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Background: Limited studies have explored the joint effect of physical activity (PA) and dietary quality (DQ) on the mortality outcomes of the cancer population. The authors aim to investigate the separate and joint prognostic effect of PA and DQ on the survival of US cancer survivors., Methods: Data of cancer survivors ( n =3007, representing 22 million cancer survivors) were from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PA was assessed using the self-reported Global Physical Activity Questionnaire (GPAQ) and DQ was evaluated through the Health Eating Index-2015 (HEI-2015). Kaplan-Meier (KM) curves and the Cox proportional hazard model were used to evaluate the associations between separate and joint prognostic effects of PA and DQ with mortality outcomes among cancer survivors., Results: In the joint analyses, cancer survivors with sufficiently active PA (≥600 MET-min/week) and qualified DQ (≥60) presented reduced risks of all-cause mortality (HR 0.45, 95% CI: 0.35-0.59) as compared with each lifestyle intervention separately. Meanwhile, the joint effects of either insufficiently or sufficiently active PA (>0 MET-min/week) and qualified DQ (≥60) were associated with lower risks for cancer (HR 0.60, 95% CI: 0.40-0.90) and noncancer mortality (HR 0.43, 95% CI: 0.32-0.59)., Conclusions: Our study highlights the combination of active PA and qualified DQ was strongly associated with reduced mortality risk of cancer survivors. Our findings might help to refine the lifestyle intervention recommendations for this population., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM 2·5 concentrations and their attributable mortality burden across the USA., Methods: In this study, we derived daily concentrations of PM 2·5 and its highly toxic black carbon component at a 1-km resolution in the USA from 2000 to 2020 via deep learning that integrated big data from satellites, models, and surface observations. We estimated the annual PM 2·5 -attributable and black carbon-attributable mortality burden at each 1-km 2 grid using concentration-response functions collected from a national cohort study and a meta-analysis study, respectively. We investigated the spatiotemporal linear-regressed trends in PM 2·5 and black carbon pollution and their associated premature deaths from 2000 to 2020, and the impact of wildfires on air quality and public health., Findings: Our results showed that PM 2·5 and black carbon estimates are reliable, with sample-based cross-validated coefficients of determination of 0·82 and 0·80, respectively, for daily estimates (0·97 and 0·95 for monthly estimates). Both PM 2·5 and black carbon in the USA showed significantly decreasing trends overall during 2000 to 2020 (22% decrease for PM 2·5 and 11% decrease for black carbon), leading to a reduction of around 4200 premature deaths per year (95% CI 2960-5050). However, since 2010, the decreasing trends of fine particles and premature deaths have reversed to increase in the western USA (55% increase in PM 2·5 , 86% increase in black carbon, and increase of 670 premature deaths [460-810]), while remaining mostly unchanged in the eastern USA. The western USA showed large interannual fluctuations that were attributable to the increasing incidence of wildfires. Furthermore, the black carbon-to-PM 2·5 mass ratio increased annually by 2·4% across the USA, mainly due to increasing wildfire emissions in the western USA and more rapid reductions of other components in the eastern USA, suggesting a potential increase in the relative toxicity of PM 2·5 . 100% of populated areas in the USA have experienced at least one day of PM 2·5 pollution exceeding the daily air quality guideline level of 15 μg/m 3 during 2000-2020, with 99% experiencing at least 7 days and 85% experiencing at least 30 days. The recent widespread wildfires have greatly increased the daily exposure risks in the western USA, and have also impacted the midwestern USA due to the long-range transport of smoke., Interpretation: Wildfires have become increasingly intensive and frequent in the western USA, resulting in a significant increase in smoke-related emissions in populated areas. This increase is likely to have contributed to a decline in air quality and an increase in attributable mortality. Reducing fire risk via effective policies besides mitigation of climate warming, such as wildfire prevention and management, forest restoration, and new revenue generation, could substantially improve air quality and public health in the coming decades., Funding: National Aeronautics and Space Administration (NASA) Applied Science programme, NASA MODIS maintenance programme, NASA MAIA satellite mission programme, NASA GMAO core fund, National Oceanic and Atmospheric Administration (NOAA) GEO-XO project, NOAA Atmospheric Chemistry, Carbon Cycle, and Climate (AC4) programme, and NOAA Educational Partnership Program with Minority Serving Institutions., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Artificial Light at Night (ALAN) is an emerging health risk factor that has been linked to a wide range of adverse health effects. Recent study suggested that disadvantaged neighborhoods may be exposed to higher levels of ALAN. Understanding how social disadvantage correlates with ALAN levels is essential for identifying the vulnerable populations and for informing lighting policy., Methods: We used satellite data from the National Aeronautics and Space Administration's (NASA) Black Marble data product to quantify annual ALAN levels (2012-2019), and the Center for Disease Control and Prevention's (CDC) Social Vulnerability Index (SVI) to quantify social disadvantage, both at the US census tract level. We examined the relationship between the ALAN and SVI (overall and domain-specific) in over 70,000 tracts in the Contiguous U.S., and investigated the heterogeneities in this relationship by the rural-urban status and US regions (i.e., Northeast, Midwest, South, West)., Results: We found a significant positive relationship between SVI and ALAN levels. On average, the ALAN level in the top 20% most vulnerable communities was 2.46-fold higher than that in the 20% least vulnerable communities (beta coefficient (95% confidence interval) for log-transformed ALAN, 0.90 (0.88, 0.92)). Of the four SVI domains, minority and language status emerged as strong predictors of ALAN levels. Our stratified analysis showed considerable and complex heterogeneities across different rural-urban categories, with the association between greater vulnerability and higher ALAN primarily observed in urban cores and rural areas. We also found regional differences in the association between ALAN and both overall SVI and SVI domains., Conclusions: Our study suggested ALAN as an environmental justice issue that may carry important public health implications. Funding National Aeronautics and Space Administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In 2014, 2016, and 2018, the United States experienced unprecedented spikes in pediatric cases of acute flaccid myelitis (AFM), which is a poliomyelitis-like paralytic illness. Accumulating clinical, immunological, and epidemiological evidence has identified enterovirus D68 (EV-D68) as a major causative agent of these biennial AFM outbreaks. There are currently no available FDA-approved antivirals that are effective against EV-D68, and the treatment for EV-D68-associated AFM is primarily supportive. Telaprevir is an food and drug administration (FDA)-approved protease inhibitor that irreversibly binds the EV-D68 2A protease and inhibits EV-D68 replication in vitro . Here, we utilize a murine model of EV-D68 associated AFM to show that early telaprevir treatment improves paralysis outcomes in Swiss Webster (SW) mice. Telaprevir reduces both viral titer and apoptotic activity in both muscles and spinal cords at early disease time points, which results in improved AFM outcomes in infected mice. Following intramuscular inoculation in mice, EV-D68 infection results in a stereotypic pattern of weakness that is reflected by the loss of the innervating motor neuron population, in sequential order, of the ipsilateral (injected) hindlimb, the contralateral hindlimb, and then the forelimbs. Telaprevir treatment preserved motor neuron populations and reduced weakness in limbs beyond the injected hindlimb. The effects of telaprevir were not seen when the treatment was delayed, and toxicity limited doses beyond 35 mg/kg. These studies are a proof of principle, provide the first evidence of benefit of an FDA-approved antiviral drug with which to treat AFM, and emphasize both the need to develop better tolerated therapies that remain efficacious when administered after viral infections and the development of clinical symptoms. IMPORTANCE Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have resulted in over 600 cases of a paralytic illness that is known as AFM. AFM is a predominantly pediatric disease with no FDA-approved treatment, and many patients show minimal recovery from limb weakness. Telaprevir is an FDA-approved antiviral that has been shown to inhibit EV-D68 in vitro . Here, we demonstrate that a telaprevir treatment that is given concurrently with an EV-D68 infection improves AFM outcomes in mice by reducing apoptosis and viral titers at early time points. Telaprevir also protected motor neurons and improved paralysis outcomes in limbs beyond the site of viral inoculation. This study improves understanding of EV-D68 pathogenesis in the mouse model of AFM. This study serves as a proof of principle for the first FDA-approved drug that has been shown to improve AFM outcomes and have in vivo efficacy against EV-D68 as well as underlines the importance of the continued development of EV-D68 antivirals., Competing Interests: The authors declare no conflict of interest.

Blood always shows some immune changes after spinal cord injury (SCI), and detection of such changes in blood may be helpful for diagnosis and treatment of SCI. However, studies to date on blood immune changes after SCI in humans are not comprehensive. Therefore, to obtain the characteristics of blood immune changes and immunodiagnostic blood biomarkers of SCI and its different grades, a human blood transcriptome sequencing dataset was downloaded and analyzed to obtain differentially expressed immune-related genes (DEIGs), related functions and signaling pathways related to SCI and its various grades. Characteristic biomarkers of SCI and its different grades were identified by using weighted gene coexpression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) logistic regression. Expression of biomarkers was verified through experiments. The area under the curve (AUC) of biomarkers was calculated to evaluate their diagnostic value, and differences in immune cell content were examined. In this study, 17 kinds of immune cells with different contents between the SCI group and healthy control (HC) group were identified, with 7 immune cell types being significantly increased. Differences in the content of immune cells between different grades of SCI and the HC group were also discovered. DEIGs were identified, with alteration in some immune-related signaling pathways, vascular endothelial growth factor signaling pathways, and axon guidance signaling pathways. The SCI biomarkers identified and those of American Spinal Injury Society Impairment Scale (AIS) A and AIS D of SCI have certain diagnostic sensitivity. Analysis of the correlation of immune cells and biomarkers showed that biomarkers of SCI, AIS A grade and AIS D grade correlated positively or negatively with some immune cells. CKLF, EDNRB, FCER1G, SORT1, and TNFSF13B can be used as immune biomarkers for SCI. Additionally, GDF11and HSPA1L can be used as biomarkers of SCI AIS A grade; PRKCA and CMTM2 can be used as biomarkers of the SCI AIS D grade. Detecting expression of these putative biomarkers and changes in related immune cells may be helpful for predicting the severity of SCI., 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 © 2023 Li, Liu, Wang, Wang, Zhu, Tang, Wang, Zhou, Gao and Liu.)

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 ( n = 1,030) and 20 ( n = 945) were included. Liquor and total alcohol consumption were associated with a 0.31-year ( P = 0.002) and a 0.12-year ( P = 0.013) greater GrimAge acceleration (GAA) per additional five alcohol years, while beer and wine consumption observed marginal ( P = 0.075) and no associations ( P = 0.359) with GAA, respectively. Any recent binge drinking and the number of days of binge drinking were associated with a 1.38-year ( P < 0.001) and a 0.15-year ( P < 0.001) higher GAA, respectively. We observed statistical interactions between cumulative beer ( P < 0.001) and total alcohol ( P = 0.004) consumption with chronological age, with younger participants exhibiting a higher average in GAA compared to older participants. No associations were observed with the other measures of epigenetic aging. These results suggest cumulative liquor and total alcohol consumption and recent binge drinking may alter age-related epigenetic changes as captured by GAA. With the increasing aging population and widespread consumption of alcohol, these findings may have potential implications for lifestyle modification to promote healthy aging.

Purpose: The increasing incidence of dementia and home-based care exposes family caregivers to a variety of challenges as they endure strong stressors underlying the caregiver role. Despite growing publications on positive aspects of caregiving in dementia, few studies have identified the extent, nature, and gaps in the existing literature based on a holistic view. The aim was to identify key issues and a holistic view of literature regarding positive aspects of caregiving in dementia., Methods: A scoping review was conducted underlying a five-stage framework by Arksey and O'Malley. Five databases, including PubMed, CINAHL, PsycINFO, Embase, and Web of Science, were searched, and references were listed accordingly. Data were extracted by two researchers, comprising article characteristics, forms of positive aspects of caregiving and measurements, theories, forms of dementia and family caregiver, and keywords. Descriptive statistics and narrative synthesis were performed to analyze data. Network analysis of keywords and authors was conducted using VOSviewer software. Word cloud analysis of titles was examined by NVivo., Results: The review included 230 articles, most of which have been published in the last decade (62.61%). Most articles (40.00%) were contributed by the United States. Cross-sectional studies (41.30%) ranked first, followed by qualitative studies (13.48%). Over a quarter of the literature (28.26%) focused on Alzheimer's care, and nearly 90% included all forms of family caregivers. The Positive Aspects of Caregiving Scale and stress coping theory were most frequently cited. Four clusters dominated by Casey D, Quinn C, Joling KJ, and Teahan A were identified in the network of co-authorship. Six themes were identified: current situations of caregiver experiences, antecedents, consequences, measurement development, effects of interventions, and the concept of positive aspects of caregiving. These were in line with network analysis of keywords and word cloud analysis of titles., Conclusions: Positive aspects of caregiving in dementia have been widely concerned, but most of them are based on the theory of the negative stress process and are limited to current situations and influencing factors. Building theories focus on the positive aspects of caregiving, subsequently developing a comprehensive measurement and effective interventions, should be further studied., 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, Li, Liu, Yang, Zhao, Lü and Xiao.)

BACKGROUND We aimed to explore the association between sleep duration and sleep disorder variables obtained from the National Health and Nutrition Examination Survey (NHANES) and stroke. MATERIAL AND METHODS This cross-sectional study enrolled 10 442 participants from the United States. The outcome variable was stroke diagnosed by a doctor. Sleep disorder variables were assessed via self-report questionnaires and included sleep duration, the time required to fall asleep, frequency of sleep deprivation, frequency of early morning wakefulness, and frequency of middle of the night wakefulness. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression models. RESULTS Compared with participants with 6 to 7 h of sleep duration, participants with less than 6 h of sleep duration had an increased risk of stroke of 0.97 times (OR=1.97, 95% CI: 1.19-3.29). Participants with a sleep disorder had 0.71 times (OR=1.71, 95% CI: 1.04-2.82) the risk of stroke than those without a sleep disorder. Stroke was significantly associated with sleep deprivation 16 to 30 times a month (OR=1.99, 95% CI: 1.14-3.46), early morning wakefulness 16 to 30 times a month (OR=1.97, 95% CI: 1.20-3.25), and middle of the night wakefulness 16 to 30 times a month (OR=1.81, 95% CI: 1.05-3.09), compared with no sleep deprivation, early-morning wakefulness, or middle of the night wakefulness. CONCLUSIONS Short sleep duration and sleep disorder were associated with an increased risk of stroke, suggesting healthy sleep behaviors may reduce the risk of stroke. However, further studies are needed to confirm the causality and underlying mechanism.

Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Infections caused by extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are a significant cause of morbidity and health care costs. Globally, the prevailing clonal type is ST131 in association with the bla CTX-M-15 β-lactamase gene. However, other ESBLs, such as bla , can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the United States which carry CTX-M-14 and bla CTX-M-27 , can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the United States which carry bla CTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.

Background & Aims: Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women., Methods: We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs., Results: Later age at menarche was associated inversely with NAFLD (P trend  = .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use P trend  = .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15)., Conclusions: Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nitrogen oxides (NO x ) are a key precursor in O 3 formation. Although stringent anthropogenic NO x emission controls have been implemented since the early 2000s in the United States, several rural regions of California still suffer from O 3 pollution. Previous findings suggest that soils are a dominant source of NO x emissions in California; however, a statewide assessment of the impacts of soil NO x emission (SNO x ) on air quality is still lacking. Here we quantified the contribution of SNO x to the NO x budget and the effects of SNO x on surface O 3 in California during summer by using WRF-Chem with an updated SNO x scheme, the Berkeley Dalhousie Iowa Soil NO Parameterization (BDISNP). The model with BDISNP shows a better agreement with TROPOMI NO 2 columns, giving confidence in the SNO x estimates. We estimate that 40.1% of the state's total NO x emissions in July 2018 are from soils, and SNO x could exceed anthropogenic sources over croplands, which accounts for 50.7% of NO x emissions. Such considerable amounts of SNO x enhance the monthly mean NO 2 columns by 34.7% (53.3%) and surface NO 2 concentrations by 176.5% (114.0%), leading to an additional 23.0% (23.2%) of surface O 3 concentration in California (cropland). Our results highlight the cobenefits of limiting SNO x to help improve air quality and human health in rural California.

Background & Aims: The effect of diurnal variation in energy intake on mortality has not been reported. We investigated the effect of diurnal calorie trajectory on all-cause mortality using data from the National Health and Nutrition Examination Survey (NHANES)., Methods: Participants in the NHANES from 1999 to 2010 were analyzed. We calculated daily energy intake and the two-hourly calorie intake according to dietary interview questionnaires, in which timing of meals, as well as energy and nutritional components of each food were recorded. The daily energy intake and the two-hourly calorie intake were divided by body weight to determine tertiles of daily energy intake and diurnal calorie trajectories, respectively. Three diurnal calorie trajectories (reference group, excess dinner, and high-calorie) were identified. The mortality data were linked to the National Death Index through the end of 2011. Cox proportional hazards models were used to compare the overall mortality among different groups., Results: Among the 14,356 participants included in our analyses, 886 (6.2%) of them died after a median follow-up of 4.4 years. Daily energy intake tertiles were not associated with all-cause mortality in the fully adjusted model. In contrast, high-calorie trajectory was associated with a higher risk of mortality (hazard ratio 3.128, 95% CI 1.175 to 8.330, p = 0.024) compared with the reference group after adjustment for relevant factors., Conclusions: A diurnal high-calorie trajectory was associated with a higher risk of mortality, compared with the reference group. The effect of a large evening meal on mortality merits further investigation., Competing Interests: Conflict of Interest None of the authors had any conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: To investigate the correlation between number of retrieved lymph nodes (rLNs) and prognosis and further ascertain the optimal number of rLNs with a beneficial survival impact in patients with pN0 colon cancer., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched for pN0 colon cancer cases. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal number of rLNs based on the minimal probability (P) value and the largest χ 2 value. Univariate analyses and Cox proportional hazard regression model were used to investigate the relationship between rLN number and overall survival. Multiple analyses were conducted to assess the prognostic predictive ability of the identified optimal rLN cut-off value under different stratifications. Nomograms were established based on the independent prognostic factors selected by the multivariate analysis to predict 3- and 5-year overall survival rates of pN0 patients., Results: A total of 6269 pN0 colon cancer patients who underwent surgical therapy were finally included for analysis. Harvest of at least 18 lymph nodes was determined as the optimal rLN number. This cut-off rLN value (< 18 versus ≥ 18) was identified as an independent prognostic factor (P < 0.001) of overall survival via multivariate analysis. Similar findings were obtained in patients with retrieval of at least 12 lymph nodes (18 > rLNs ≥ 12 versus rLNs ≥ 18) stratified into several groups., Conclusions: The number of rLNs was identified as an independent prognostic factor for pN0 colon cancer. Retrieval of at least 18 lymph nodes was associated with favorable prognosis in patients with pN0 colon cancer, and should, therefore, be regarded as an alternative cut-off value for survival analysis.

Objectives: Primary lung adenosquamous carcinoma (ASC) is a rare cancer subtype and has a poor prognosis. The prognostic factors for resected early-stage ASC remain unclear. We aimed to develop a nomogram to predict lung cancer-specific survival (LCSS) of patients undergoing surgical resection for stage I-II ASC., Methods: Data of patients undergoing resection for stage I-II ASC and diagnosed between 2004-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. All the included patients were randomized at a 7:3 ratio into a training and a validation cohort. We selected and integrated significant prognostic factors based on competing for risk regression to build a nomogram. The performance of the nomogram was evaluated using Harrell's concordance index (C-index) and calibration plots., Results: A total of 988 patients (530 men and 458 women) undergoing surgical resection for stage I-II ASC were identified and randomized into a training (692, 70%) cohort and a validation cohort (296, 30%). The baseline characteristics were similar in the training and validation cohorts. Age, T stage, N stage, and the number of examined lymph nodes were independent prognostic factors for LCSS and were used in the nomogram. The calibration plots showed that the 3- and 5-year LCSS probabilities were consistent between the nomogram prediction and the actual observation. The C-index of the nomogram was 0.671 (95%CI: 0.618-0.724) and 0.635 (95%CI: 0.557-0.713) in the training cohort and validation cohort, respectively. We developed a risk classification system based on the nomogram to stratify patients into high- and low-risk of cancer-specific death groups. Patients with a similar risk shared similar prognostic prediction regardless of the stage category and patients with the same risk shared similar prognoses despite the different stage category., Conclusions: We developed a competing risk nomogram to reliably predict cancer-specific survival of patients undergoing surgical resection for stage I-II ASC. The nomogram might be a useful tool to identify patients undergoing surgical resection for ASC who could be suitable candidates for adjuvant chemotherapy., (© 2020 Wiley Periodicals, Inc.)

Purpose: This study aimed to validate the newly proposed American Joint Committee on Cancer (AJCC) pathological prognostic staging system for young breast cancer patients (aged ≤40 years)., Results: We included 12811 women in this study. Overall, 52.8% of patients in the 7 th AJCC stages were restaged to the 8 th AJCC pathological staging system, including 10.7% upstaged and 42.1% downstaged. The receiver operating characteristics analysis showed that the new staging system had a better role in predicting breast cancer-specific survival (BCSS) compared with 7 th edition staging (P<0.001). The results of the multivariate prognostic analysis showed that the hazard ratio of BCSS increased with the 8 th AJCC stages, while the 7 th anatomic stages had no significant difference in BCSS., Conclusions: The novel pathological staging system could provide more accurate prognostic stratification for young women with breast cancer because of the high proportion of stage migration., Patients and Methods: Data for young breast cancer patients diagnosed between 2010 and 2014 were included from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were applied to statistical analysis.

According to users and places, blood glucose monitoring systems(BGMSs) can be divided into self-monitoring blood glucose test systems(SMBGs) and Point-of-Care Blood Glucose monitoring systems(POC-BGMSs). The Food and Drug Administration(FDA) believes that standards for SMBGs and POC-BGMSs should be different because of different operators, different use environments, different intendance uses and different applicable populations. Now the international standards for evaluating BGMSs include ISO 15197:2013 issued by International Organization for Standardization(ISO), two guidelines on blood glucose monitoring systems issued by FDA, and POCT12-A3 guidelines issued by the American Association for Clinical and Laboratory Standardization(CLSI), ISO standard and FDA guideline-OTC are applicable in SMBGs, CLSI guideline and FDA guideline-POCTI2-A3 are suitable for POC-BGMSs. By analyzing the accuracy evaluation processes of BGMSs based on four standard documents, it is found that the accuracy evaluation of medical BGMSs is more stringent. It is proposed that SMBGs and POC-BGMSs should be supervised separately.

Skin cancer is the most common type of cancer in the United States, the majority of which is caused by overexposure to ultraviolet (UV) irradiance, which is one component of sunlight. National Environmental Public Health Tracking Program at CDC has collaborated with partners to develop and disseminate county-level daily UV irradiance (2005-2015) and total solar irradiance (1991-2012) data for the contiguous United States. UV irradiance dataset was derived from the Ozone Monitoring Instrument (OMI), and solar irradiance was extracted from National Solar Radiation Data Base (NSRDB) and SolarAnywhere data. Firstly, we produced daily population-weighted UV and solar irradiance datasets at the county level. Then the spatial distributions and long-term trends of UV irradiance, solar irradiance and the ratio of UV irradiance to solar irradiance were analyzed. The national average values across all years are 4300 Wh/m 2 , 2700 J/m 2 and 130 mW/m 2 for global horizontal irradiance (GHI), erythemally weighted daily dose of UV irradiance (EDD) and erythemally weighted UV irradiance at local solar noon time (EDR), respectively. Solar, UV irradiances and the ratio of UV to solar irradiance all increased toward the South and in some areas with high altitude, suggesting that using solar irradiance as indicator of UV irradiance in studies covering large geographic regions may bias the true pattern of UV exposure. National annual average daily solar and UV irradiances increased significantly over the years by about 0.3% and 0.5% per year, respectively. Both datasets are available to the public through CDC's Tracking network. The UV irradiance dataset is currently the only publicly-available, spatially-resolved, and long-term UV irradiance dataset covering the contiguous United States. These datasets help us understand the spatial distributions and temporal trends of solar and UV irradiances, and allow for improved characterization of UV and sunlight exposure in future studies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The rarities of primary neuroendocrine prostate cancer (NEPC) and primary adenocarcinoma with neuroendocrine differentiation (NE differentiation) mean that their clinical characteristics have not been fully elucidated., Materials and Methods: A total of 449 patients with NEPC, including 352 cases of pure NEPC and 97 cases of NE differentiation, together with 408 629 cases of prostate adenocarcinoma at diagnosis were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). Clinical parameters and prognoses were compared between patients with different histological types of NEPC using the χ 2 test and Kaplan-Meier analysis, respectively. The prognostic value of prostate-specific antigen (PSA) in NEPC and adenocarcinoma was evaluated using Cox regression and the Kaplan-Meier method., Results: Pure NEPC had higher rates of visceral metastases (brain, lung, and liver: 4.58%, 26.72%, and 36.64%, respectively) but a lower rate of bone metastasis (65.65%) compared with NE differentiation and prostate adenocarcinoma. Moreover, patients diagnosed with pure NEPC had a poorer outcome (median survival time: 10 months) compared with patients with NE differentiation (26 months) and prostate adenocarcinoma (median survival time not reached). Using PSA 4.1 to 10 ng/mL as the reference, the adjusted hazard ratios (HRs) for PSA lower than or equal to 4.0 ng/mL were 2.24 (95% confidence interval [CI]: 1.11-4.55, P = .025) in the NE differentiation group and 1.57 (95% CI: 1.11-2.23, P = .011) in the pure NEPC group., Conclusions: Patients with NE differentiation had different clinical characteristics and a better prognosis than patients with pure NEPC. In addition, low-serum PSA levels were associated with a poorer prognosis in patients with either NEPC or NE differentiation., (© 2019 Wiley Periodicals, Inc.)

Scope: To assess the associations of plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with body fat in a population-based sample and explore the mechanism of action based on browning of white adipose tissue (WAT) in high-fat-diet-induced obese (DIO) mice and 3T3-L1 adipocytes., Methods and Results: Plasma EPA and DHA of 1719 adults in the National Health and Nutrition Examination Survey (2003-2004) are determined by gas chromatography mass spectrometry, while total body fat is measured by dual-energy X-ray absorptiometry. DIO mice are fed a high-fat diet supplemented with EPA or DHA (1% wt/wt) for 15 weeks and 3T3-L1 preadipocytes are treated with EPA or DHA during differentiation. Plasma DHA but not EPA is associated with lower body fat mass (p trend < 0.0001), which persists in overweight/obese subjects (p trend = 0.02). DHA supplementation reduces inguinal WAT and exhibits a more pronounced thermogenic effect than EPA in DIO mice. In vitro, the browning process is induced after 2-day and 6-day treatment with DHA and EPA, respectively., Conclusion: Plasma DHA but not EPA is inversely associated with body fat mass. The more potent anti-adipogenic effect of DHA than EPA may involve a better capability of inducing browning of WAT for DHA., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Whether dietary fish consumption is linked to mortality remains unclear. We aim to investigate the association of fish consumption with mortality in Chinese and US nationwide populations., Methods and Results: We utilize data from China Health and Nutrition Survey (CHNS, n = 14 117) and National Health and Nutrition Examination Survey (NHANES, n = 33 221) including NHANES III conducted in 1988-1994 and continuous NHANES 1999-2010. Cox proportional hazards regression is used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 14 and 9.8 years for CHNS and NHANES, 1007 and 5209 deaths are documented, respectively. Among Chinese adults, increased fish intake is significantly associated with decreased total mortality. The multivariable-adjusted HRs (95% CIs) across increasing categories of fish intake are 0.45 (0.36-0.56), 0.72 (0.60-0.86), and 0.70 (0.59-0.85) (p trend < 0.0001). However, fish intake is not associated with total mortality among US adults (p trend = 0.21). We only detected a borderline inverse association between fish intake and stroke mortality (p trend = 0.05), whereas a positive association with diabetes mortality in the third category of fish intake in NHANES., Conclusion: In these two nationwide cohort studies, fish consumption is associated with a reduced risk of total mortality for Chinese but not US populations., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Youth development programs represent key tools in the work of youth-serving practitioners and researchers who strive to promote character development and other attributes of youth thriving, particularly among youth who may confront structural and social challenges related to their racial, ethnic, and/or economic backgrounds. This article conducts secondary analyses of two previously reported studies of a relatively recent innovation in Boy Scouts of America (BSA) developed for youth from low-income communities, Scoutreach. Our goal is to provide descriptive and admittedly preliminary exploratory information about whether these data sets-one involving a sample of 266 youth of color from socioeconomically impoverished communities in Philadelphia (M age  = 10.54 years, SD = 1.58 years) and the other involving a pilot investigation of 32 youth of color from similar socioeconomic backgrounds in Boston (M age  = 9.97 years, SD = 2.46 years)-provide evidence for a link between program participation and a key indicator of positive development; that is, character development. Across the two data sets, quantitative and qualitative evidence suggested the presence of character development among Scoutreach participants. Limitations of both studies are discussed and implications for future longitudinal research are presented. We suggest that future longitudinal research should test the hypothesis that emotional engagement is key to creating the conditions wherein Scoutreach participation is linked to character development.

In epidemiologic studies, alcohol consumption appears more strongly associated with risk of estrogen receptor (ER)-positive than ER-negative breast cancer. However, this association has not been assessed by other potentially relevant tumor markers, such as androgen receptor (AR) or insulin receptor (IR). In the prospective Nurses' Health Study cohort, we evaluated alcohol consumption and breast cancer risk by individual tumor marker expression (i.e., ER, progesterone receptor [PR], AR, and IR) while controlling for other markers and also assessed the joint effect of these receptors. During 26 years follow-up of 106,037 women, 2552 invasive breast cancers contributed to the analysis. When all four markers were considered simultaneously, no significant heterogeneity of the alcohol and breast cancer association was observed by any of the markers. However, each increment in one drink per day was associated with 10% (95% confidence interval [CI] = 4%, 15%) and 9% (95% CI = 4%, 15%) increased risk of AR-positive and ER-positive breast cancer, respectively, while no increased risk was observed among AR-negative or ER-negative tumors. The association was independent of PR and IR expression. Assessment of the joint expression of hormone receptors revealed a significantly increased risk among AR+/ER+/PR+ (hazard ratio [HR] per drink/day = 1.11, 95% CI = 1.06, 1.17) but not in other subgroups (e.g. , AR-/ER-/PR-: HR = 0.99; 95% CI = 0.88, 1.12). Our data suggest that the alcohol and breast cancer association may be more pronounced among ER-positive and/or AR-positive breast tumors. However, our data do not support an important role of IR in the association.

Youth development programs, such as the Boy Scouts of America, aim to develop positive attributes in youth (e.g., character virtues, prosocial behaviors, and positive civic actions), which are necessary for individuals and societies to flourish. However, few developmental studies have focused on how specific positive attributes develop through participation in programs such as the Boy Scouts of America. As part of the Character and Merit Project, this article examined the developmental trajectories of character and other positive attributes, which are of focal concern of the Boy Scouts of America and the developmental literature. Data were collected from 1398 Scouts (M = 8.59 years, SD = 1.29 years, Range 6.17-11.92 years) and 325 non-Scout boys (M = 9.06 years, SD = 1.43 years, Range 6.20-11.81 years) over five waves of testing across a two-and-half-year period. Latent growth-curve analyses of self-report survey data examined the developmental trajectories of the attributes. Older youth rated themselves lower than younger participants on helpfulness, reverence, thriftiness, and school performance. However, all youth had moderately high self-ratings on all the attributes. Across waves, Scouts' self-ratings increased significantly for cheerfulness, helpfulness, kindness, obedience, trustworthiness, and hopeful future expectations. Non-Scout boys' self-ratings showed no significant change for any attributes except for a significant decrease in religious reverence among non-Scout boys from religious institutions. We discuss implications for positive youth development and for the role of the Boy Scouts of America programming in character development.

Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in local-regional recurrence (LRR), disease-specific survival (DSS) or overall survival (OS) for sentinel lymph node dissection (SLND) and completion axillary lymph node dissection (ALND) among patients undergoing breast-conserving therapy for clinical T1-T2, N0 breast cancer with 1 or 2 positive SLNs. However, Only 7% of study participants had invasive lobular carcinoma (ILC). Because ILC has a different pattern of metastases, frequently presenting as small foci requiring immunohistochemistry for detection, the applicability of ACOSOG Z0011 trial data to ILC patients is unclear., Study Design: We identified all ILC patients in the Surveillance, Epidemiology, and End Results (SEER) database (1998-2009) who met the ACOSOG Z0011 eligibility criteria. Patients were evaluated on the basis of the extent of axillary surgery (SLND alone or ALND), and the clinical outcomes of these 2 groups were compared., Results: 1269 patients (393 SLND and 876 ALND) were identified from the SEER database. At a median follow-up time of 71 months, there were no differences in OS or disease-specific survival between the two groups., Conclusion: SLND alone may result in outcomes comparable to those achieved with ALND for patients with early-stage ILC who meet the ACOSOG Z0011 eligibility criteria.

Objective: To assess long-term effects of biofeedback training on pubertal chronic prostatitis (CP)., Methods: Pubertal CP patients received 12-week intensive biofeedback training and were divided into two groups: group 1 received further monthly training ≥ 24 (26-36) months; group 2 received further monthly training <24 (13-23) months. National Institutes of Health-CP Symptom Index (NIH-CPSI) scores, maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) were recorded monthly., Results: Total NIH-CPSI scores decreased significantly in group 1 (n = 10; mean age ± SD 16.5 ± 1.1 years) together with all subdomain scores (pain, urination, life impact). Total NIH-CPSI scores increased significantly in group 2 (n = 12; mean age ± SD 16.3 ± 1.2 years) at 30 and 36 months, and were significantly different from group 1 at these time points. Urination and life-impact scores increased significantly and Qmax decreased significantly in group 2 at 30 and 36 months. PVR was unchanged in either group., Conclusions: Twelve-week intensive biofeedback training requires lengthy consolidation sessions to achieve long-term success. Further investigation should assess longer intervals between consolidation sessions, for improving patient compliance and outcome.

The problem for assessing biosimilarity and drug interchangeability of follow-on biologics (biosimilar products) is studied. Unlike the generic products, the development of biosimilar products is much more complicated because of fundamental differences in functional structures and manufacturing processes. As a result, the criteria and standard methods for the design and analysis of bioequivalence assessment of generic drug products may not be directly applicable to assessing biosimilarity of biosimilar products. In this article, we provide some scientific considerations for criteria, design, and analysis regarding the assessment of biosimilarity and drug interchangeability of biosimilar products. In addition, we discuss scientific and practical issues raised at the 2010 FDA public hearing and the 2011 FDA public meeting on biosimilar products., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Because TNF-α polymorphisms that increase TNF-α production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk., Methods: We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure., Results: Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results., Conclusions: We found no evidence of a role for household endotoxin in NHL etiology.

Aims: Duck enteritis virus (DEV) is a member of the family Herpesviridae, the genome of which is not completely analyzed. In order to provide further insights into the genomic organization, we decided to amplify the unknown sequence in the US region since three key glycoproteins are coded in this region. Glycoprotein D encoded by US6 gene is essential for virus entry and plays an important role in protecting animals from lethal challenge. Glycoprotein I and E encoded by US7 and US8 gene are required for cell-to-cell spread., Methods: Single oligonucleotide nested polymerase chain reaction was adopted to amplify the unknown sequence. The open reading frames (ORF) were predicted by Editseq program. Then the sequence was submitted to an online program to search promoter, polyadenylation signal and potential N-glycosylation sites. The phylogenetic analysis was performed by MEGA4.1, while multiple alignments were performed by ClustalX., Results: Three complete ORFs including US6, US7 and US8 were determined. The three genes shared the same polyadenylation signal. Phylogenetic analysis showed that DEV was closed to mardivirus of alphaherpesvirus., Conclusion: These results extend our understanding of the DEV genome and its classification, and also provide further basic knowledge for functional investigations on the proteins in the US region., (2010 S. Karger AG, Basel.)

The authentication of foods is an important aspect of quality control and food safety. Honey is one of the most natural and most popular foods in the world. A fast and reliable method to determine the geographical origin of honey was developed based on fingerprinting and barcoding of proteins in honey by using matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS) and MALDI Biotyper 1.1 software, respectively. The protein mass spectra of 16 honey samples of known Hawaii origin were obtained and peak information was extracted to generate protein fingerprints. This information was transformed into a database library of spectral barcodes that were used for differentiation of the geographical origin of honeys based on pattern matching. The differentiation ability of the database library of barcodes was validated by comparing the results of replicate assays of 5 of the 16 honey samples of known Hawaii origin obtained directly from the producers. Validation results showed that the protein fingerprints of honeys have better comparability with those honeys in the library known to be from the same region than with those of honey samples from other regions. The protein fingerprints were used to differentiate the geographical origins of commercially purchased honey samples with labels indicating that they were produced in different countries and various states of the USA, including Hawaii. The results showed that the MALDI TOF MS Biotyper system can be a rapid, simple and practical method for determining the geographical origin of honeys sold in commerce.

Rationale: In 1989, the United States embarked upon an ambitious path to eliminate tuberculosis (TB) nationwide. Although incidence rates of TB disease in the United States are declining, these cases represent only a tiny fraction of all TB infections. Understanding national trends in TB infection may be important in anticipating future trends in TB disease., Objectives: Describe the epidemiology of Mycobacterium tuberculosis infection in the United States in 1971-1972 and 1999-2000., Methods: We studied nationally representative cohorts of the U.S. noninstitutionalized civilian population participating in the 1971-1972 and 1999-2000 National Health and Nutrition Examination Surveys. Participants were tuberculin skin tested and the epidemiology of TB infection was compared across surveys. Logistic regression was used to identify associations between participant and household characteristics and TB infection., Measurements and Main Results: In 1999-2000, 4.2% (95% confidence interval [CI], 3.3-5.2%) of the U.S. population aged 1 year or older displayed evidence of TB infection. Among persons aged 25-74, the prevalence of infection decreased from 14.4% in 1971-1972 (95% CI, 11.6-17.7%) to 5.6% in 1999-2000 (95% CI, 4.4-7.1%). Declines in the relative burden of infection among persons aged 25-74 were greater in the United States-born population (12.6 to 2.5%) compared with the nation's foreign-born population (35.9 to 21.3%)., Conclusions: The United States has experienced a substantial decline in the burden of TB infection since the early 1970s. Despite this, the prevalence of infection among the nation's foreign-born population is over eight times greater than that observed in the United States-born population.

Rationale: The prevalence of pulmonary nontuberculous mycobacterial (NTM) infections in the United States appears to be rising, but it is unclear if this is due to enhanced detection or actual increases in the burden of infection. Temporal changes in the epidemiology of Mycobacterium intracellulare sensitization may help explain recently observed trends in pulmonary NTM infections., Objectives: Describe the epidemiology of M. intracellulare sensitization in the United States in 1971-1972 and 1999-2000., Methods: We studied nationally representative cohorts of the United States' noninstitutionalized civilian population participating in the 1971-1972 and 1999-2000 National Health and Nutrition Examination Surveys (NHANES). Participants were skin tested with M. intracellulare antigen and sensitization prevalence was compared across NHANES surveys and between participant subgroups. Logistic regression was used to identify associations between participant characteristics, environmental factors, and NTM sensitization., Measurements and Main Results: The 1971-1972 and 1999-2000 NHANES cohorts included 1,490 and 7,384 individuals, respectively. Between 1971-1972 and 1999-2000, the prevalence of M. intracellulare sensitization increased from 11.2% (95% confidence interval, 9.2-13.5%) to 16.6% (95% confidence interval, 13.2-20.6%). On multivariate analysis of the 1999-2000 cohort, age, sex, race, birthplace, education, and occupation were strongly associated with M. intracellulare sensitization., Conclusions: In 1999-2000, an estimated one in six persons in the United States demonstrated M. intracellulare sensitization, up from one in nine persons in 1971-1972. The observed rising prevalence of sensitization is consistent with observed increases in the rates of pulmonary NTM infections in the United States.