Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Five-year survival prognosis of young, middle-aged, and elderly adult female invasive breast cancer patients by clinical and lifestyle characteristics.

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.

Skin cancer survivorship and sun protection behaviors in the United States.

BACKGROUND: Skin cancer survivors are more vulnerable to subsequent skin cancers and other malignancies, but previous studies have not examined in detail their sun protection behavior prevalence by sociodemographic factors. We aimed to understand the sociodemographic disparities in the prevalence of three important types of sun protection behaviors: using sunscreen, seeking shade, and wearing protective clothing, among skin cancer survivors and those without skin cancer history. METHODS: We used the 2015 U.S. National Health Interview Survey to analyze 29,523 participants, of which 772 were skin cancer survivors and 28,751 were those without skin cancer history. We assessed overall and specific sun protection behavior prevalence based on using sunscreen, seeking shade, and wearing protective clothing. Weighted Poisson regression was used to estimate prevalence ratios. RESULTS: Melanoma and nonmelanoma skin cancer survivors had similar overall sun protection behavior (p > .05). Among all skin cancer survivors, 36.0% infrequently used sunscreen, 50.2% infrequently wore protective clothing, 47.8% infrequently sought shade, and 30.0% lacked frequent overall sun protection, which significantly differed from those without skin cancer history (p < .0001). The prevalence of frequent overall sun protection behavior was lower for those who were younger at survey, males, less educated, single or never married, or lived in poverty, regardless of their skin cancer history (p < .01). CONCLUSIONS: By identifying subpopulations with higher prevalence of infrequent sun protection among those with or without skin cancer history, our findings may encourage efforts to reduce sociodemographic disparities in sun protection behaviors and promote primary and tertiary skin cancer prevention.

Prevalence of Current Cigarette Smoking by Sociodemographic Characteristics in U.S. Cancer Survivors.

BACKGROUND: Cancer survivors are especially vulnerable to the carcinogenic effects of tobacco smoking, but there lacks a study comprehensively examining the sociodemographic disparities in current smoking prevalence in this population. In this study, we quantified the current cigarette smoking prevalence in cancer survivors and those without cancer history by sociodemographic factors, to identify subpopulations with high current smoking burden. METHODS: We conducted a cross-sectional study of 3,679 cancer survivors and 27,350 participants without cancer history who were 18 years of age or above in the 2019 National Health Interview Survey. Data for the study variables were obtained from computer-assisted personal or telephone interviews. Weighted Poisson regression was used to estimate prevalence ratios and 95% confidence intervals. RESULTS: Although the current smoking prevalence for cancer survivors was slightly lower than for those without cancer history, the prevalence exceeded 30% in cancer survivors in poverty or without health insurance. Individuals with significantly higher current smoking prevalence had lower education levels, were unmarried, did not have health insurance, or lived in poverty. The associations of age, sex, race, health insurance status, and poverty status with current smoking significantly differed between cancer survivors and those without cancer history. Sociodemographic disparities in current smoking prevalence were found in survivors of either smoking-related or nonsmoking-related cancers. CONCLUSION: High current smoking prevalence still exists in subpopulations of cancer survivors and those without cancer history. Our findings may strengthen efforts to reduce sociodemographic disparities in current smoking prevalence and to lower the overall smoking prevalence.

Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework.

BACKGROUND: Use of combinations of long-acting ß2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. AIM: The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. METHODS: We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017-2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). RESULTS: Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78-1.01) for the composite events, 0.80 (95% CI, 0.61-1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68-3.25) for unstable angina, 1.00 (95% CI, 0.80-1.24) for congestive heart failure, 0.62 (95% CI, 0.37-1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66-1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. CONCLUSION: Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Associations between sociodemographic factors and breast, cervical, and colorectal cancer screening in the United States.

PURPOSE: Cancer is the second leading cause of death globally and in the U.S., but screening can reduce cancer-related deaths. We analyzed data from a nationwide survey to compare how sociodemographic factors were associated with never or not timely screening for multiple types of cancer, and the use of different colorectal cancer screening procedures. METHODS: We analyzed data from the 2019 U.S. National Health Interview Survey. To understand breast, cervical, and colorectal cancer screening participation among those recommended to screen, we respectively analyzed 8,110 women 45 to 74 years of age, 9,583 women 21 to 65 years of age, and 13,497 individuals 50 to 75 years of age at survey. Weighted Poisson regression was used to estimate the unadjusted and confounding-adjusted prevalence ratio and 95% confidence intervals. RESULTS: In our analysis populations, 6.9% never had a mammogram, 14.6% never screened for cervical cancer, and 26.8% never screened for colorectal cancer; the prevalence respectively increased to 24.7%, 23.8%, and 32.3% for not timely screening according to national guidelines. The prevalence of never screening was 81.9% for non-invasive colorectal cancer tests, compared with 32.5% for colonoscopy or sigmoidoscopy. Individuals with lower education level, with no health insurance, or in poverty had higher prevalence of never screening for all three cancers. There was low sociodemographic disparity for the use of non-invasive colorectal cancer screening tests. CONCLUSION: Socioeconomically disadvantaged individuals have higher prevalence of never or not timely screening. The utilization of non-invasive colorectal cancer screening procedures remains low across sociodemographic groups.

Decentralized H2 Control for Discrete-Time Networked Systems With Positivity Constraint.

In this brief, we study the decentralized H2 state-feedback control problem for networked discrete-time systems with positivity constraint. This problem (for a single positive system), raised recently in the area of positive systems theory, is known to be challenging due to its inherent nonconvexity. In contrast to most works, which only provide sufficient synthesis conditions for a single positive system, we study this problem within a primal-dual scheme, in which necessary and sufficient synthesis conditions are proposed for networked positive systems. Based on the equivalent conditions, we develop a primal-dual iterative algorithm for solution, which helps prevent from converging to a local minimum. In the simulation, two illustrative examples are employed for verification of our proposed results.

Five-year Survival Trends for Young Adult Cancers Diagnosed from 2002 to 2014 in Taiwan and the United States.

BACKGROUND: Young adult cancer incidence has been increasing in Taiwan, but no studies have examined their survival trends. METHODS: We analyzed data from the Taiwan National Health Insurance Research Database and the U.S. Surveillance, Epidemiology, and End Results Program. We obtained the five-year survival estimates and trends for primary invasive cancers diagnosed at 20-39 years of age from 2002 to 2014. When analyzing specific cancers, we focused on the common young adult cancers in Taiwan. For the trend analysis, the average annual percent change (AAPC) was calculated using joinpoint Regression Program. We also obtained estimates stratified by sex or age at cancer diagnosis. RESULTS: The five-year age-standardized relative survival for all young adult cancers combined significantly increased in Taiwan [AAPC = 1.4%; 95% confidence interval (CI), 1.3%-1.5%] and the United States (AAPC = 0.4%; 95% CI, 0.3%-0.6%). Cancers occurring in both sexes had similar trend directions for both sexes. Lung and bronchus cancer, liver cancer, and leukemia had the most survival improvement in both regions. However, the five-year relative survival for cervical cancer declined in Taiwan (AAPC = -0.6%; 95% CI, -1.0% to -0.1%) and did not improve in the United States (AAPC = -0.1%; 95% CI, -0.4%-0.2%). CONCLUSIONS: Survival has improved for most but not all of the common young adult cancer types in Taiwan. Additional studies can understand why survival has not improved for certain cancer types, and examine subtype-specific survival trends. IMPACT: This is the first study of five-year survival trends for young adult cancers in Taiwan and the United States stratified by sex or age at diagnosis.

Significant gaps in hepatitis B vaccination in adults in Viet Nam: Important targets toward hepatitis B elimination by 2030.

BACKGROUND: Gaps in adult hepatitis B vaccination were undefined in Vietnam, a lower-middle-income country. To address these gaps, this study defined hepatitis B vaccine coverage in adults and its associated factors in Ho Chi Minh City (HCMC), Viet Nam. We also proposed interventional strategies, prioritizing gap identification to facilitate hepatitis B elimination by 2030 and beyond. METHOD: During 2019-2020, a multi-stage cluster serosurvey with probability proportional to size was conducted to representatively invite 20,000 adults (18 years or older) throughout HCMC for hepatitis B screening (HBsAg, anti-HBs, and anti-HBc). Serologic results defined two dependent variables: vaccine-induced immunity (i.e., isolated anti-HBs) and susceptibility (i.e., HBV naive). Associations of dependent variables with surveyed demographics, socioeconomic statuses, behaviors, and medical history at risk for hepatitis B were evaluated using weighted Poisson regression. RESULTS: The prevalence was 18.5% (95%CI, 17.3-20.0%) for vaccine-induced immunity and 37.7% (35.6-39.8%) for susceptibility. Even though analyses in the general population revealed a falling trend in vaccine-induced immunity prevalence from younger to older age groups, sensitivity analyses in the non-infected population (i.e., those who were both negative for HBsAg and anti-HBc) showed that younger age groups, especially those aged 30 to 50 years, had the lowest prevalence. Social inequalities existed in different ethnicities, residence areas, education levels, house ownership, and health insurance statuses. There was no significant association between vaccine-induced immunity or susceptibility and risky behaviors and medical histories. CONCLUSION: This study depicts a significant unmet need for hepatitis B vaccination in the general adult population in HCMC, Viet Nam. Indeed, the lack of vaccination was unevenly distributed regarding age groups, geographical areas, and socioeconomic statuses, which reveals profound social disparities. Therefore, to achieve hepatitis B elimination goals, besides the current recommendations for infants and risk-based strategies, hepatitis B vaccination should be recommended for the broader population.

Interrelationships Between Pregnancy Intention, Antenatal Care, and Sociodemographic Factors: Analysis of a Nationwide Population-Based Cross-Sectional Study in Vietnam.

OBJECTIVES: This study aimed to improve the understanding of the interrelationships between sociodemographic factors, pregnancy intention, and antenatal care by: (1) identifying sociodemographic predictors of unintended pregnancy; (2) examining associations between unintended pregnancy types and antenatal care (ANC) inadequacy; (3) examining how the association between unintended pregnancy and ANC inadequacy is modified by maternal characteristics; and (4) identifying sociodemographic predictors of ANC inadequacy by pregnancy intention status. METHODS: We analyzed women 15-49 years of age who participated in the nationwide cross-sectional Vietnam Multiple Indicator Cluster Survey. Pregnancy intention and ANC adequacy were assessed for the most recent live birth within two years preceding survey completion. Weighted Poisson regression was used to estimate risk ratios. RESULTS: Of the 1,474 study participants, 17.8% had unintended pregnancy and 29.0% had inadequate ANC. There was no significant confounding-adjusted association between unintended pregnancy and ANC inadequacy, except in those currently not working. Women with intended pregnancy or unintended pregnancy had significantly higher ANC inadequacy risk if they lived in rural areas, were less educated, and had no media exposure, lower wealth status, or more than two children. Younger age, ever given birth, having child loss, and positive attitude towards partner violence were significant predictors of ANC inadequacy only in women with intended pregnancy. CONCLUSIONS FOR PRACTICE: ANC inadequacy was more strongly predicted by sociodemographic characteristics rather than pregnancy intention, and the sociodemographic variables' prediction of ANC inadequacy was stronger in women with intended pregnancy than unintended pregnancy.

Positive Consensus of Fractional-Order Multiagent Systems Over Directed Graphs.

This article investigates the positive consensus problem of a special kind of interconnected positive systems over directed graphs. They are composed of multiple fractional-order continuous-time positive linear systems. Unlike most existing works in the literature, we study this problem for the first time, in which the communication topology of agents is described by a directed graph containing a spanning tree. This is a more general and new scenario due to the interplay between the eigenvalues of the Laplacian matrix and the controller gains, which renders the positivity analysis fairly challenging. Based on the existing results in spectral graph theory, fractional-order systems (FOSs) theory, and positive systems theory, we derive several necessary and/or sufficient conditions on the positive consensus of fractional-order multiagent systems (PCFMAS). It is shown that the protocol, which is designed for a specific graph, can solve the positive consensus problem of agents over an additional set of directed graphs. Finally, a comprehensive comparison study of different approaches is carried out, which shows that the proposed approaches have advantages over the existing ones.

Effect of empagliflozin versus linagliptin on body composition in Asian patients with type 2 diabetes treated with premixed insulin.

Insulin therapy often increases body weight and leads to visceral fat accumulation. Progression in diabetes is also associated with accelerated loss of muscle mass. Little is known about body composition changes in type 2 diabetes mellitus (T2DM) patients on insulin therapy who use sodium-glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors. This study examined the effect of 25 mg of empagliflozin compared with 5 mg of linagliptin for 24 weeks on body weight and body composition in patients with T2DM on premixed insulin. Body composition was assessed with bioelectrical impedance analysis. The mean difference between the linagliptin and empagliflozin groups in terms of mean body weight change from baseline to 24 weeks was - 1.80 kg (95% CI - 2.57, - 1.03). Empagliflozin also significantly reduced muscle mass (- 1.39 kg, 95% CI - 2.49, - 0.29) and total body water (- 1.07 kg, 95% CI - 1.88, - 0.27) compared with linagliptin. Compared to linagliptin, empagliflozin decreased body fat mass more from baseline to week 24, but this was not significant (- 0.31 kg, 95% CI - 1.51, 0.90). Further research on insulin-treated T2DM patients is necessary to investigate the long-term effects of SGLT2 and DPP4 inhibitors on body composition, as well as their effects on muscle strength and physical function.Trial registration: ClinicalTrials.gov no. NCT03458715, registration date: March 8, 2018.

Young adult cancer incidence trends in Taiwan and the U.S. from 2002 to 2016.

BACKGROUND: Previous studies have not examined young adult cancer incidence trends in Taiwan, or comprehensively compared these trends at two nations with different population genetics, environmental exposures, and health care. Therefore, we compared the incidence rates and trends of the most common young adult cancers diagnosed at 20-39 years of age in Taiwan and the U.S. METHODS: Incidence rates from 2002 to 2016 were calculated from the Taiwan National Health Insurance Research Datasets and the U.S. Surveillance, Epidemiology, and End Results Program. For trend assessment, average annual percent change (AAPC) values were calculated from 15 years of data using Joinpoint Regression Program. We also obtained sex or age of diagnosis stratified estimates. RESULTS: The age-standardized overall young adult cancer incidence rate significantly increased from 2002 to 2016 in both Taiwan (AAPC=1.1%, 95% CI: 0.8-1.5%) and the U.S. (AAPC=1.8%, 95% CI: 1.1-2.4%). Cancers with significantly decreasing trends in Taiwan included cancers of the nasopharynx, liver, and tongue, which were not among the most common young adult cancers in the U.S. Cancers with significantly increasing trends in both Taiwan and the U.S. included colorectal, thyroid, and female breast cancers. Lymphoma, ovarian cancer, and lung and bronchus cancer had significantly increasing trends in Taiwan but not in the U.S. Although cervical cancer had significantly decreasing trends in both nations among those 30-39 years of age, its trend was significantly increasing in Taiwan but decreasing in the U.S. among those 20-29 years of age. CONCLUSION: The types of common young adult cancers as well as their incidence rates and trends differed in Taiwan and the U.S. Future studies should further understand the etiological factors driving these trends.

Further Improvements on Non-Negative Edge Consensus of Networked Systems.

In this article, the non-negative edge consensus problem is addressed for positive networked systems with undirected graphs using state-feedback protocols. In contrast to existing results, the major contributions of this work included: 1) significantly improved criteria of consequentiality and non-negativity, therefore leading to a linear programming approach and 2) necessary and sufficient criteria giving rise to a semidefinite programming approach. Specifically, an improved upper bound is given for the maximum eigenvalue of the Laplacian matrix and the (out-) in-degree of the degree matrix, and an improved consensuability and non-negativevity condition is obtained. The sufficient condition presented only requires the number of edges of a nodal network without the connection topology. Also, with the introduction of slack matrix variables, two equivalent conditions of consensuability and non-negativevity are obtained. In the conditions, the system matrices, controller gain, as well as Lyapunov matrices are separated, which is helpful for parameterization. Based on the results, a semidefinite programming algorithm for the controller is readily developed. Finally, a comprehensive analytical and numerical comparison of three illustrative examples is conducted to show that the proposed results are less conservative than the existing work.

Nonnegative Consensus Tracking of Networked Systems With Convergence Rate Optimization.

This article investigates the nonnegative consensus tracking problem for networked systems with a distributed static output-feedback (SOF) control protocol. The distributed SOF controller design for networked systems presents a more challenging issue compared with the distributed state-feedback controller design. The agents are described by multi-input multi-output (MIMO) positive dynamic systems which may contain uncertain parameters, and the interconnection among the followers is modeled using an undirected connected communication graph. By employing positive systems theory, a series of necessary and sufficient conditions governing the consensus of the nominal, as well as uncertain, networked positive systems, is developed. Semidefinite programming consensus design approaches are proposed for the convergence rate optimization of MIMO agents. In addition, by exploiting the positivity characteristic of the systems, a linear-programming-based design approach is also proposed for the convergence rate optimization of single-input multi-output (SIMO) agents. The proposed approaches and the corresponding theoretical results are validated by case studies.

Consensus of Positive Networked Systems on Directed Graphs.

This article addresses the distributed consensus problem for identical continuous-time positive linear systems with state-feedback control. Existing works of such a problem mainly focus on the case where the networked communication topologies are of either undirected and incomplete graphs or strongly connected directed graphs. On the other hand, in this work, the communication topologies of the networked system are described by directed graphs each containing a spanning tree, which is a more general and new scenario due to the interplay between the eigenvalues of the Laplacian matrix and the controller gains. Specifically, the problem involves complex eigenvalues, the Hurwitzness of complex matrices, and positivity constraints, which make analysis difficult in the Laplacian matrix. First, a necessary and sufficient condition for the consensus analysis of directed networked systems with positivity constraints is given, by using positive systems theory and graph theory. Unlike the general Riccati design methods that involve solving an algebraic Riccati equation (ARE), a condition represented by an algebraic Riccati inequality (ARI) is obtained for the existence of a solution. Subsequently, an equivalent condition, which corresponds to the consensus design condition, is derived, and a semidefinite programming algorithm is developed. It is shown that, when a protocol is solved by the algorithm for the networked system on a specific communication graph, there exists a set of graphs such that the positive consensus problem can be solved as well.

Subsequent primary urogenital cancers among childhood and adolescent cancer survivors in the United States.

PURPOSE: To conduct an updated and comprehensive study on the risks of subsequent primary urogenital cancers for childhood and adolescent cancer survivors. METHODS: This longitudinal study was conducted using 9 cancer registries from the Surveillance, Epidemiology and End Results (SEER) Program with follow-up from 1975 to 2017. There were 43,991 patients diagnosed with first primary cancer from 1975 to 2016 before the age of 20 years who subsequently survived for at least 1 year. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for urogenital cancers were calculated. RESULTS: Compared with the general population, the risk of urinary system cancer was significantly higher in both female (SIR = 5.18, 95% CI: 3.65-7.14) and male (SIR = 2.80, 95% CI: 1.94-3.92) survivors of any first cancer, with shorter median interval length between first cancer and subsequent urinary system cancer for male survivors (19.9 years) than female survivors (29.3 years). Females also had significantly higher SIR than males for subsequent urinary system cancer (SIRfemale:male=1.86, 95% CI: 1.13-3.03) and kidney cancer (SIRfemale:male = 1.97, 95% CI: 1.11-3.53). Compared with the general population, females with any first cancer had significantly higher risks for cancers of the corpus uteri (SIR = 2.32, 95% CI: 1.49-3.45) and vulva (SIR = 4.27, 95% CI: 1.38-9.95). CONCLUSIONS: Childhood and adolescent cancer survivors may have greater female susceptibility for developing subsequent urinary system and kidney cancers, and these survivors may have higher risks for specific types of reproductive system cancers. Our findings may lead to better awareness and surveillance for urogenital cancer by these cancer survivors and their physicians.

Associations between high-sensitivity C-reactive protein and non-communicable diseases in an Asian population: findings from the IFLS study.

Background: There has been no comprehensive study on how high-sensitivity C-reactive protein (hs-CRP) levels, a biomarker of inflammation, are associated with subsequent diagnoses of various non-communicable diseases (NCDs) in Asians. Our study is the first to do so to better compare these associations in an Asian population.Methods: This is a nationwide longitudinal study of 3,410 male and 4,004 female participants of the RAND Indonesian Family Life Survey with a mean age of 42.4 years, to examine associations between increasing hs-CRP levels and risks of heart diseases, stroke, hypertension, diabetes, arthritis, non-cancerous stomach or other digestive diseases, and non-cancerous kidney diseases. We used unadjusted and confounding-adjusted weighted Poisson regression models to respectively examine associations involving hs-CRP as a risk predictor or indicator of chronic inflammation. Several stratified subpopulation analyses were also performed.Results: Increasing hs-CRP levels predicted significantly higher risks of being diagnosed with all of the studied NCDs except stomach or other digestive diseases. After adjusting for confounding, increasing hs-CRP levels were significantly associated with higher risks of diabetes, heart diseases, hypertension, and kidney diseases.Conclusions: Our comprehensive findings on the associations between hs-CRP levels and risks of several NCDs in Asians may have clinical implications and promote additional studies on this topic.

Subsequent Primary Cancers of the Digestive System Among Childhood and Adolescent Cancer Survivors From 1975 to 2015 in the United States.

INTRODUCTION: Among survivors from first primary cancers that occurred during childhood and adolescence, their risks of developing subsequent primary digestive system cancers are not well understood. Therefore, we conducted the largest and most comprehensive analysis examining risks for diverse types of digestive system cancers after survival from a wide variety of first primary childhood and adolescent cancers. METHODS: We identified 41,249 patients diagnosed with first primary cancer from 1975 to 2015 before 20 years of age from 9 Surveillance, Epidemiology and End Results Program registries. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for digestive system cancers were calculated controlling for age, sex, race, and calendar year. RESULTS: Among 41,249 cancer survivors, 133 developed subsequent primary digestive system cancer, with a median digestive system cancer diagnosis age of 37 years. The SIR and AER for any digestive system cancer were highest among survivors of bone cancer, lymphoma, and neuroblastoma. Among survivors from any first primary cancer, the SIR was significantly elevated for cancer of the esophagus, stomach, small intestine, large intestine, liver, and pancreas, whereas the AER was highest for large intestine cancer. DISCUSSION: Childhood and adolescent cancer survivors diagnosed from 1975 to 2015 have significantly elevated risks of digestive system cancers compared with the US general population. Our detailed findings may contribute to surveillance recommendations of childhood and adolescent cancer survivors and promote future studies to further understand mechanisms by which having various first primary cancers lead to subsequent primary digestive system cancers.