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Power split configurations exhibit potential on decreasing fuel consumption. However, how to select the best power split configuration among all the possible configurations still need to be explored. In this paper, a one-dimensional searching ECMS (Equivalent Consumption Minimization Strategy) is developed to evaluate fuel consumption for input power split configuration. Additionally, a battery degradation model based on experimental data is applied to evaluate the battery degradation for input power split configuration. According to one-dimensional searching ECMS and battery degradation model, the impact of different input power split configurations on fuel consumption and battery degradation is investigated. Simulations show that configuration T1 has fuel consumption and battery degradation advantages for PHEV city bus application in China. These advantages are observed because the system efficiency operation points of configuration T1 are closer to the high efficiency area than the system efficiency operation points of other input power split configurations. Furthermore, according to the lever model and one-dimensional searching ECMS method, a power split configuration selection method is provided in this paper. The simulation results based on configuration selection method still indicate that configuration T1 appears to have the best fuel economy for PHEV city bus application. Moreover, configuration T5, with a lever length close to 0, exhibits the worst fuel consumption and battery degradation. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of deaths in cancer patients in the United States. Identification of new molecular targets is clearly needed to improve therapeutic outcomes of this devastating human disease. Activating mutations in K-Ras oncogene and increased expression of FOXM1 protein are associated with poor prognosis in patients with non-small-cell lung cancer. Transgenic expression of activated KrasG12D in mouse respiratory epithelium is sufficient to induce lung adenocarcinomas; however, transcriptional mechanisms regulated by K-Ras during the initiation of lung cancer remain poorly understood. Foxm1 transcription factor, a downstream target of K-Ras, stimulates cellular proliferation during embryogenesis, organ repair and tumor growth, but its role in tumor initiation is unknown. In the present study, we used transgenic mice expressing KrasG12D under control of Sftpc promoter to demonstrate that Foxm1 was induced in type II epithelial cells before the formation of lung tumors. Conditional deletion of Foxm1 from KrasG12D-expressing respiratory epithelium prevented the initiation of lung tumors in vivo. The loss of Foxm1 inhibited expression of K-Ras target genes critical for the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, including Ikbkb, Nfkb1, Nfkb2, Rela, Jnk1, N-Myc, Pttg1 and Cdkn2a. Transgenic overexpression of activated FOXM1 mutant was sufficient to induce expression of these genes in alveolar type II cells. FOXM1 directly bound to promoter regions of Ikbkb, Nfkb2, N-Myc, Pttg1 and Cdkn2a, indicating that these genes are direct FOXM1 targets. FOXM1 is required for K-Ras-mediated lung tumorigenesis by activating genes critical for the NF-κB and JNK pathways. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of deaths in cancer patients in the United States. Identification of new molecular targets is clearly needed to improve therapeutic outcomes of this devastating human disease. Activating mutations in K-Ras oncogene and increased expression of FOXM1 protein are associated with poor prognosis in patients with non-small-cell lung cancer. Transgenic expression of activated KrasG12D in mouse respiratory epithelium is sufficient to induce lung adenocarcinomas; however, transcriptional mechanisms regulated by K-Ras during the initiation of lung cancer remain poorly understood. Foxm1 transcription factor, a downstream target of K-Ras, stimulates cellular proliferation during embryogenesis, organ repair and tumor growth, but its role in tumor initiation is unknown. In the present study, we used transgenic mice expressing KrasG12D under control of Sftpc promoter to demonstrate that Foxm1 was induced in type II epithelial cells before the formation of lung tumors. Conditional deletion of Foxm1 from KrasG12D-expressing respiratory epithelium prevented the initiation of lung tumors in vivo. The loss of Foxm1 inhibited expression of K-Ras target genes critical for the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, including Ikbkb, Nfkb1, Nfkb2, Rela, Jnk1, N-Myc, Pttg1 and Cdkn2a. Transgenic overexpression of activated FOXM1 mutant was sufficient to induce expression of these genes in alveolar type II cells. FOXM1 directly bound to promoter regions of Ikbkb, Nfkb2, N-Myc, Pttg1 and Cdkn2a, indicating that these genes are direct FOXM1 targets. FOXM1 is required for K-Ras-mediated lung tumorigenesis by activating genes critical for the NF-κB and JNK pathways. [ABSTRACT FROM AUTHOR]

Context: Neurofilament light chains (sNFLs) increase in patients with diabetes (DM) and are associated with death., Objective: This work aimed to examine whether sNFL mediates associations of DM with all-cause mortality and the extent of interaction or joint relations of sNFL and DM with mortality., Methods: This population-based cohort study was conducted using the 2013 to 2014 cycle of the National Health and Nutrition Examination Survey. A total of 2071 adults aged 20 to 75 years with sNFL measurements were included. sNFL was lg-transformed (LgNfl). Participants were included whose LgNfl was higher than 1.48 pg/mL or who were diagnosed with DM. All-cause mortality was the primary outcome obtained through linkage to registries., Results: During a median follow-up of 6.1years, 85 participants died. Incidence rates (per 1000 person-years [95% CI]) of all-cause mortality were 27.78 (19.98∼35.58) in adults with LgNfl greater than 1.48 pg/mL and DM, 9.01 (1.99∼16.03) in adults with LgNfl greater than 1.48 pg/mL but no DM, 3.07 (1.01∼5.13) in adults with DM and LgNfl less than or equal to 1.48 pg/mL, and 2.21 (1.15∼3.27) in adults without DM and LgNfl less than or equal to 1.48 pg/mL. Significant interaction but not mediation was observed between LgNfl and DM. Compared with adults without DM and LgNfl less than or equal to 1.48 pg/mL, those with DM and LgNfl greater than 1.48 pg/mL had higher risks of all-cause mortality (hazard ratio; 95% CI, 7.06; 3.52∼14.16)., Conclusion: In general US adults with DM, elevated sNFLs were associated with higher all-cause mortality specifically, supporting an important role of sNFLs in predicting health outcome in individuals with DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Human health is commonly threatened by organophosphorus pesticides (OPPs) due to their widespread use and biological characteristics. However, the combined effect of mixtures of OPPs metabolites on the risk of hypertension and potential mechanism remain limited., Objectives: To comprehensively investigate the effects between OPPs exposure on hypertension risk and explore and underlying mechanism among US general population., Methods: This cross-sectional study collected US adults who had available data on urine OPPs metabolites (dialkyl phosphate compounds, DAPs) from the National Health and Nutrition Examination Survey (NHANES) to assess the relationships of DAPs with hypertension risk. Survey-weighted logistic regression, restricted cubic spline (RCS), and mixed exposure analysis models [weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR)] were used to analyze individual, dose-response and combined associations between urinary DAPs metabolites and hypertension risk, respectively. Mediation analysis determined the potential intermediary role of serum albumin and liver function in the above associations., Results: Compared with the reference group, participants with the highest tertile levels of DEP, DMTP, DETP, and DMDTP experienced increased risk of hypertension by 1.21-fold (95%CI: 1.02-1.36), 1.20-fold (95%CI: 1.02-1.42), 1.19-fold (95%CI: 1.01-1.40), and 1.17-fold (95%CI: 1.03-1.43), respectively. RCS curve also showed positive exposure-response associations of individual DAPs with hypertension risk. WQS and BKMR analysis further confirmed DAP mixtures were significantly associated with increased risk of hypertension, with DEP identified as a major contributor to the combined effect. Mediation analysis indicated that serum albumin and AST/ALT ratios played crucial mediating roles in the relationships between individual and mixed urinary DAPs and the prevalence of hypertension., Conclusion: Our findings provided more comprehensive and novel perspectives into the individual and combined effects of urinary OPPs matabolites on the increased risk of hypertension and the possible driving mechanism, which would be of great significance for environmental control and early prevention of hypertension., 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 © 2024 Elsevier B.V. All rights reserved.)

Fish consumption is a major route of human exposure to mercury (Hg), yet limited understanding of how anthropogenic activities drive geographic variations in fish Hg worldwide hinders effective Hg pollution management. Here we characterized global geographic variations in total Hg (THg) and methylmercury (MeHg), compared THg and MeHg levels between the United States and China, and used a structural equation model to link the geographic variability of MeHg in fish to human activities. Despite previously reported higher Hg emissions in China, Chinese fish have lower THg and MeHg levels than fish in the United States owing to a lower trophic magnification slope, shortened food chains and shorter fish lifespans. The structural equation model revealed strong impacts of human activities on MeHg levels in fish. In the future, China may face elevated MeHg levels in fish with the ongoing recovery of food web ecology, highlighting the importance of local policies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Cell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs., Methods: Related regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan's Pharmaceuticals and Medical Device Agency, South Korea's Ministry of Food and Drug Safety, and the National Medical Products Administration of China., Results: Compared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance., Conclusions: This study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China's future learning and development in this field., (© 2024. The Author(s).)

Objective: Insufficient or prolonged sleep each day may contribute to the onset of cardiovascular disease and diabetes, and there may be some variability between genders; however, current research evidence is limited. We aimed to investigate the effects of gender on self-reported sleep duration and the prevalence of cardiovascular disease and diabetes., Research Design and Methods: This study is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults obtained from the National Health and Nutrition Examination Survey (NHANES) (2005-2020), and 13,002 participants, including 6,774men and 6,228women, were obtained by excluding the missing values for each variable self-reported sleep duration data obtained by using a habitual baseline questionnaire. Logistic regression models investigated the associations between gender-specific self-reported sleep duration, CVDs, and diabetes events., Result: In all participants, respectively, compared with sleep 7-8 h/day, the multivariable-adjusted odds ratios significantly associated with < 7 h /day and > 8 h /day were (1.43[1.15, 1.78]) and (1.34[1.01, 1.76]) for CHF, (1.62[1.28, 2.06]) for Angina, (1.42[1.17, 1.71]) for heart attack, (1.38[1.13, 1.70]) and (1.54[1.20, 1.97]) for Stroke, (1.21[1.09, 1.35]) and (1.28[1.11, 1.48]) for diabetes. In men, CHF (1.67[1.21, 2.14]), Angina (1.66[1.18, 2.15]), Stroke (1.55[1.13,1.97]), and diabetes (1.15[1.00, 1.32]) were significantly associated with < 7 h /day, and stroke (1.73[1.16, 2.32]) and diabetes (1.32[1.06, 1.52]) were significantly associated with > 8 h /day. In women, angina(1.83[1.16, 2.50]), heart attack(1.63[1.11, 2.15]), and diabetes (1.32[1.11, 1.54]) were significantly associated with < 7 h /day, while diabetes (1.31[1.03, 1.59]) was significantly associated with > 8 h /day., Conclusion: Self-reported long and short sleep duration was independently associated with partial CVDs and diabetes risk. However, sleep duration and gender did not have multiplicative or additive interactions with the onset of diabetes and CVDs., (© 2024. The Author(s).)

Objective: Breast cancer is the most common cancer in women, threatening both physical and mental health. The epidemiological evidence for association between sleep duration, depression and breast cancer is inconsistent. The aim of this study was to determine the association between them and build machine-learning algorithms to predict breast cancer., Methods: A total of 1,789 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the study, and 263 breast cancer patients were identified. Sleep duration was collected using a standardized questionnaire, and the Nine-item Patient Health Questionnaire (PHQ-9) was used to assess depression. Logistic regression yielded multivariable-adjusted breast cancer odds ratios (OR) and 95% confidence intervals (CI) for sleep duration and depression. Then, six machine learning algorithms, including AdaBoost, random forest, Boost tree, artificial neural network, limit gradient enhancement and support vector machine, were used to predict the development of breast cancer and find out the best algorithm., Results: Body mass index (BMI), race and smoking were statistically different between breast cancer and non-breast cancer groups. Participants with depression were associated with breast cancer (OR = 1.99, 95%CI: 1.55-3.51). Compared with 7-9h of sleep, the ORs for <7 and >9 h of sleep were 1.25 (95% CI: 0.85-1.37) and 1.05 (95% CI: 0.95-1.15), respectively. The AdaBoost model outperformed other machine learning algorithms and predicted well for breast cancer, with an area under curve (AUC) of 0.84 (95%CI: 0.81-0.87)., Conclusions: No significant association was observed between sleep duration and breast cancer, and participants with depression were associated with an increased risk for breast cancer. This finding provides new clues into the relationship between breast cancer and depression and sleep duration, and provides potential evidence for subsequent studies of pathological mechanisms.

Objectives: The weight-adjusted waist circumference index (WWI), a novel obesity indicator, gives better accuracy in assessing both muscle and fat mass. Our goal was to evaluate the relationship between WWI and the occurrence of hyperuricemia/gout among middle-aged and older adults in America., Methods: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2007-2014 cycles. Logistic regression analyses, subgroup analyses, and restricted cubic splines (RCS) were performed to evaluate the association between WWI and hyperuricemia/gout prevalence., Results: A total of 5332 adults aged 50 years and above were included in this study. The prevalence of hyperuricemia and gout was 23.20% and 6.70% respectively. The fourth quartile of WWI was associated with a 56% higher risk for hyperuricemia, compared with the first quartile (OR = 1.56, 95% CI 1.07-2.27, P trend < 0.001). A similar association was found between continuous WWI increase and OR of hyperuricemia in the fully adjusted model (OR = 1.35, 95% CI = 1.13-1.61, P < 0.05). However, WWI was not significantly associated with the prevalence of gout. The RCS model suggested a significant linear relationship between WWI and the risk of hyperuricemia/gout. Stratification analysis showed that the positive associations of WWI with the risk of hyperuricemia were more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia., Conclusions: Our findings suggest a positive correlation between WWI and hyperuricemia among middle-aged and older adults in America. Employing WWI as a tool for hyperuricemia prevention may be meaningful. Key Points • Weight-adjusted waist circumference index is a new obesity evaluation index. • Weight-adjusted waist circumference index is associated with hyperuricemia not gout. • The association is more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

This study investigated the relationship between A body shape index (ABSI) and bone mineral density (BMD) in older Americans and found a negative linear association, which was particularly pronounced in diabetic population. An early focus on ABSI in the elderly population will help in the prevention of osteoporosis., Objective: A body shape index (ABSI) is an abdominal obesity index developed based on epidemiological statistics and high ABSI indicates that waist circumference (WC) is higher than expected for a given height and weight and corresponds to a more central concentration of body volume. The objective of this study was to determine whether there is a linear or nonlinear relationship between ABSI and total femur bone mineral density (BMD) in older Americans and whether the relationship between the ABSI and total femur BMD varies across populations., Methods: This cross-sectional study was based on data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). Weighted multiple linear regression, restricted cubic spline (RCS) curves, subgroup analysis, and interaction tests were used to examine the association between ABSI and total femur BMD., Results: This study included 2505 older adults. This study found a negative linear correlation between ABSI and total femur BMD (β = -3.2, 95%CI: -5.0, -1.4, p < 0.001). When participants were grouped according to quartiles of ABSI, those in the upper quartile had lower total femur BMD compared to those in the bottom quartile of ABSI. This negative association remained consistent across gender, age, education level, smoking, physical activity and BMI subgroups. However, in the diabetes subgroup, ABSI showed a stronger negative association with total femur BMD., Conclusions: The study shows a negative linear association between ABSI and total femur BMD in older Americans, with this negative association being stronger in the diabetic population., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: To investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures., Methods: In this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression., Results: In this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m 2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89-0.98]), DEP (OR = 0.94 [95% CI: 0.90-0.99]), DMTP (OR = 0.91 [95% CI: 0.86-0.95]), and DETP (OR = 0.85 [95% CI: 0.80-0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects., Conclusion: Together, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity., (© 2024. The Author(s).)

NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep disorders remains unknown.; A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2016. The association between NHHR and sleep disorders was explored using weighted multivariate logistic regression and generalized summation models. Subgroup analyses were employed to verify the robustness of this association. The prevalence of sleep disorders was 25.83% in a total of 22,221 participants. Compared to the lowest quartile of NHHR, participants in the top quartile had a 14% higher odds of sleep disorders prevalence in fully adjusted model (OR: 1.14, 95% CI: 1.06-1.23). After subgroup analyses and interaction tests, sex, race, marital status, education level, body mass index (BMI), person income ratio (PIR), alcohol consumption, smoking status, hypertension, and diabetes mellitus were not significantly associated with this positive association (P for interaction > 0.05). The NHHR is positively associated with sleep disorders in US adults. The management and monitoring of NHHR may have a potential role in improving sleep disorders., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests that sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including kidney failure. The mechanisms underlying these associations remain poorly understood. We used proteomic profiling to gain insight into the pathobiology of sickle cell trait., Methods: We measured proteomics ( N =1285 proteins assayed by Olink Explore) using baseline plasma samples from 592 Black participants with sickle cell trait and 1:1 age-matched Black participants without sickle cell trait from the prospective Women's Health Initiative cohort. Age-adjusted linear regression was used to assess the association between protein levels and sickle cell trait., Results: In age-adjusted models, 35 proteins were significantly associated with sickle cell trait after correction for multiple testing. Several of the sickle cell trait-protein associations were replicated in Black participants from two independent cohorts (Atherosclerosis Risk in Communities study and Jackson Heart Study) assayed using an orthogonal aptamer-based proteomic platform (SomaScan). Many of the validated sickle cell trait-associated proteins are known biomarkers of kidney function or injury ( e.g. , hepatitis A virus cellular receptor 1 [HAVCR1]/kidney injury molecule-1 [KIM-1], uromodulin [UMOD], ephrins), related to red cell physiology or hemolysis (erythropoietin [EPO], heme oxygenase 1 [HMOX1], and α -hemoglobin stabilizing protein) and/or inflammation (fractalkine, C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 [MCP-1], and urokinase plasminogen activator surface receptor [PLAUR]). A protein risk score constructed from the top sickle cell trait-associated biomarkers was associated with incident kidney failure among those with sickle cell trait during Women's Health Initiative follow-up (odds ratio, 1.32; 95% confidence interval, 1.10 to 1.58)., Conclusions: We identified and replicated the association of sickle cell trait with a number of plasma proteins related to hemolysis, kidney injury, and inflammation., (Copyright © 2023 by the American Society of Nephrology.)

Main Objective: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic., Study Design and Methods: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission., Results and Significance: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months., Conclusions: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528)., Competing Interests: The authors have declared that no competing interests exist.

The need for palliative care (PC) has gained increased attention during the COVID-19 pandemic. Palliative care adds an extra layer of support and care for patients with advanced chronic illnesses and their families. Because of pandemic restrictions, access and provision of PC services were challenging and resulted in huge suffering and caregiving burden among patients with advanced chronic illnesses and their families, especially those living in smaller towns and rural communities. The study aimed to describe the impact of COVID-19 on PC services and examine various ethical, moral, and practice issues and challenges experienced by rural providers. Using a community-based participatory research approach, a purposive sample of health care providers (n = 15) was obtained from smaller towns and rural communities in Indiana, United States. Online individual interviews were used for data collection. Thematic analysis showed several concerns including restricted visitation, communication challenges, "hard to say goodbye over iPad", moral distress among providers, and preference for home hospice services. Findings call for strategies to implement best PC practices and programs to support providers and families in smaller towns and rural communities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 by The Hospice and Palliative Nurses Association. All rights reserved.)

Forest disturbances alter land biophysics. Their impacts on local climate and land surface temperature (LST) cannot be directly measured by comparing pre- and post-disturbance observations of the same site over time (e.g., due to confounding such as background climate fluctuations); a common remedy is to compare spatially-adjacent undisturbed sites instead. This space-for-time substitution ignores the inherent biases in vegetation between two paired sites, interannual variations, and temporal dynamics of forest recovery. Besides, there is a lack of observation-based analyses at fine spatial resolutions capable of capturing spatial heterogeneity of small-scale forest disturbances. To address these limitations, here we report new satellite analyses on local climate impacts of forest loss at 30 m resolution. Our analyses combined multiple long-term satellite products (e.g., albedo and evapotranspiration [ET]) at 700 sites across major climate zones in the conterminous United States, using time-series trend and changepoint detection methods. Our method helped isolate the biophysical changes attributed to disturbances from those attributed to climate backgrounds and natural growth. On average, forest loss increased surface albedo, decreased ET, and reduced leaf area index (LAI). Net annual warming-an increase in LST-was observed after forest loss in the arid/semiarid, northern, tropical, and temperate regions, dominated by the warming from decreased ET and attenuated by the cooling from increased albedo. The magnitude of post-disturbance warming was related to precipitation; climate zones with greater precipitation showed stronger and longer warming. Reduction in leaf or LAI was larger in evergreen than deciduous forests, but the recovery in LAI did not always synchronize with those of albedo and ET. Overall, this study presents new evidence of biophysical effects of forest loss on LST at finer spatial resolutions; our time-series method can be further leveraged to derive local policy-relevant ecosystem climate regulation metrics or support model-based climate-biosphere studies., 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 © 2021 Elsevier B.V. All rights reserved.)

Background: Direct bronchial spread of tuberculosis was extensively described in pre-antibiotic human pathology literature but this description has been overlooked in the post-antibiotic era, in which most pathology data come from animal models that emphasise the granuloma. Modern techniques, such as [ 18 F]2-fluoro-2-deoxy-D-glucose (FDG) PET-CT scans, might provide further insight. Our aim was to understand normal early tuberculosis resolution patterns on pulmonary PET-CT scans in treated patients with tuberculosis who were subsequently cured., Methods: In this observational analysis, we analysed data from PredictTB, an ongoing, prospective, randomised clinical trial that examined sequential baseline and week 4 FDG-PET-CT scans from participants successfully treated (sputum culture negative 18 months after enrolment) for drug-susceptible pulmonary tuberculosis in South Africa and China. Participants who were aged 18-75 years, GeneXpert MTB/RIF positive for tuberculosis and negative for rifampicin resistance, had not yet started tuberculosis treatment, had not been treated for active tuberculosis within the previous 3 years, and met basic safety laboratory criteria were included and participants with diabetes, HIV infection, or with extrapulmonary tuberculosis including pleural tuberculosis were excluded. Scans were assessed by two readers for the location of tuberculosis lesions (eg, cavities and consolidations), bronchial thickening patterns, and changes from baseline to week 4 of treatment., Findings: Among the first 124 participants (enrolled from June 22, 2017, to Sept 27, 2018) who were successfully treated, 161 primarily apical cavitary lesions were identified at baseline. Bronchial thickening and inflammation linking non-cavitary consolidative lesions to cavities were observed in 121 (98%) of 124 participants' baseline PET-CT scans. After 4 weeks of treatment, 21 (17%) of 124 participants had new or expanding lesions linked to cavities via bronchial inflammation that were not present at baseline, particularly participants with two or more cavities at baseline and participants from South Africa., Interpretation: In participants with pulmonary tuberculosis who were subsequently cured, the location of cavitary and non-cavitary lesions at baseline and new lesions at week 4 of treatment suggest a cavitary origin of disease and bronchial spread through the lungs. Bronchial spread from cavities might play a larger role in the spread of pulmonary tuberculosis than has been appreciated. Elucidating cavity lesion dynamics and Mycobacterium tuberculosis viability within cavities might better explain treatment outcomes and why some patients are cured and others relapse., Funding: Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership, China Ministry of Science and Technology, National Natural Science Foundation of China, and National Institutes of Health., Translations: For the Chinese, Afrikaans and Xhosa translations of the abstract see Supplementary Materials section., Competing Interests: RJW is supported by Francis Crick Institute, which receives funding from UK Research and Innovation (FC0010218), Wellcome (FC0010218), and Cancer Research UK (FC0010218). RJW also receives support from Wellcome (104803, 203135), the European and Developing Countries Clinical Trials Partnership (EDCTP; SRIA2015-1065), and US National Institutes of Health (NIH; AI115940). GW receives funding from the South African Research Chair Initiative from the National Research Foundation (86535). STM receives grants from the South African Medical Research Council (grant number CDF1576). KA is employed by the Bill & Melinda Gates Medical Research Institute which is a grantee of the Bill & Melinda Gates Foundation but a separate legal entity. All other authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

The COVID-19 pandemic has profoundly impacted the economy and human lives worldwide, particularly the vulnerable low-income population. We employ a large panel data of 5.6 million daily transactions from 2.6 million debit cards owned by the low-income population in the U.S. to quantify the joint impacts of the state lockdowns and stimulus payments on this population's spending along the inter-temporal, geo-spatial, and cross-categorical dimensions. Leveraging the difference-in-differences analyses at the per card and zip code levels, we uncover three key findings. (1) Inter-temporally, the state lockdowns diminished the daily average spending relative to the same period in 2019 by $3.9 per card and $2,214 per zip code, whereas the stimulus payments elevated the daily average spending by $15.7 per card and $3,307 per zip code. (2) Spatial heterogeneity prevailed: Democratic zip codes displayed much more volatile dynamics, with an initial decline three times that of Republican zip codes, followed by a higher rebound and a net gain after the stimulus payments; also, Southwest exhibited the highest initial decline whereas Southeast had the largest net gain after the stimulus payments. (3) Across 26 categories, the stimulus payments promoted spending in those categories that enhanced public health and charitable donations, reduced food insecurity and digital divide, while having also stimulated non-essential and even undesirable categories, such as liquor and cigar. In addition, spatial association analysis was employed to identify spatial dependency and local hot spots of spending changes at the county level. Overall, these analyses reveal the imperative need for more geo- and category-targeted stimulus programs, as well as more effective and strategic policy communications, to protect and promote the well-being of the low-income population during public health and economic crises., Competing Interests: The authors have declared that no competing interests exist.

Although the lack of information on the costs and pricing of healthcare services prevails throughout the medical industry, empiric observations have demonstrated that pricing information is even more obscured in the sperm cryopreservation market. Thus, the objectives of our study are to assess and compare online price transparency and the price of sperm cryopreservation across various healthcare settings in the United States. This study examined online pricing published by facilities that have an active registration to store spermatozoa with the Food and Drug Administration. Less than one-fifth of registered facilities display any pricing information online. Price transparency also varies among census regions and facility types. Nationally, the median initial bank fee and annual price of storage are $350 and $385 respectively. Although there were no differences in the initial fee by facility type and census region, the annual price of storing spermatozoa is highest in the Northeast, which could be attributed to laboratory techniques, demographic patterns or insurance coverage. Guidelines from professional societies or different legislation and regulatory requirements across different US states can increase price transparency, which can promote consumer decision-making and decrease the barrier for men seeking fertility preservation., (© 2021 Wiley-VCH GmbH.)

Background: The roles of US otolaryngology residents have changed in response to the coronavirus disease 2019 (COVID-19) pandemic. As the pandemic peaked in the United States, we characterized resident activities and concerns., Methods: A cross-sectional study of US otolaryngology residents between April 20, 2020 and May 2, 2020., Results: A total of 219 residents at 65/118 (55%) institutions responded. Thirty (14%) residents had been redeployed. Residents reported greatest concerns regarding education (P < .00001). Assuming adequate protective equipment, 55% desired active participation in high-risk procedures on COVID-19-positive patients. Redeployed residents had greater concern for burnout and reduced in-hospital well-being (P < .05). Resident satisfaction correlated with comfort communicating concerns to their department (odds ratio [OR] = 4.9, 95% confidence interval [CI] 1.4-17.3, P = .01) and inversely correlated with low perceived meaning in work (OR = 3.1, CI 1.1-9.1, P = .03)., Conclusion: Otolaryngology resident concerns have evolved as the pandemic progressed. Residency programs should prioritize resident education, well-being in redeployed residents, and open communication as they transition toward recovery., (© 2020 Wiley Periodicals LLC.)

Infertility is defined as not being able to become pregnant after 12 months or more of unprotected sexual intercourse. Female infertility as a serious health issue can result from ovulation disorders, menstrual cycle problems, structural problems, and environmental factors. Ovulation occurs once a month between the time of menarche and menopause. The release of a mature egg from the ovary is controlled with the hypothalamic-pituitary-ovarian axis. Several hormones such as gonadotropin-releasing hormone (GnRH), FSH (follicle-stimulating hormone), LH (luteinizing hormone), estrogen, and progesterone play fundamental roles in the ovulation process. Both FSH and LH are the main treatment for women with ovulation disorders. Depending on the reasons for infertility, several different types of treatment are available for infertile women. Fertility drugs as an important part of treatment work like the natural hormones to treat infertility. Several fertility drugs can regulate ovulation and the release of an egg from the ovary in women with polycystic ovary syndrome (PCOS) or undergoing in vitro fertilization (IVF) treatment. This mini-review is about the FDA-approved prescription drugs that induce ovulation in women with ovulatory problems., (© 2020 Wiley Periodicals, Inc.)

Objective: The coronavirus 2019 (COVID-19) pandemic has had widespread implications on clinical practice at U.S. hospitals. These changes are particularly relevant to otolaryngology-head and neck surgery (OHNS) residents because reports suggest an increased risk of contracting COVID-19 for otolaryngologists. The objectives of this study were to evaluate OHNS residency program practice changes and characterize resident perceptions during the initial phase of the pandemic., Study Design: A cross-sectional survey of U.S. OHNS residents at 81 programs was conducted between March 23, 2020, and March 29, 2020., Results: Eighty-two residents from 51 institutions (63% of invited programs) responded. At the time of survey, 98% of programs had enacted policy changes to minimize COVID-19 spread. These included filtered respirator use for aerosol-generating procedures even in COVID-19-negative patients (85%), decreased resident staffing of surgeries (70%), and reduced frequency of tracheotomy care (61%). The majority of residents (66%) perceived that residents were at higher risk of contracting COVID-19 compared to attendings. Residents were most concerned about protective equipment shortage (93%) and transmitting COVID-19 to patients (90%). The majority of residents (73%) were satisfied with their department's COVID-19 response. Resident satisfaction correlated with comfort level in discussing concerns with attendings (r = 0.72, P < .00001) and inversely correlated with perceptions of increased risk compared to attendings (r = -0.52, P < .00001)., Conclusion: U.S. OHNS residency programs implemented policy changes quickly in response to the COVID-19 pandemic. Sources of resident anxieties demonstrate the importance of open communication and an integrated team approach to facilitate optimal patient and provider care during this unprecedented crisis., Level of Evidence: 4. Laryngoscope, 130:2550-2557, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Barriers to surgical treatment for sleep apnea remain understudied. In this study, we sought to evaluate whether specific demographic and socioeconomic characteristics are associated with whether or not patients receive surgery for sleep apnea management., Methods: The National Inpatient Sample (NIS) database was analyzed for 2007-2014. Patients aged 18 or older with primary or secondary diagnoses of sleep apnea were selected. Patients were sub-categorized by whether they received related soft-tissue removal or skeletal modifying procedures. Age, race, gender, region, insurance, comorbidities, procedure type, and procedure setting were analyzed between surgical and nonsurgical groups., Results: A total of 449,705 patients with a primary or secondary diagnosis of sleep apnea were identified, with 27,841 (5.8%) receiving surgical intervention. Compared with the non-surgical group, patients in the surgical cohort were more likely to be younger, male (74.4% vs. 59.0%), Hispanic (10.2% vs. 6.2%), Asian (3.6% vs. 1.0%) (p < 0.001), and have less clinical comorbidities. Those receiving surgery were more likely to be in the highest income bracket (36.1% versus 25.1%) and utilize private insurance (76.3% vs. 50.8%). Soft-tissue surgeries comprised 88.5% of total procedures while skeletal modifying procedures constituted 11.5% (p < 0.001)., Conclusions: This study identified multiple demographic, socioeconomic, and clinical discrepancies in the utilization of surgical versus nonsurgical management of sleep apnea in the United States. Future studies should examine the causes for these health disparities in the ultimate effort to provide more equitable healthcare in the United States., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To study social and demographic differentiation of assisted reproduction technology (ART) use at the population level in the United States., Design: Population-based study., Setting: Not applicable., Patient(s): Women 15-49 years old in the American Community Survey and National Vital Statistics Birth Certificate data from 2010-2017., Interventions: Not applicable., Main Outcome Measure(s): Birth rate after ART by major sociodemographic categories and likelihood of having an ART birth., Result(s): Net of education, age, period, and marital status, the incidence rates of ART births are lower for black women (0.57 times; 95% CI, 0.52-0.62) and Hispanic women (0.67 times; 95% CI, 0.57-0.62) relative to white women's rates; for Asian women, the incidence rates are 1.21 times that of white women's rates. Further, the incidence rates of ART births are higher for women with more than a 4-year degree (2.08 times; 95% CI, 1.90-2.27) relative to women with a 4-year degree, and are lower for women with less education. Women who are married have an incidence rate of ART that is 5.72 times (95% CI, 5.37-6.09) that of unmarried women. The incidence rates for 2013-2016 are statistically significantly higher than for 2010 by a factor of 1.16 (95% CI, 1.02-1.31), 1.16 (95% CI, 1.03-1.31), 1.27 (95% CI, 1.12-1.43), and 1.51 (95% CI, 1.43-1.82), respectively. The educational differences in ART exist across all age groups from 20 to 49, but are the largest among the 35-39 and 40-44 age groups., Conclusion(s): Large differences in the risk of an ART birth and the proportion of births and the total fertility rate due to ART exist across period, age, race, education, and marital status groups in the United States. Current measures of ART births may disguise an unmet need for ART., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Continuous electronic fetal monitoring (CEFM) is a standard of hospital care during the intrapartum period. We investigated its use on childbirth outcomes in low-risk pregnancies, and examined whether outcomes differed by gestational age within a term pregnancy., Methods: A retrospective secondary data analysis using birth registry data from two diverse northeastern US states from 1992 to 2014. Chi-square test and the Fisher exact tests were used to examine associations between CEFM and childbirth outcomes. Multivariable Poisson regression models were used to estimate risk ratios of childbirth outcomes related to CEFM use, adjusting for potential confounders., Results: Use of CEFM was independently associated with a 10% (State 1) and 40% (State 2) increased risk for primary cesarean delivery and an increased risk for assisted vaginal births (14% and 24%, respectively) after adjustment for confounders. CEFM use was not associated with reduced risk for infant mortality (neonatal mortality, 0-27 days, and post-neonatal mortality, 28-364 days) in term births (37-41 weeks' gestation). After stratifying term pregnancies into early term, full term, and late term, use of CEFM was associated with reduced risk for neonatal mortality in early-term births (37 0/7 weeks' to 38 6/7 weeks' gestation) in State 2 (RR 0.44 [95% CI 0.21-0.92]), but not in State 1. There was no association between CEFM use and infant mortality (neonatal and post-neonatal) in full-term or late-term births., Conclusions: The study results do not support universal use of CEFM in pregnancies that are low-risk and at term., (© 2019 Wiley Periodicals, Inc.)

In 2012, a new influenza vaccine - FLU4 was first licensed in the US. FLU4 is a quadrivalent flu vaccine, which can protect against four flu viruses. Compared to FLU and FLU3, FLU4 gives broader protection against the flu viruses. To our knowledge, few studies have focused on the FLU4 vaccine and its adverse events. Since safety signal detection is important in vaccination, it is necessary to launch such studies on FLU4. In this paper, we used the Vaccine Adverse Event Reporting System (VAERS), which is a national post-marketing vaccine safety surveillance program to identify rare adverse events with year-varying reporting rates for FLU4. The differences in the reporting rates over years are potential signals of vaccine safety issues caused by updates of FLU4 ingredients. We used a likelihood ratio test to simultaneously test the sparsity of events and the differences of event rates over years. We identified 4 adverse events that are rare and have significantly different reporting rates over years.

The awareness of occupational health risk management in the electronics industry is weak in China, and many Chinese occupational health management regulations have not been effectively implemented. China's current occupational hazards classification method and the Environmental Protection Agency (EPA) inhalation risk assessment model recognized internationally were used to perform health risk assessments for a chip manufacturing company in the electronics industry in order to determine the existing problems and put forward the optimization proposals of the occupational hazards classification method in China. The results showed that the detected concentrations of toxic and harmful chemicals in all testing points did not exceed the occupational health exposure limits in China. According to the EPA inhalation risk assessment model, the highest values of non-carcinogenic risks of ammonia, chlorine, fluoride, sulfuric acid, hydrogen chloride, ethylene glycol, phosphine, boron trifluoride, isopropanol, benzene, and xylene were 5.10, 67.12, 1.71, 45.98, 1.83, 1.43, 160.35, 46.56, 2.52, 5.55, and 5.37, respectively, which means workers in electronic chip manufacturing companies exposed to these chemicals have higher occupational health risks. However, on the basis of the occupational hazards classification method, the occupational health risks of exposure to the toxic and hazardous chemicals are relatively harmless operations. The evaluation results of the EPA inhalation risk assessment model are generally higher than those of the occupational hazards classification method. It's recommended to refine the value of occupational exposure limit B, taking more characteristics of the hazard factors into account and fuzzifying the parameters to optimize the occupational hazards classification method. At the same time, it is suggested that the electronic chip manufacturing company should conduct anti-virus risk management covering in three aspects: increasing the awareness of occupational hazards, enhancing system ventilation, and improving personal health management measures.

Promotion of physical activity has been a public health priority for decades. Over two million home healthcare nurses are at the front line to deliver effective health education and health promotion interventions in the United States. The purpose of this systematic review is to examine the effectiveness of nurse-delivered lifestyle physical interventions on physical activity outcomes conducted in home settings. Computerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015. A total of eight quantitative studies were reviewed. Four of the eight studies were randomized control trials and four studies used an uncontrolled pretest-posttest design. The eight studies represented a total of 1,221 participants with mean ages from 43 to 81. Study sample sizes ranged from 16 to 504. Seven of the eight studies demonstrated modest effect of nurse-delivered home-based interventions on physical activity behaviors. Home-based physical activity promotion was most often incorporated into secondary prevention of postacute diseases, chronic disease management, or disease prevention/health promotion. Findings indicate that nurse-delivered home-based physical activity promotion show overall effectiveness in general adult populations. Possible effective intervention domains were also discussed in this review to guide future home-based health promotion. More large randomized controlled trials with longer study/follow-up periods and studies with cost-effectiveness data are warranted in future research.

Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort., Methods: This was a prospective study in which 127 children (age range 8-17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit., Results: The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p = 0.02) and PedsQL social functioning (p < 0.01)., Conclusion: The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument.

Objectives: To compare the effectiveness of chemotherapy in prolonging survival according to age in breast and colon cancer., Design: Retrospective cohort study with a matched cohort analysis based on the conditional probability of receiving chemotherapy., Setting: The 16 Surveillance, Epidemiology, and End Results (SEER) areas from the SEER-Medicare linked database., Participants: Women diagnosed with Stage I to IIIa hormone receptor-negative breast cancer (n = 14,440) and 26,893 men and women with Stage III colon cancer (n = 26,893) aged 65 and older in 1992 to 2009., Measurements: The main exposure was the receipt of chemotherapy, and the main outcome was mortality., Results: In women with breast cancer aged 65 to 69, the risk of all-cause mortality was statistically significantly lower in those who received chemotherapy than in those who did not in the entire cohort (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.57-0.88) and in a propensity-matched cohort (HR = 0.82, 95% CI = 0.70-0.96) after adjusting for measured confounders. These patterns were similar in participants aged 70 to 74 and 75 to 79, but in women aged 80 to 84 and 85 to 89, risk of all-cause mortality was no longer significantly lower in those receiving chemotherapy in the entire and matched cohorts, except that, in a small number of women who received doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), risk of mortality was significantly lower for those aged 80 to 84. Chemotherapy appeared to be effective in all ages from 65 through 84 in participants with Stage III colon cancer. For example, in those aged 85 to 89, chemotherapy was significantly associated with lower risk of mortality in the entire cohort (HR = 0.79, 95% CI = 0.67-0.92) and the matched cohort (HR = 0.79, 95% CI = 0.66-0.95)., Conclusion: The effectiveness of chemotherapy decreased with age in participants with breast cancer, in whom chemotherapy appears to be effective until age 79 except for the doxorubicin-cyclophosphamide combination, which was effective in participants aged 80 to 84. In individuals with Stage III colon cancer, chemotherapy appears to be effective to age 89. These findings were consistent with those of randomized clinical trials., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objective: Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication., Methods: Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest., Results: MMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses., Conclusion: Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication., (Copyright © 2015 by the American College of Rheumatology.)

Background: Breast cancer is the most common female malignant disease, and the second leading cause of cancer-related death in the United States. Acquired resistance to chemotherapeutic drugs is a pivotal reason that leads to worse treatment outcome of breast cancer. Therefore, it is urgent to elucidate the mechanism of drug resistance in breast cancer., Methods: To investigate the underlying molecular basis of the acquired resistant cells to paclitaxel in breast cancer, we used multiple methods including real-time RT-PCR, western blotting analysis, migration and invasion assays, wound healing assay, and transfection., Results: We found that epithelial-mesenchymal transition (EMT) is involved in paclitaxel-resistant (PR) breast cancer cells. The resistant cells with EMT features exhibit increased migration and invasion activities. Mechanistically, high expression of Skp2 was found to be associated with EMT in PR cells. Notably, depletion of Skp2 in PR cells led to partial reversal of EMT phenotype., Conclusions: These findings suggest that Skp2 was critically involved in PR-mediated EMT. Skp2 could be a potential therapeutic target for breast cancer.

Aim: To provide a profile of second malignant neoplasms (SMN) in patients with childhood primary malignant brain tumour originating from neuroepithelial tissues with latest data in a population-based study., Methods: Surveillance, Epidemiology, and End Results (SEER) database (1973-2007) was used to identify above-stated patients. SMN patients were further identified, and standardised incidence ratios (SIRs) and excess absolute risks (EARs) for risk-factor-decided subgroups were calculated. Univariate and multivariate analyses of the association between cumulative incidence of SMN and the risk factors were performed in the whole population., Results: A total of 106 patients were identified as having SMNs. EARs peaked at age at primary diagnosis of 10-14. Males had higher SIRs and EARs than females. Both SIRs and EARs increased after 1990. Age was statistically significant in both univariable and multivariable analyses for cumulative incidence of SMN and RT was not significant in both the analyses, in the whole population of 9075 patients. After follow-up recalculation, matched patients in the ≥1990 group had slightly shorter median interval between primary and secondary cancer than those in the <1990 group, but with no significance., Conclusion: The risk of SMN in children with primary malignant brain tumours in a more advanced treatment era might have changed. During making further advances in the treatment of these neoplasms, minimising toxicities while maintaining promising prognostic outcomes will keep being our goal., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: cancer diagnosis has the potential to overshadow patients' general medical care needs. This study examined changes in general medical care among elderly patients with colorectal cancer (CRC), from before diagnosis through long-term survival., Methods: this longitudinal cohort study used 1993 to 1999 Surveillance, Epidemiology, and End Results and 1991 to 2001 Medicare claims data for 22,161 patients with stage 0 to 3 CRC and 81,669 controls aged 67 to 89 years. Outcomes were preventive services (influenza vaccination, mammography) and, among diabetics, HgbA1c and lipid testing in the phase before diagnosis, the phase after initial treatment, the surveillance phase, and the survival care phase. Logistic regression provided adjusted relative risks of care receipt for patients with stage 0 to 1 cancer, stage 2 to 3 cancer, and no cancer., Results: in the phase before diagnosis through the surveillance phase, patients with stage 0 to 1 CRC had the highest annual preventive service rates. Patients with stage 2 to 3 CRC made substantial gains in preventive service use, especially mammography, after diagnosis (influenza vaccination, 46.4% before diagnosis to 50.2% after initial treatment; mammography, 31.4% before diagnosis to 40.2% after initial treatment) but not in diabetes care (eg, HgbA1c, 53.4% before diagnosis to 54.9% after initial treatment)., Conclusions: CRC diagnosis seems to facilitate receipt of preventive services but not diabetes care for elderly, later-stage patients. Additional strategies such as strengthening partnerships between cancer patients, primary care physicians, and cancer care physicians are needed to improve care for a chronic disease like diabetes.

Background: Many clinical and health services research studies are longitudinal, raising questions about how best to use an individual's comorbidity measurements over time to predict survival., Objectives: To evaluate the performance of different approaches to longitudinal comorbidity measurement in predicting survival, and to examine strategies for addressing the inevitable issue of missing data., Research Design: Retrospective cohort study using Cox regression analysis to examine the association between various Romano-Charlson comorbidity measures and survival., Subjects: Fifty thousand cancer-free individuals aged 66 or older enrolled in Medicare between 1991 and 1999 for at least 1 year., Results: The best fitting model combined both time independent baseline comorbidity and the time dependent prior year comorbidity measure. The worst fitting model included baseline comorbidity only. Overall, the models fit best when using the "rolling" comorbidity measures that assumed chronic conditions persisted rather than measures using only prior year's recorded diagnoses., Conclusions: Longitudinal comorbidity is an important predictor of survival, and investigators should make use of individuals' longitudinal comorbidity data in their regression modeling.

Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas., Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation., Methods: Descriptive cross-sectional study using linked Surveillance, Epidemiology, and End Results (SEER) cancer registry and Medicare claims data for 27,143 individuals ages 66 and older diagnosed with stages I through III CRC between 1992 and 1996., Findings: Over 90% of rural CRC patients lived within 30 miles of a surgical hospital offering CRC surgery, but less than 50% of CRC patients living in small and isolated small rural areas had a medical or radiation oncologist within 30 miles. Rural CRC patients who traveled outside their geographic areas for their cancer care often went great distances. The median distance traveled by rural cancer patients who traveled to urban cancer care providers was 47.8 miles or more. A substantial proportion (between 19.4% and 26.0%) of all rural patients bypassed their closest medical and radiation oncology services by at least 30 miles., Conclusions: Rural CRC patients often travel long distances for their CRC care, with potential associated burdens of time, cost, and discomfort. Better understanding of whether this travel investment is paid off in improved quality of care would help rural cancer patients, most of whom are elderly, make informed decisions about how to use their resources during their cancer treatment.

Background: In 1998, Medicare initiated universal coverage for colorectal cancer (CRC) screening via fecal occult blood testing (FOBT) and sigmoidoscopy. In mid-2001, universal coverage was advanced to screening colonoscopy. This study sought to determine whether trends in CRC testing differed among racial/ethnic, age, or gender subgroups of the Medicare population., Methods: In 2006, claims from 1995 to 2003 were analyzed for annual 5% random samples of fee-for-service Medicare enrollees living in Surveillance, Epidemiology, and End Results (SEER) regions to calculate the annual, age-standardized percentages of subjects who received FOBT, sigmoidoscopy, or colonoscopy. Logistic regression then modeled trends in annual test use within racial/ethnic, age, and gender subgroups across three Medicare coverage periods (precoverage [1995-1997]; limited coverage [1998-mid-2001]; and full coverage [mid-2001-2003])., Results: The annual use of FOBT and sigmoidoscopy declined from 1995 to 2003 in all racial/ethnic groups, but the relative decline in sigmoidoscopy use was greater among whites compared to nonwhites. In contrast, colonoscopy use increased substantially in all racial/ethnic groups. However, relative to the precoverage period among whites, the full-coverage period was associated with significantly greater colonoscopy use among whites (OR=2.14; 95% CI=2.09, 2.19) than blacks (OR=1.86; 95% CI=1.75, 1.96); Asian/Pacific Islanders (OR=1.73; 95% CI=1.62, 1.86); or Hispanics (OR=1.65; 95% CI=1.49, 1.81). The use of colonoscopy during the full-coverage period was also differentially greater among enrollees aged <80 years. CRC testing trends were similar among male and female enrollees., Conclusions: Colonoscopy is supplanting sigmoidoscopy as a CRC test among Medicare enrollees, while FOBT use is in decline. The transition from sigmoidoscopy to colonoscopy has occurred more quickly among white than nonwhite Medicare enrollees.

Background: Black-white disparities exist in receipt of recommended medical care, including colorectal cancer treatment. This retrospective cohort study examines the degree to which health systems (e.g., physician, hospital) factors explain black-white disparities in colon cancer care., Methods: Data from the Surveillance, Epidemiology, and End Results program; Medicare claims; the American Medical Association Masterfile; and hospital surveys were linked to examine chemotherapy receipt after stage III colon cancer resection among 5294 elderly (> or = 66 years of age) black and white Medicare-insured patients. Logistic regression analysis was used to identify factors associated with black-white differences in chemotherapy use. All statistical tests were two-sided., Results: Black and white patients were equally likely to consult with a medical oncologist, but among patients who had such a consultation, black patients were less likely than white patients (59.3% versus 70.4%, difference = 10.9%, 95% confidence interval [CI] = 5.1% to 16.4%, P < .001) to receive chemotherapy. This black-white disparity was highest among patients aged 66-70 years (black patients 65.7%, white patients 86.3%, difference = 20.6%, 95% CI = 10.7% to 30.4%, P < .001) and decreased with age. The disparity among patients aged 66-70 years also remained statistically significant in the regression analysis. Overall, patient, physician, hospital, and environmental factors accounted for approximately 50% of the disparity in chemotherapy receipt among patients aged 66-70 years; surgical length of stay and neighborhood socioeconomic status accounted for approximately 27% of the disparity in this age group, and health systems factors accounted for 12%., Conclusions: Black and white Medicare-insured colon cancer patients have an equal opportunity to learn about adjuvant chemotherapy from a medical oncologist but do not receive chemotherapy equally. Little disparity was explained by health systems; more was explained by illness severity, social support, and environment. Further qualitative research is needed to understand the factors that influence the lower receipt of chemotherapy by black patients.

Objective: Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI., Methods and Results: Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm2; P=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (P=0.007)., Conclusions: This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.