patients with no smoking habit, tumor size<3 cm, pathologically characterized with micropapillary, lepidic, and papillary subtypes had a high mutation rate of EGFR.

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction., (© 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Objective: To investigate clear cell papillary (CCP) renal cell carcinoma (RCC), an uncommon tumor of low malignant potential characterized by low-grade, clear cells, showing papillary and tubular architecture. This relatively newly described entity is still being characterized. We present our series of CCP RCC with new clinical and imaging findings., Materials and Methods: We reviewed the clinical, pathologic, and imaging findings of 28 CCP RCCs in 21 patients identified from our institution between 2010 and 2016., Results: Sixteen of 21 (76%) patients were African American with an equal male-to-female ratio. Mean follow-up was 26.1 ± 16.9 months. Mean age at diagnosis was 58.3 ± 10.7 years, and mean preoperative creatinine was 2.7 ± 2.9 mg/dL. End-stage renal disease or chronic kidney disease was present in 10 of 21 (47.6%) patients. Mean tumor size was 2.2 ± 1.5 cm. All cases were stage pT1, and 25 of 28 (89%) tumors were grade 2. No necrosis or sarcomatoid features were identified. Two patients had synchronous clear cell RCC and 1 patient had synchronous papillary RCC. No recurrence or metastases were identified. On imaging, the majority of the lesions were solid, with relatively low-level enhancement, similar to papillary RCC, with regions of heterogeneous hyper-enhancement, similar to clear cell RCC. The rate of growth on serial imaging was comparable with that observed for other low-staged RCCs., Conclusion: In our series, CCP RCC was seen more commonly in African American patients and associated with end-stage renal disease or chronic kidney disease. Imaging characteristics are similar in both clear cell RCC and papillary RCC. A nephron-sparing approach is recommended when surgically feasible., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Gastric cancer (GC) is a major global cancer burden and the second most common cause of global cancer-related deaths. The addition of anti-ERBB2 (HER2) targeted therapy to chemotherapy improves survival for ERBB2-amplified advanced GC patients; however, the majority of GC patients do not harbor this alteration and thus cannot benefit from targeted therapy under current practice paradigms., Materials and Methods: Prospective comprehensive genomic profiling of 116 predominantly locally advanced or metastatic (90.0%) gastric cancer cases was performed to identify genomic alterations (GAs) associated with a potential response to targeted therapies approved by the U.S. Food and Drug Administration or targeted therapy-based clinical trials., Results: Overall, 78% of GC cases harbored one clinically relevant GA or more, with the most frequent alterations being found in TP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), and MET (6.0%). Receptor tyrosine kinase genomic alterations were detected in 20.6% of cases, primarily ERBB2, FGFR2, and MET amplification, with ERBB2 alterations evenly split between amplifications and base substitutions. Rare BRAF mutations (2.6%) were also observed. One MET-amplified GC patient responded for 5 months to crizotinib, a multitargeted ALK/ROS1/MET inhibitor., Conclusion: Comprehensive genomic profiling of GC identifies clinically relevant GAs that suggest benefit from targeted therapy including MET-amplified GC and ERBB2 base substitutions., (©AlphaMed Press.)

Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

East Chicago, Indiana is a heavily industrialized community bisected by the Indiana Harbor and Ship Canal, which volatilizes ~7.5 kg/yr polychlorinated biphenyls (PCBs). In contrast, the rural Columbus Junction, Iowa area has no known current or past PCB industrial sources. Blood from children and their mothers from these communities were collected April 2008 to January 2009 (n = 177). Sera were analyzed for all 209 PCBs and 4 hydroxylated PCBs (OH-PCBs). Sum PCBs ranged from nondetect to 658 ng/g lw (median = 33.5 ng/g lw). Sum OH-PCBs ranged from nondetect to 1.2 ng/g fw (median = 0.07 ng/g fw). These concentrations are similar to those reported in other populations without high dietary PCB intake. Differences between the two communities were subtle. PCBs were detected in more East Chicago mothers and children than Columbus Junction mothers and children, and children from East Chicago were enriched in lower-molecular weight PCBs. East Chicago and Columbus Junction residents had similar levels of total and individual PCBs and OH-PCBs in their blood. Concentrations of parent PCBs correlated with concentrations of OH-PCBs. This is the first temporally and methodologically consistent study to evaluate all 209 PCBs and major metabolites in two generations of people living in urban and rural areas of the United States.

Recent genome wide association studies (GWAS) have revealed a number of genetic variants robustly associated with bone mineral density (BMD) and/or osteoporosis. Evidence from epidemiological and clinical studies has shown an association between BMD and BMI, presumably as a consequence of bone loading. We investigated the 23 previously published BMD GWAS-derived loci in the context of childhood obesity by leveraging our existing genome-wide genotyped European American cohort of 1106 obese children (BMI ≥ 95th percentile) and 5997 controls (BMI < 95th percentile). Evidence of association was only observed at one locus, namely Osterix (SP7), with the G allele of rs2016266 being significantly over-represented among childhood obesity cases (P = 2.85 × 10(-3)). When restricting these analyses to each gender, we observed strong association between rs2016266 and childhood obesity in females (477 cases and 2867 controls; P = 3.56 × 10(-4)), which survived adjustment for all tests applied. However, no evidence of association was observed among males. Interestingly, Osterix is the only GWAS locus uncovered to date that has also been previously implicated in the determination of BMD in childhood. In conclusion, these findings indicate that a well established variant at the Osterix locus associated with increased BMD is also associated with childhood obesity primarily in females.

Purpose: To determine the role of the recently discovered primary open angle glaucoma (POAG) risk factor mapped to chromosome 7q31 in glaucoma patients from Iowa and to determine the expression pattern of genes in the locus in human eyes., Methods: A cohort of 545 POAG patients and 297 control subjects from Iowa were genotyped with a single nucleotide polymorphism (SNP; rs4236601) in the chromosome 7q31 locus using a quantitative polymerase chain reaction (PCR) assay. The expression of genes within the 7q31 locus, caveolin-1 (CAV1) and caveolin-2 (CAV2) in human eyes was investigated with immunohistochemistry., Results: The minor allele frequency (MAF) of rs4236601 was 27% in control subjects and 29% in POAG patients. We detected no statistical difference when we compared the allele frequencies of rs4236601 between POAG patients and control subjects (p=0.5). Similarly, we detected no statistical difference in the frequency of the three possible rs4236601 genotypes between patients and controls (p=0.22). Immunohistochemistry showed caveolin expression in human retina, ciliary muscle, trabecular meshwork, and Schlemm's canal. In our small cohort of donor eyes, the genotype of rs4236601 did not obviously influence labeling intensity or distribution of CAV1 and CAV2 in the retina., Conclusions: A genome-wide association study of subjects from Iceland mapped the first common genetic risk factor for POAG to a small region of the genome on chromosome 7q31 that contains the caveolin genes CAV1 and CAV2. We were unable to detect this association in our patients from Iowa, suggesting that this risk factor may not have a strong effect in all populations.