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This research aimed to determine the impact of the effectiveness in the application of an independent method of teaching students on their progress in achieving a certain level of Japanese. The study used key methods that implied the experimental involvement of 60 3rd- and 4th-year American and Chinese students with the N3 and N2 levels of Japanese to pass a simplified version of the international JLPT (Japanese Language Proficiency Test) after applying the autonomy learning methodology. The analysis and processing of the experimental exam results were performed using the Microsoft Excel program and derivation of the average statistical percentage of the number of points scored at each stage of the N3 and N2 exams. The results of the study and the test scores led to the conclusion that the most difficult tasks for American students are those in writing and reading. On the other hand, Chinese students have difficulties in listening and speaking Japanese over linguistic phonetic differences and complex grammar compared to Chinese. Referring to the N2 group of American and Chinese students, their scores are somewhat equal due to the total complexity of this level, which requires utmost care for all four skills of foreign language learning. The present findings can serve as auxiliary material for the educational sphere in terms of an individual approach in autonomy learning to more effectively study Japanese and obtain positive results when passing the JLPT test.

Bacteria and fungi possess distinct physiological traits. Their macroecology is vital for ecosystem functioning such as carbon cycling. However, bacterial and fungal biogeography and underlying mechanisms remain elusive. In this study, we investigated bacterial versus fungal macroecology by integrating a microbial‐explicit model—CLM‐Microbe—with measured fungal (FBC) and bacterial biomass carbon (BBC) from 34 NEON sites. The distribution of FBC, BBC, and FBC: BBC (F:B) ratio was well simulated across sites, with variations in 99% (P < 0.001), 97% (P < 0.001), and 99% (P < 0.001) being explained by the CLM‐Microbe model, respectively. We found stronger biogeographic patterns of FBC relative to BBC across the United States. Fungal and bacterial turnover rates showed similar trends along latitude. However, latitudinal trends of their component fluxes (carbon assimilation, respiration, and necromass production) were distinct between bacteria and fungi, with those latitudinal trends following inverse unimodal patterns for fungi and showing exponential declining responses for bacteria. Carbon assimilation was dominated by vegetation productivity, and respiration was dominated by mean annual temperature for bacteria and fungi. The dominant factor for their necromass production differs, with edaphic factors controlling fungal and mean annual temperature controlling bacterial processes. The understanding of fungal and bacterial macroecology is an important step toward linking microbial metabolism and soil biogeochemical processes. Distinct fungal and bacterial macroecology contributes to the microbial ecology, particularly on microbial community structure and its association with ecosystem carbon cycling across space. Key Points: We investigated the macroecology of biomass carbon and turnover for fungi and bacteria in natural ecosystems across the United StatesFungi show stronger biogeographic patterns in biomass carbon than bacteriaEdaphic properties dominate fungal necromass formation, while mean annual temperature controls bacterial necromass formation across sites [ABSTRACT FROM AUTHOR]

Introduction: Lupus nephritis (LN) treatment aims to control and prevent flares and irreversible kidney damage. Around 30% of patients are unresponsive to treatment; however, real-world LN treatment patterns have not been reported. Objectives of this retrospective cohort study (GSK 209758) were to quantify the time to switching/re-initiating induction therapy in patients with LN initiating immunosuppressant therapy and conversion from induction to maintenance immunosuppressant therapy, and to assess corticosteroid use. Methods: Patients with LN initiating induction or maintenance immunosuppressant therapy were identified using claims data. Patients were followed up from the index date (immunosuppressant initiation date) until treatment discontinuation, death, disenrollment, administrative censoring, or the end of follow-up period. The cumulative incidence of switching/re-initiating induction therapy and conversion to maintenance therapy was estimated using outpatient pharmacy claims and procedure codes. Corticosteroid use was estimated using pharmacy claims; a mean daily dose of ≥ 7.5 mg/day was considered high. Results: In total, 5000 patients with LN contributed 5516 treatment episodes (induction cohort, N = 372; maintenance cohort, N = 5144). In the induction cohort, the cumulative incidence (95% confidence interval) of switching between induction therapies was 24.6% (20.1–30.0) at 12 months, while 59.6% (52.4–66.1) of patients converted to maintenance therapy at 12 months. In the maintenance cohort, 21.2% (19.9–22.5) re-initiated induction therapy at 12 months. Oral corticosteroid use decreased during the follow-up in both cohorts, but 21.5% of patients remained on a high dose at 12 months in the induction cohort, while 15.8% in the maintenance cohort were taking a high dose at 24 months. Conclusions: Around a quarter of patients with LN initiating immunosuppressant therapy switched within 12 months, while a fifth re-initiated induction therapy within 12 months. Use of high corticosteroid doses were observed during 24 months of follow-up. These data suggest that many patients do not respond to existing standard LN therapies. [ABSTRACT FROM AUTHOR]

Over 16 million children have been detected positive for the coronavirus disease 2019 (COVID-19) in the United States since the outbreak of the pandemic. In general, children infected with severe acute respiratory syndrome coronavirus type 2 tend to have lighter symptoms than adults. However, in some cases, the infection can develop into severe forms, such as multisystem inflammatory syndrome in children. Moreover, long-term public health preventive interventions have had some negative effects on the physical and mental health of children. Given the important role that vaccination plays in reducing severe illness and mortality, it is essential for the efficient implementation of vaccination in the pediatric population. Nevertheless, parental distrust of vaccination, especially with regard to its safety and efficacy, hinders this process. Herein, we comprehensively summarize the available data on the safety and effectiveness of COVID-19 vaccine in children. The results show that the currently approved COVID-19 vaccine is safe and effective for children. Although two doses of vaccine in children seem insufficient to prevent Omicron infection, the booster dose provides enhanced protection against infection and severe illness. Most importantly, the bivalent vaccine has been approved for use in the pediatric population to extend the immune response to currently circulating Omicron variant. And the immune protection afforded to newborns after maternal vaccination appears to last only 6 months. Therefore, in the current situation where the rate of virus mutation is accelerating and the COVID-19 pandemic is still severe, it is crucial to extend vaccine protection to children over 6 months of age to weave a tighter safety net. [ABSTRACT FROM AUTHOR]

Introduction: The spatiotemporal patterns of Corona Virus Disease 2019 (COVID-19) is detected in the United States, which shows temperature difference (TD) with cumulative hysteresis effect significantly changes the daily new confirmed cases after eliminating the interference of population density. Methodology: The nonlinear feature of updated cases is captured through Generalized Additive Mixed Model (GAMM) with threshold points; Exposure-response curve suggests that daily confirmed cases is changed at the different stages of TD according to the threshold points of piecewise function, which traces out the rule of updated cases under different meteorological condition. Results: Our results show that the confirmed cases decreased by 0.390% (95% CI: -0.478~ -0.302) for increasing each one degree of TD if TD is less than 11.5°C; It will increase by 0.302% (95% CI: 0.215 ~ 0.388) for every 1°C increase in the TD (lag0-4) at the interval [11.5, 16]; Meanwhile the number of newly confirmed COVID-19 cases will increase by 0.321% (95% CI: 0.142 ~ 0.499) for every 1°C increase in the TD (lag0-4) when the TD (lag0-4) is over 16°C, and the most fluctuation occurred on Sunday. The results of the sensitivity analysis confirmed our model robust. Conclusions: In US, this interval effect of TD reminds us that it is urgent to control the spread and infection of COVID-19 when TD becomes greater in autumn and the ongoing winter. [ABSTRACT FROM AUTHOR]

Background: The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March 2020. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. The risk factors associated with county-level mortality of COVID-19 with various levels of prevalence are not well understood. Methods: Using the data obtained from the County Health Rankings and Roadmaps program, this study applied a negative binomial design to the county-level mortality counts of COVID-19 as of August 27, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-varying cumulative confirmed cases from March 1 to August 27, 2020. COVID-19 patients were not analyzed individually but were aggregated at the county-level, where the county-level deaths of COVID-19 confirmed by the local health agencies. Clustering analysis and Kruskal–Wallis tests were used in our statistical analysis. Results: A total of 3125 infected counties were assigned into three classes corresponding to low, median, and high prevalence levels of infection. Several risk factors were significantly associated with the mortality counts of COVID-19, where higher level of air pollution (0.153, P < 0.001) increased the mortality in the low prevalence counties and elder individuals were more vulnerable in both the median (0.049, P < 0.001) and high (0.114, P < 0.001) prevalence counties. The segregation between non-Whites and Whites (low: 0.015, P < 0.001; median:0.025, P < 0.001; high: 0.019, P = 0.005) and higher Hispanic population (low and median: 0.020, P < 0.001; high: 0.014, P = 0.009) had higher likelihood of risk of the deaths in all infected counties. Conclusions: The mortality of COVID-19 depended on sex, race/ethnicity, and outdoor environment. The increasing awareness of the impact of these significant factors may help decision makers, the public health officials, and the general public better control the risk of pandemic, particularly in the reduction in the mortality of COVID-19. [ABSTRACT FROM AUTHOR]

This study examines the impact of changing the tone of a traditional syllabus to make it more learner-centered. The researchers examined a required wellness course that serves over 8,000 students per year at a large, four-year public university in the southern United States. Concerns about student progression through programs and graduation rates had prompted a number of faculty to look into ways to increase these numbers. The investigators changed the tone of the syllabus to determine if a more learner-centered document would increase the chances of students interacting with the syllabus and, in turn, increase the success rates in the course. The results indicated that few students spent sufficient time reading the syllabus to take in all the information regardless of the tone used within the document, so the tone, by itself, did not impact student success. [ABSTRACT FROM AUTHOR]

A new risk measure fully based on historical data is proposed, from which we can naturally derive concentrated optimal portfolios rather than imposing cardinality constraints. The new risk measure can be expressed as a quadratics of the introduced greedy matrix, which takes investors' joint behavior into account. We construct distribution-free portfolio selection models in simple case and realistic case, respectively. The latest techniques for describing transaction cost constraints and solving nonconvex quadratic programs are utilized to obtain the optimal portfolio efficiently. In order to show the practicality, efficiency, and robustness of our new risk measure and corresponding portfolio selection models, a series of empirical studies are carried out with trading data from advanced stock markets and emerging stock markets. Different performance indicators are adopted to comprehensively compare results obtained under our new models with those obtained under the mean-variance, mean-semivariance, and mean-conditional value-at-risk models. Out-of-sample results sufficiently show that our models outperform the others and provide a simple and practical approach for choosing concentrated, efficient, and robust portfolios. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate health care resource use and direct medical costs attributable to herpes zoster (HZ) among elderly residents of skilled nursing facilities (SNF). Methods: This was a retrospective matched cohort study using data from 300 SNF in the United States. A total of 404 patients with HZ were matched with 1616 patients with no documented HZ or post-herpetic neuralgia using propensity scores. The study period included a 1-month pre-index period and the 90-day acute/subacute phase following the HZ index date. Health care resource utilization was captured from the long term care minimum dataset (MDS) and SNF admission-discharge records. The direct medical costs consisted of the SNF net bed revenue and hospitalization cost. Results: Over the 4-month study period, significantly more patients were hospitalized among the HZ (20.5%) than non-HZ cohort (14.4%). Both the numbers of hospitalization episodes and hospitalization days were greater for HZ than for non-HZ patients. An average additional 0.09 hospitalization episodes and 0.55 days of hospitalization were estimated in a multivariate model for patients in the HZ compared with the non-HZ cohort. The incremental direct medical costs, which are composed of the incremental medical costs incurred in the SNF, and the incremental costs attributable to hospitalization, were estimated between $1079 and $1673 for patients with HZ. Conclusion: In the SNF setting, the presence of HZ imposes significant health care resource utilization and direct medical costs. [Copyright &y& Elsevier]

When facing a multi-period defined contribution (DC) pension plan investment problem during the accumulation phase, the risk aversion attitude of a mean-variance investor may depend on state variables. In this paper, we propose a state-dependent risk aversion model which is a linear function of the current wealth level after contribution. This risk aversion model is reasonable from both the dimensional analysis and the economic point of view. Moreover, we incorporate the wage income factor into our model. In the field of dynamic investment analysis, most studies have irrational situations in their models because of the lack of the positiveness for the wealth process. In view of it, we further improve the work of Wang and Chen by completely eliminating the irrationality of the model. Due to the time-inconsistency of the resulting stochastic control problem, we derive the explicit expressions of the equilibrium control and the corresponding equilibrium value function by adopting the game theoretic framework developed in Björk and Murgoci. Further, two special cases are discussed. Finally, using a more realistic risk aversion coefficient, we provide a series of empirical tests based on the real data from the American market and compare our results with the relevant results in the literature. [ABSTRACT FROM AUTHOR]

Little is known about the associations between dietary aromatic amino acids (AAAs) intake and mortality from all causes and cardiovascular disease (CVD). Accordingly, we evaluated these associations in the adult population of the United States using data from the Third National Health and Nutrition Examination Survey. This was a cohort study. Dietary intake of AAAs (tyrosine, phenylalanine, and tryptophan) was determined from the total nutrient intake document. We hypothesized that higher dietary AAA intake would lower all-cause and CVD mortality in adults in the United States. First, we categorized participants into quintiles based on their dietary intakes of total AAAs, tyrosine, phenylalanine, and tryptophan. Then, we established 4 Cox proportional-hazards models (models 1-4) and calculated hazard ratios and 95% confidence intervals to estimate the associations between dietary intakes of total AAAs, tyrosine, phenylalanine, and tryptophan and all-cause and CVD mortality. Mortality status was primarily obtained from files linked to the National Death Index records up to December 31, 2015. After multivariate adjustment, the hazard ratios (95% confidence intervals) of CVD mortality in the highest quintiles of dietary total AAAs, tyrosine, phenylalanine, and tryptophan intake (reference: the lowest quintiles) were 0.66 (0.52-0.84), 0.65 (0.51-0.83), 0.66 (0.52-0.85) and 0.64 (0.50-0.82), respectively. In a nationally representative cohort, higher dietary intakes of total AAA and the 3 individual AAAs were independently associated with a lower risk of CVD mortality, and these associations were stronger in non-Hispanic White people than in other people. Our study showed higher dietary intake of aromatic amino acids (including tyrosine, phenylalanine, and tryptophan) could lower risk of CVD mortality in adult participants (n ≥ 18) in NHANES III. NHANES, Third National Health and Nutrition Examination Survey. [Display omitted] [ABSTRACT FROM AUTHOR]

The article focuses on a study which investigated demographic and clinical predictors of midurethral sling failure in women with stress urinary incontinence (SUI). The study found that overall odds of midurethral sling failure are more common with women with previous incontinence surgery, more severe urinary incontinence symptoms, and urethral hypomobility. Pad weight testing was also considered to be a powerful predictor of midurethal sling failure.

Background: Abnormalities in lipid metabolism are common among adult asthmatics. However, the precise directionality linking asthma to blood lipid levels remains controversial. Our study aimed to evaluate the association between the Non-HDL to HDL Ratio (NHHR), a lipid composite index, and asthma prevalence among the adult population in the United States., Methods: Utilizing adult participants' data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2018, the study employed a multivariable logistic regression model, adjusting for covariables, to establish the relationship between NHHR levels and the prevalence of asthma. Furthermore, smoothing curve fitting and subgroup analyses were conducted to investigate the robustness of this association., Results: This study included 26,023 adult individuals (mean age = 49.63 ± 17.66). In the fully adjusted model, a significant inverse association was observed between log-transformed NHHR values and asthma prevalence (OR = 0.85, 95% CI: 0.79-0.93). Subgroup analysis revealed that gender served as a modulator, altering the association between NHHR levels and asthma prevalence. A more pronounced negative association between lnNHHR and asthma prevalence was noted among male participants [(Male: OR = 0.78, 95% CI: 0.69-0.88) vs. (Female: OR = 0.92, 95% CI: 0.83-1.03), P for interaction = 0.0313]., Conclusions: Our study revealed an inverse association between NHHR levels and the prevalence of asthma in the US adult population, which is influenced by gender. NHHR measurement may be a potential tool for early identification and prediction of adult asthmatics in specific populations., (© 2024. The Author(s).)

Objective: The purpose of this study was to investigate the association between depressive symptoms and second primary cancer (SPC) in U.S. cancer survivors., Methods: Cancer survivors from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study, and depressive symptoms were defined by the Patient Health Questionnaire 9 (PHQ-9). The association between depressive symptoms and SPC was assessed via multiple logistic regression, restricted cubic spline (RCS), sensitivity, and subgroup analyses., Results: This study involved 2315 participants representing >15 million noninstitutionalized U.S. residents. Multivariate logistic regression fully adjusted for confounders revealed that cancer survivors with a PHQ-9 score ≥ 10 had a greater risk of developing SPC than those with a PHQ-9 score of 0-4 ([OR] = 1.88, 95% [CI] = 1.20-2.89, p = 0.005). The RCS showed a linear positive correlation between the PHQ-9 score and SPC (p for overall = 0.017). The robustness of this association was subsequently confirmed via multiple interpolation of missing data and different cluster-level methods (namely weighted linear regression) as sensitivity analyses. Furthermore, subgroup analyses confirmed this correlation was stronger in participants with sleep duration <7 h (p for interaction = 0.036)., Conclusion: Moderate to severe depressive symptoms in cancer survivors were associated with an increased risk of developing SPC, especially at <7 h of sleep., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial., Aim: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System., Method: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19., Results: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time., Conclusion: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Little is known regarding the association between weight change and accelerated aging., Objectives: This study aimed to estimate the influence of weight change across adulthood on biological aging acceleration in middle-aged and older adults in the United States., Methods: We used data of 5553 adults (40-84 y) from the National Health and Nutrition Examination Survey 1999-2010. Weight change patterns (i.e., stable normal, maximal overweight, obese to nonobese, nonobese to obese, and stable obese) and absolute weight change groups across adulthood (i.e., from young to middle adulthood, young to late adulthood, and middle to late adulthood) were defined. A biological aging measure (i.e., phenotypic age acceleration [PhenoAgeAccel]) at late adulthood was calculated. Survey analysis procedures with the survey weights were performed., Results: Across adulthood, maximal overweight, nonobese to obese, and stable obesity were consistently associated with higher PhenoAgeAccel. For instance, from young to middle adulthood, compared with participants who had stable normal weight, participants experiencing maximal overweight, moving from the nonobese to obese, and maintaining obesity had 1.71 (standard error [SE], 0.21; P < 0.001), 3.62 (SE, 0.28; P < 0.001), and 6.61 (SE, 0.58; P < 0.001) higher PhenoAgeAccel values, respectively. From young to middle adulthood, relative to absolute weight loss or gain of <2.5 kg, weight loss of ≥2.5 kg was marginally associated with lower PhenoAgeAccel (P = 0.054), whereas an obese to nonobese pattern from middle to late adulthood was associated with higher PhenoAgeAccel (P < 0.001)., Conclusions: Maximal overweight, nonobese to obese, and stable obesity across adulthood, as well as an obese to nonobese pattern from middle to late adulthood, were associated with accelerated biological aging. In contrast, weight loss from young to middle adulthood was associated with decelerated biological aging. The findings highlight the potential role of weight management across adulthood for aging. Monitoring weight fluctuation may help identify the population at high risk of accelerated aging., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: One Health is an emerging research area that has received increasing attention globally. In this study, we aimed to explore the global research trend and hotspots of One Health and provide a reference for potential future research and practices., Methods: This was a bibliometric descriptive study of publications on One Health in four directions, including zoonotic diseases, antimicrobial resistance, food safety, and vector-borne infections. Publications from 2003 to 2021 were retrieved using the Scopus database on One Health, which were screened based on the PRISMA guidelines. Keywords were analyzed and visualized using VOSviewer software., Results: A total of 12,815 publications were included. The annual number of publications and those on each topic showed a gradual increase from 181 in 2003 to 1,647 in 2020, with an average annual growth rate of about 20.2%; the top three countries in terms of the number of publications were the United States of America (n=3,588), the United Kingdom (n=1,429) and China (n=1,233); the major research subjects were mainly in the natural sciences, with fewer social sciences subjects involved ( n = 312; 1%). The main research directions within the area of zoonotic diseases included viral, bacterial, parasitic zoonotic diseases, and vector-borne diseases, with a small amount of antimicrobial resistance research. The major research interests within antimicrobial resistance were Enterobacteriaceae drug-resistant bacteria, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa , and antimicrobial resistance gene detection; research on food safety clustered around agronomy research, aquaculture research as well as a small amount of antimicrobial resistance research in food; and research on vector-borne diseases focused on mosquito-borne infectious diseases, tick-borne infectious diseases, and vectors., Conclusions: The scientific literature on One Health has witnessed a rising global trend. Most research has focused on the human-animal health interface, while environmental health is often neglected. Research subjects mainly fall within natural science disciplines, with less social science research. More support needs to be given to interdisciplinary and intersectoral cooperation and research in the future., 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 Miao, Li, Ding, Lu, Pan, Guo, Zhou and Wang.)

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59-3.46), 3.16 (2.68-3.73), and 5.39 (4.63-6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15-5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09-6.94), and compared with remdesivir (3.85; 3.03-4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The spatiotemporal patterns of Corona Virus Disease 2019 (COVID-19) is detected in the United States, which shows temperature difference (TD) with cumulative hysteresis effect significantly changes the daily new confirmed cases after eliminating the interference of population density., Methodology: The nonlinear feature of updated cases is captured through Generalized Additive Mixed Model (GAMM) with threshold points; Exposure-response curve suggests that daily confirmed cases is changed at the different stages of TD according to the threshold points of piecewise function, which traces out the rule of updated cases under different meteorological condition., Results: Our results show that the confirmed cases decreased by 0.390% (95% CI: -0.478 ~ -0.302) for increasing each one degree of TD if TD is less than 11.5°C; It will increase by 0.302% (95% CI: 0.215 ~ 0.388) for every 1°C increase in the TD (lag0-4) at the interval [11.5, 16]; Meanwhile the number of newly confirmed COVID-19 cases will increase by 0.321% (95% CI: 0.142 ~ 0.499) for every 1°C increase in the TD (lag0-4) when the TD (lag0-4) is over 16°C, and the most fluctuation occurred on Sunday. The results of the sensitivity analysis confirmed our model robust., Conclusions: In US, this interval effect of TD reminds us that it is urgent to control the spread and infection of COVID-19 when TD becomes greater in autumn and the ongoing winter., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Yongmei Ding, Liyuan Gao, Ning-Yi Shao.)

Importance: The self-perception of weight and weight loss attempts might promote weight loss and maintenance., Objective: To examine trends in current measured body mass index (BMI) and weight, self-reported weight, self-perceived weight status, weight loss attempts, and weight loss strategies among adults in the United States., Design, Setting, and Participants: This national cross-sectional study used data from continuous National Health and Nutrition Examination Survey (NHANES) data sets (1999-2000 to 2015-2016). Participants were US residents older than 20 years. Data were analyzed from January 2018 to December 2018., Main Outcomes and Measures: Current measured BMI and weight, self-reported weight, self-perceived weight status, weight loss attempts, and applied weight loss strategies. Adjusted, self-reported, prior-year weight was calculated using correction equations that considered age, sex, race/ethnicity, and quartile of self-reported prior-year weight., Results: Data were collected from 48 026 participants (19 792 [41.2%] aged 40-64 years; 24 255 [50.5%] women; 21 725 [45.2%] white) through 9 surveys from 1999-2000 to 2015-2016. Increasing trends were observed in current measured BMI (difference, 1.20; 95% CI, 0.92-1.47; P for trend < .001), current measured weight (difference 2.77 kg; 95% CI, 1.92-3.61 kg; P for trend < .001), adjusted, self-reported, prior-year weight (difference, 2.36 kg; 95% CI, 1.52-3.21 kg; P for trend < .001), and the difference between measured and adjusted self-reported weight (difference 0.70 kg; 95% CI, 0.34-1.07 kg; P for trend < .001). During this period, the proportion of overall participants who had attempted to lose weight increased from 34.3% to 42.2% (difference, 8.0%; 95% CI, 4.1%-10.5%; P for trend < .001). The most commonly reported weight loss strategies with the most rapidly increasing prevalence during the study period were reduced food consumption (21.2%-31.9%; difference, 11.1%; 95% CI, 8.2%-13.3%; P for trend < .001), exercise (18.2%-31.5%; difference, 14.4%; 95% CI, 11.3%-16.9%; P for trend < .001), and frequent water intake (0.2%-26.3%; difference, 26.2%; 95% CI, 24.1%-29.0%; P for trend < .001). Between 2005-2006 and 2015-2016, increases were also observed for the reported consumption of more fruits, vegetables, and salads (0.1%-29.4%; difference, 30.3%; 95% CI, 28.1%-31.2%; P for trend < .001), changing eating habits (0.3%-20.5%; difference, 20.2%; 95% CI, 19.1%-22.3%; P for trend < .001), and the consumption of less sugar, candy, and sweets (0.2%-20.9%; difference, 21.7%; 95% CI, 19.3%-22.6%; P for trend < .001)., Conclusions and Relevance: In this cross-sectional study, our data indicated an increasing trend in the proportion of participants who attempted to lose weight and a parallel increasing trend in current measured BMI and weight among adults in the United States.

Importance: The American Heart Association (AHA) introduced the Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health. However, several shortcomings of these metrics have been identified. Therefore, a revised set of LS7 metrics was developed., Objectives: To evaluate national trends in the metrics addressed by the revised LS7 and the individual and combined associations of the revised LS7 metrics with all-cause and cause-specific mortality and to compare these measures with the AHA recommended LS7 metrics., Design, Setting, and Participants: This national cross-sectional study used data from the National Health and Nutrition Examination Survey from 1988 to 2016. The revised LS7 metrics included a combination of the body mass index and waist to hip ratio, Healthy Eating Index-2010, and a lower blood pressure threshold of greater than or equal to 130/80 mm Hg in addition to physical activity, smoking, total cholesterol, and fasting blood glucose. Data for this study were analyzed from June 1, 2017, to December 31, 2017., Main Outcomes and Measures: The primary outcome was all-cause mortality. The secondary outcome was cancer and cardiovascular disease (CVD) mortality., Results: Data were available for 13 606 adults in 1988 to 1994 (7329 [53%] female; mean [SD] age, 47 [17.7] years), 6360 in 1999 to 2004 (3442 [54%] female; mean [SD] age, 47 [18.6] years), 10 618 in 2005 to 2010 (5428 [51%] female; mean [SD] age, 47 [17.5] years), and 10 773 in 2011 to 2016 (5474 [50%] female; mean [SD] age, 48 [17.4] years). Compared with a revised LS7 score of 0 to 1, the adjusted hazard ratios for a revised LS7 score of 5 to 7 were 0.46 (95% CI, 0.35-0.61) for all-cause mortality, 0.42 (95% CI, 0.25-0.68) for cancer mortality, and 0.37 (95% CI, 0.24-0.55) for CVD mortality, respectively. The adjusted hazard ratios for participants who met 6 or more AHA recommended ideal LS7 metrics were 0.49 (95% CI, 0.33-0.74) for all-cause mortality, 0.60 (95% CI, 0.29-1.25) for cancer mortality, and 0.24 (95% CI, 0.13-0.47) for CVD mortality. Participants with a body mass index of 29.9 or less but without central obesity were independently associated with lower risk of all-cause and CVD mortality. Blood pressure was associated with 36.7% or more of the observed population-attributable fraction of mortality., Conclusions and Relevance: The individual revised LS7 metrics with modified criteria regarding weight, blood pressure, and diet provide more information about factors associated with cancer mortality than the original AHA LS7 metrics.

MYCN amplification in neuroblastoma predicts poor prognosis and resistance to therapy. Yet pharmacological strategies of direct MYC inhibition remain unsuccessful due to its "undruggable" protein structure. We herein developed a synthetic lethal screen against MYCN-amplified neuroblastomas using clinically approved therapeutic reagents. We performed a high-throughput screen, from a library of 938 FDA-approved drugs, for candidates that elicit synthetic lethal effects in MYC-driven neuroblastoma cells. The proteasome inhibitors, which are FDA approved for the first-line treatment of multiple myeloma, emerge as top hits to elicit MYC-mediated synthetic lethality. Proteasome inhibition activates the PERK-eIF2α-ATF4 axis in MYC-transformed cells and induces BAX-mediated apoptosis through ATF4-dependent NOXA and TRIB3 induction. A combination screen reveals the proteasome inhibitor bortezomib (BTZ) and the histone deacetylase (HDAC) inhibitor vorinostat (SAHA) concertedly induce dramatic cell death in part through synergistic activation of BAX. This combination causes marked tumor suppression in vivo, supporting dual proteasome/HDAC inhibition as a potential therapeutic approach for MYC-driven cancers. This FDA-approved drug screen with in vivo validation thus provides a rationale for clinical evaluation of bortezomib, alone or in combination with vorinostat, in MYC-driven neuroblastoma patients.

Purpose: To evaluate how the monitoring and treatment for diabetic macular edema (DME) has changed in a national sample., Design: Retrospective cohort study., Setting: Administrative medical claims data from a large, national U.S. insurer., Study Population: Beneficiaries of a U.S. insurance company., Observation Procedures: All incident cases of DME were found. Those in years 2002/3, 2006 and 2010 were followed for a 2-year observation period and those from 2009, 2010 and 2011 for a 1-year observation period., Main Outcome Measures: Types and frequencies of treatment were tallied and compared over each of the cohorts., Results: Two-year cohorts had 233, 251 and 756 patients in 2002/3, 2006 and 2010 respectively. One-year cohorts had 1002, 1119 and 1382 patients in 2009, 2010 and 2011, respectively. Both percentage of patients receiving therapy and number of treatments given increased across the 2-year cohorts for both focal laser and anti-vascular endothelial growth factor (anti-VEGF) (p<0.001). The highest use of anti-VEGF agents in any of the cohorts was in the 2011 1-year group that only averaged 3.78 injections. Focal laser was used 2.5x as frequently as anti-VEGF injections in the most recent cohorts with only a high of 14.0% of DME patients receiving anti-VEGF therapy in any of the cohorts., Conclusion: Regardless of treatment modality (laser or injection) DME patients received vastly fewer treatments than patients in randomized control trials. Despite the proven superior visual outcomes of anti-VEGF agents over focal laser in DME, focal laser was still used more frequently.

Importance: Fluoroquinolones are the most commonly prescribed antibiotic class in the outpatient setting. Recent reports have implicated an association between oral fluoroquinolones and an increased risk of uveitis., Objective: To determine the hazard of uveitis with oral fluoroquinolone use., Design, Setting, and Participants: A retrospective cohort study was conducted using medical claims data from a large national US insurer (N = 4,387,651). Cohorts from ambulatory care centers across the United States were created including every new user of an oral fluoroquinolone or β-lactam antibiotic prescription with at least 24 months of data prior to the date of the prescription from January 1, 2000, to January 30, 2013. Exclusion criteria consisted of any previous diagnosis of uveitis or a uveitis-associated systemic illness. Participants were censored for a new diagnosis of a uveitis-associated systemic illness, the end of an observation period, use of the other class of antibiotic, or removal from the insurance plan. Data analysis was performed from January 2 through March 15, 2015., Main Outcomes and Measures: The hazard of a uveitis diagnosis after a fluoroquinolone prescription compared with a β-lactam prescription using multivariate regression with Cox proportional hazards models., Results: Of the 4,387,651 patients in the database, 843,854 individuals receiving a fluoroquinolone and 3,543,797 patients receiving a β-lactam were included in the analysis. After controlling for age, race, and sex using multivariate analysis, no hazard for developing uveitis at the 30-, 60-, or 90-day observation windows was seen (hazard ratio [HR] range, 0.96; 95% CI, 0.82-1.13; to 1.05; 95% CI, 0.95-1.16; P > .38 for all comparisons). The 365-day observation period showed a small increase in the HR for the fluoroquinolone cohort (1.11; 95% CI, 1.05-1.17; P < .001). Moxifloxacin produced an increased hazard for uveitis at every time point (HR range, 1.47-1.75; 95% CI, 1.27-2.37; P < .001 for all comparisons). Secondary analysis demonstrated a similar hazard at 365 days for a later diagnosis of a uveitis-associated systemic illness after fluoroquinolone use (HR range, 1.46-1.96; 95% CI, 1.42-2.07; P < .001 for all comparisons)., Conclusions and Relevance: These data do not support an association between oral fluoroquinolone use and uveitis. Instead, this study shows an association between oral fluoroquinolone use and the risk for uveitis-associated systemic illnesses, which is a possible source of bias that could explain the findings of previous studies.

Importance: Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab., Objective: To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer., Design, Setting, and Participants: A retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015., Main Outcomes and Measures: The odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab., Results: In total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11)., Conclusions and Relevance: The results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary.

Cardiac arrhythmias are a complication of myocarditis. There are no large studies of in-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. This was a retrospective 2-center review of patients ≤21 years hospitalized with acute myocarditis from 1996 to 2012. Fulminant myocarditis was defined as the need for inotropic support within 24 hours of presentation. Acute arrhythmias occurred at presentation and subacute after admission. Eighty-five patients (59% men) presented at a median age of 10 years (1 day to 18 years). Arrhythmias occurred in 38 patients (45%): 16 acute, 12 subacute, and 9 acute and subacute (1 onset unknown). Arrhythmias were associated with low voltages on the electrocardiogram (14 of 34, 41% vs 6 of 47, 13%; odds ratio [OR] 4.78, 95% confidence interval [CI] 1.60 to 14.31) and worse outcome (mechanical support, orthotopic heart transplant, or death; OR 7.59, 95% CI 2.61 to 22.07) but were not statistically significantly associated with a fulminant course, ST changes, initial myocardial function, lactate, creatinine level, C-reactive protein and/or erythrocyte sedimentation rate, or troponin I level, after adjusting for multiple comparisons. Subacute arrhythmias were associated with preceding ST changes (10 of 15, 67% vs 15 of 59, 25%, OR 5.87, 95% CI 1.73 to 19.93). All patients surviving to discharge had arrhythmia resolution or control before discharge (10 on antiarrhythmic), with 1 exception (patient with complete heart block requiring a pacemaker). At 1-year follow-up, there were 3 recurrences of ventricular arrhythmias, but no arrhythmia-related mortality. In conclusion, arrhythmias are common in pediatric patients with myocarditis, occurring in nearly 1/2 of all hospitalized children and are associated with a worse outcome. Early identification of subacute arrhythmias using electrocardiographic changes may help management. A majority of patients do not require continued postdischarge arrhythmia treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Hypoactive sexual desire disorder (HSDD) is a multifactorial disorder that is affected by, and may affect, mental health. Data are from the HSDD Registry for Women, a large multicenter observational study of US women with clinically diagnosed generalized, acquired HSDD. We analyzed complete baseline data from 1088 premenopausal women., Methods: Validated measures of sexual function and distress, physical and mental health, and depression symptoms were obtained from participant and clinician questionnaires. Depression was defined as having a current diagnosis, symptoms (by Patient Health Questionnaire), or use of antidepressant (AD) medication., Results: Thirty-four percent met criteria for current depression, of whom 56% took AD medication. Depressed women were less happy with their relationship, had greater difficulty forming or maintaining relationships, and decreased partnered sex compared with nondepressed HSDD patients. Sexual function was significantly lower in women with current depression (p < .001) versus nondepressed women. Among AD users, those with inadequately treated depression had increased severity of HSDD (p = .02) and reduced sexual desire (p = .04) compared with women in remission. Otherwise, AD use was not associated with sexual function differences among women with HSDD and diagnosed depression., Conclusions: About one third of premenopausal women with HSDD presented with current symptoms or a diagnosis of depression. Women with HSDD and depression reported poorer relationships and sexual function compared with women with HSDD and no depression. AD use was associated with sexual dysfunction only among women with unresolved symptoms of depression, and conversely, current symptoms of depression were associated with more severe HSDD among AD users.

Sexual desire and arousal difficulties are often correlated in women. However, no studies have examined characteristics of women with clinically diagnosed hypoactive sexual desire disorder (HSDD) that increase the likelihood of co-occurring arousal difficulties. The authors examined combined HSDD and arousal/ lubrication problems using baseline cross-sectional data from the HSDD Registry for Women. Their analyses were restricted to women who could be classified with certainty as having arousal or lubrication difficulties by the Female Sexual Function Index (requiring sexually activity in the past 4 weeks). Results showed that among 426 premenopausal women with HSDD, 50.2% had arousal problems, 42.5% lubrication problems, 39.0% combination, and 46.2% neither. Among 174 postmenopausal women, prevalence percentages were 58.0% arousal, 56.9% lubrication, 49.4% combined, and 34.5% neither. The strongest predictor of combined arousal/lubrication problems was self-reported severity of HSDD. Among premenopausal women, race/ethnicity, depression, and lower relationship happiness were also associated with combined arousal/lubrication problems. Among postmenopausal women, surgical menopause and use of selective serotonin reuptake inhibitors were positively associated with arousal problems. Arousal and lubrication problems were present in approximately half of this subsample of HSDD Registry participants, with distinctions in prevalence and predictors by menopausal status and type of arousal difficulty (arousal vs. lubrication).

Background: Major depressive disorder (MDD) is a common illness that affects ∼7% of adults in the United States each year. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine that has demonstrated efficacy and tolerability in the treatment of MDD., Objective: The purpose of our study was to examine dosing patterns and pretreatment predictors of high-dose duloxetine therapy for patients with MDD in the usual clinical setting., Methods: Data were from 6132 commercially insured patients with MDD initiated on duloxetine during 2005 and 2006. Patients had no duloxetine use in the previous 6 months and had continuous enrollment in a health plan for the 12 months immediately preceding and following initiation. Dosing patterns and predictors of high-dose therapy with duloxetine were examined., Results: Initial doses of duloxetine were <60 mg/d, 60 mg/d, 90 mg/d, and ≥120 mg/d for 32.4%, 60.9%, 3.1%, and 3.5% of patients, respectively. Maximum daily doses were <60 mg, 60 mg, 90 mg, and ≥120 mg for 16.3%, 59.3%, 11.0%, and 13.3% of patients, respectively. Patients treated with >60 mg/d for at least 2 months were older, were more likely to have been treated by a psychiatrist, had greater comorbidity, and had used more health care resources and psychotropic and pain medications in the previous year. The following factors were independently associated with doses of >60 mg/d: older age (odds ratio [OR] = 1.33-1.46); comorbid neuropathic pain (OR = 1.88); fibromyalgia (OR = 1.36); dysthymic disorder (OR = 1.24); prior injury/poisoning (OR = 1.19); physician specialty (psychiatrist, OR = 1.55); and prior use of psychostimulants (OR = 1.26), benzodiazepines (OR = 1.19), venlafaxine (OR = 1.35), or atypical antipsychotics (OR = 1.35)., Conclusions: Most of the commercially insured patients in this dataset were initiated and maintained on a duloxetine dose of 60 mg/d. Although the data are limited in their generalizability, the characteristics associated with higher dose therapy describe a complex group of patients who may require more intensive drug treatment and monitoring., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Aims: Determine whether urodynamic measures of urethral function [(valsalva leak point pressure (VLPP), maximum urethral closure pressure (MUCP), functional urethral length (FUL)] and the results of the supine empty bladder stress test (SEBST) correlate with each other and with subjective and objective measures of urinary incontinence (UI)., Methods: Data were collected preoperatively from subjects enrolled in a multicenter surgical trial of mid-urethral slings. Subjective measures included questionnaire scores from the Medical Epidemiological and Social Aspects of Aging Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Objective measures included a 24-hr pad weight test, incontinence episode frequency on a 3-day voiding diary, and a SEBST., Results: Five hundred ninety-seven women enrolled. Three hundred seventy-two women had valid VLPP values; 539 had valid MUCP/FUL values. Subjective measures of severity had weak to moderate correlation with each other (r = 0.25-0.43) and with objective measures of severity (r = -0.06 to 0.45). VLPP and MUCP had moderate correlation with each other (r = 0.36,  P< 0.001). Urodynamic measures of urethral function had little or no correlation with subjective or objective measures of severity. Subjects with a positive SEBST had more subjective and objective severity measures compared to the negative SEBST group, but they did not have significantly different VLPP and MUCP values., Conclusions: VLPP and MUCP have moderate correlation with each other, but each had little or no correlation with subjective or objective measures of severity or with the results of the SEBST. This data suggests that the urodynamic measures of urethral function are not related to subjective or objective measures of UI severity., (© 2010 Wiley-Liss, Inc.)

Objectives: We sought to compare the burden of hospitalizations associated with rotavirus gastroenteritis (RGE) in children younger than 5 years in US Medicaid and non-Medicaid populations in 2000 and 2003., Methods: We used the Kids' Inpatient Database (KID) to examine the burden of RGE-associated hospitalizations in terms of numbers and rates of hospitalizations, lengths of stay, and hospital charges. Two indirect methods were also used to estimate RGE-associated hospitalizations, because rotavirus testing is not routinely performed., Results: Approximately 40% of children younger than 5 years were enrolled in Medicaid in 2003, but this population accounted for nearly 50% of all RGE-associated hospitalizations and 60% of total charges. Children enrolled in Medicaid had significantly greater hospitalization rates, average lengths of stay, and average charges per stay than did those not enrolled., Conclusions: Although RGE affects all socioeconomic groups, the Medicaid population accounted for a disproportionate number of the hospitalizations. With the inclusion of rotavirus vaccines in the pediatric immunization schedule, it is important that US children, especially those enrolled in Medicaid programs, are vaccinated to reduce the burden of RGE.