Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

Global, regional, and national time trends in incidence for tuberculosis, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. OBJECTIVES: This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. METHODS: The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. RESULTS: Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥-0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from -2.2 % [95 % confidence interval (CI): -2.33, -2.05] in high Socio-demographic Index (SDI) countries to -1.7 % [95 % CI: -1.81, -1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. CONCLUSIONS: While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence.

Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.

Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system. Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted. Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of $30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below $30,300/QALY, TACE-LEN is no longer cost-effective. Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.

A local cost simulation-based algorithm to solve distributed constraint optimization problems.

As an important incomplete algorithm for solving Distributed Constraint Optimization Problems (DCOPs), local search algorithms exhibit the advantages of flexibility, high efficiency and high fault tolerance. However, the significant historical values of agents that affect the local cost and global cost are never taken into in existing incomplete algorithms. In this article, a novel Local Cost Simulation-based Algorithm named LCS is presented to exploit the potential of historical values of agents to further enhance the exploration ability of the local search algorithm. In LCS, the Exponential Weighted Moving Average (EWMA) is introduced to simulate the local cost to generate the selection probability of each value. Moreover, populations are constructed for each agent to increase the times of being selected inferior solutions by population optimization and information exchange between populations. We theoretically analyze the feasibility of EWMA and the availability of solution quality improvement. In addition, based on our extensive empirical evaluations, we experimentally demonstrate that LCS outperforms state-of-the-art DCOP incomplete algorithms.

Implementing comprehensive machine learning models of multispecies toxicity assessment to improve regulation of organic compounds.

Machine learning has made significant progress in assessing the risk associated with hazardous chemicals. However, most models were constructed by randomly selecting one algorithm and one toxicity endpoint towards single species, which may cause biased regulation of chemicals. In the present study, we implemented comprehensive prediction models involving multiple advanced machine learning and end-to-end deep learning to assess the aquatic toxicity of chemicals. The generated optimal models accurately unravel the quantitative structure-toxicity relationships, with the correlation coefficients of all training sets from 0.59 to 0.81 and of the test sets from 0.56 to 0.83. For each chemical, its ecological risk was determined from the toxicity information towards multiple species. The results also revealed the toxicity mechanism of chemicals was species sensitivity, and the high-level organisms were faced with more serious side effects from hazardous substances. The proposed approach was finally applied to screen over 16,000 compounds and identify high-risk chemicals. We believe that the current approach can provide a useful tool for predicting the toxicity of diverse organic chemicals and help regulatory authorities make more reasonable decisions.

Characterising complex health needs and the use of preventive therapies in the older population: a population-based cohort analysis of UK primary care and hospital linked data.

BACKGROUND: While several definitions exist for multimorbidity, frailty or polypharmacy, it is yet unclear to what extent single healthcare markers capture the complexity of health-related needs in older people in the community. We aimed to identify and characterise older people with complex health needs based on healthcare resource use (unplanned hospitalisations or polypharmacy) or frailty using large population-based linked records. METHODS: In this cohort study, data was extracted from UK primary care records (CPRD GOLD), with linked Hospital Episode Statistics inpatient data. People aged > 65 on 1st January 2010, registered in CPRD for ≥ 1 year were included. We identified complex health needs as the top quintile of unplanned hospitalisations, number of prescribed medicines, and electronic frailty index. We characterised all three cohorts, and quantified point-prevalence and incidence rates of preventive medicines use. RESULTS: Overall, 90,597, 110,225 and 116,076 individuals were included in the hospitalisation, frailty, and polypharmacy cohorts respectively; 28,259 (5.9%) were in all three cohorts, while 277,332 (58.3%) were not in any (background population). Frailty and polypharmacy cohorts had the highest bi-directional overlap. Most comorbidities such as diabetes and chronic kidney disease were more common in the frailty and polypharmacy cohorts compared to the hospitalisation cohort. Generally, prevalence of preventive medicines use was highest in the polypharmacy cohort compared to the other two cohorts: For instance, one-year point-prevalence of statins was 64.2% in the polypharmacy cohort vs. 60.5% in the frailty cohort. CONCLUSIONS: Three distinct groups of older people with complex health needs were identified. Compared to the hospitalisation cohort, frailty and polypharmacy cohorts had more comorbidities and higher preventive therapies use. Research is needed into the benefit-risk of different definitions of complex health needs and use of preventive therapies in the older population.

Coupling coordination analysis of low-carbon development, technology innovation, and new urbanization: Data from 30 provinces and cities in China.

Technology innovation capability as an endogenous driving force plays an increasingly important role in the low-carbon transformation of new urbanization. This paper's purpose is to delve into the coupling coordination relationship among the three variables, and promote system's and region's synergy development. Based on the coupling coordination degree model, spatial autocorrelation model and obstacle degree model, this paper investigated the coupling coordination of low-carbon development (LCD) quality, technology innovation (TI) capability and new urbanization (NU) level in China from 2009 to 2019. The results indicate: (1) The coupling coordination degree (CCD) of LCD quality, TI capability and NU level in all regions of the country were fluctuating for a long time, and the regions that reach the coordinated development level showed a slow rising trend with obvious regional differences. (2) Three subsystems' CCD showed significant spatial correlation characteristics, and the degree of spatial agglomeration was constantly increasing. (3) The obstacles affecting the systems' synergy mainly reflected in economic and social indexes. In the end, this paper proposed that policy coordination and linkage should be strengthened, emphasizing the integrated development of the three subsystems. It is necessary to formulate development plans in combination with geographic location and resource endowment to enhance the regional driving effect.

Cost-effectiveness analysis of sintilimab plus chemotherapy for advanced or metastatic esophageal squamous cell carcinoma.

Background: Sintilimab plus chemotherapy (SIDCHM) is more effective than placebo plus chemotherapy (PLCHM) for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, considering the high cost of sintilimab, this study evaluated the cost-effectiveness of SIDCHM in comparison with PLCHM for advanced or metastatic ESCC from the Chinese healthcare system perspective. Methods: Polymorphic Markov models were constructed to simulate the course and cost of SIDCHM. Treatment drug costs were calculated at national list prices and clinical data, other costs, and utility values were extracted from the reference literature. Primary outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the model was verified by one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: SIDCHM obtained 1.03 QALYs at $24,044.49, whereas the effectiveness and cost of PLCHM were 0.67 QALYs and $14,166.24, respectively. The ICER for SIDCHM versus PLCHM was $23,458.08/QALY. The utility of the PFS state was the parameter that had the greatest effect on the ICER. The PSA showed that SIDCHM had an 86% probability of being cost-effective at the willingness-to-pay threshold of 3* Chinese gross domestic product per capita ($37,653/QALY). Conclusion: From the Chinese healthcare system perspective, SIDCHM is considered a cost-effective treatment option compared with PLCHM as first-line therapy for advanced or metastatic ESCC.

Cost-effectiveness analysis of adebrelimab combined with chemotherapy for extensive-stage small cell lung cancer.

Background: The findings of the CAPSTONE-1 trial showed that adebrelimab in combination with chemotherapy (etoposide-carboplatin) (ADCHM) is clinically beneficial as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), compared with placebo plus chemotherapy (PLCHM, etoposide-carboplatin). However, owing to the higher cost of adebrelimab, it is unclear whether ADCHM is cost-effective compared with PLCHM. This study aimed to evaluate the cost-effectiveness of ADCHM as a first-line treatment for patients with ES-SCLC from the perspective of the Chinese healthcare system. Methods: A Markov model with three health states was developed to assess the cost-effectiveness of ADCHM as a first-line treatment option with ES-SCLC. Clinical data were obtained from the CAPSTONE-1 trial. Costs of the drug were calculated at national tender prices, and other costs and utility values were obtained from published literature. The outcomes included life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Results: The ADCHM group achieved 1.21 QALYs (2.47 LYs) for $25,312, whereas the PLCHM group achieved 0.81 QALYs (1.59 LYs) for $14,846. The ICER for ADCHM versus PLCHM was $25914 per QALY gained. The variables with the greatest impact on the model results were the utility value of progressive disease, the utility value of progression-free survival, and the price of adebrelimab (100 mg). At a willingness-to-pay threshold of $37,653/QALY, ADCHM had an 89.1% probability of being cost-effective compared with PLCHM. Conclusion: ADCHM may be a cost-effective first-line treatment strategy for ES-SCLC from the perspective of the Chinese healthcare system.

Prediction Model Risk-of-Bias Assessment Tool for coronary artery lesions in Kawasaki disease.

Objective: To review and critically appraise articles on prediction models for coronary artery lesions (CALs) in Kawasaki disease included in PubMed, Embase, and Web of Science databases from January 1, 1980, to December 23, 2021. Materials and methods: Study screening, data extraction, and quality assessment were performed by two independent reviewers, with a statistics expert resolving discrepancies. Articles that developed or validated a prediction model for CALs in Kawasaki disease were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist was used to extract data from different articles, and Prediction Model Risk-of-Bias Assessment Tool (PROBAST) was used to assess the bias risk in different prediction models. We screened 19 studies from a pool of 881 articles. Results: The studies included 73-5,151 patients. In most studies, univariable logistic regression was used to develop prediction models. In two studies, external data were used to validate the developing model. The most commonly included predictors were C-reactive protein (CRP) level, male sex, and fever duration. All studies had a high bias risk, mostly because of small sample size, improper handling of missing data, and inappropriate descriptions of model performance and the evaluation model. Conclusion: The prediction models were suitable for the subjects included in the studies, but were poorly effective in other populations. The phenomenon may partly be due to the bias risk in prediction models. Future models should address these problems and PROBAST should be used to guide study design.

Technology Acceptance in Socially Assistive Robots: Scoping Review of Models, Measurement, and Influencing Factors.

Objectives: We summarized technology acceptance and the influencing factors of elderly people toward socially assistive robots (SARs). Methods: A scoping review whereby a literature search was conducted in Embase, Cochrane, Scopus, PubMed, and Web of Science databases (2006-2021) to retrieve studies. No restrictions on study methodology were imposed. Results: Out of the 1187 retrieved papers, 35 studies were finally included in the study. The articles covered various aspects, including general attitudes towards using SARs, technology acceptance theory models, and factors associated with technology acceptance. Twelve studies reported a positive attitude towards SARs. Three explicit theoretical frameworks were reported. Studies involving the elderly reported three themes that influence attitudes towards SARs: individual characteristics, concerns/problems regarding robots, and social factors. Conclusions: This review elucidates on the suitability of theory-based framework as applied to acceptance of SARs. We found that research on technology acceptance with regard to SARs is still in the developmental stages, and further studies of assessment tools for SARs are required. It is also essential to consider the factors that influence the acceptance of SARs by older people to ensure that they meet the end goal requirements of the user.

Immune Checkpoint Inhibitors Plus an Anti-VEGF Antibody as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.

Background: Sintilimab + a bevacizumab biosimilar (IBI305) (SB) and atezolizumab + bevacizumab (AB) have been approved for the treatment of unresectable hepatocellular carcinoma (HCC). At present, oncologists and their patients remain indecisive on their preferred treatment regime. Therefore, assessing their efficacy via a network meta-analysis and determining their comparative cost-effectiveness is necessary. Objective: To evaluate the cost-effectiveness of SB and AB compared with sorafenib alone for the treatment of unresectable HCC. Materials and Methods: The data used in our analysis were obtained from patients in ORIENT-32 and IMbrave150 phase III randomized clinical trials. A Bayesian network meta-analysis and cost-effectiveness analysis that included 1,072 patients were performed in this study. A partitioned survival model was applied to the patients with unresectable HCC. The model was designed with a 15-year time horizon, 1-month cycle, and 5% discount rate for costs and outcomes. In China, an incremental cost-effectiveness ratio (ICER) value of less than $33,500 (three times the GDP per capita in 2020) per quality-adjusted life-year (QALY) is considered cost-effective. The influence of parameter uncertainty on the results was verified by one-way deterministic sensitivity analysis and probability sensitivity analysis. Furthermore, scenario analyses of the patient assistance program (PAP) were conducted to explore the cost-effectiveness of SB and AB. Results: For the model of 1,072 patients, treatment with SB produced an additional 0.617 QALYs compared with sorafenib, resulting in an ICER of $39,766.86/QALY. Similarly, treatment with AB produced an additional 0.596 QALYs compared with sorafenib, resulting in an ICER of $103,037.66/QALY. The probability sensitivity analysis showed that when the willingness-to-pay (WTP) threshold was $33,500/QALY, the cost-effectiveness of SB and AB was 15.4 and 0.4%, respectively. However, in the scenario analyses, the probability of SB and AB regimens being cost-effective was 65.4 and 15.8%, respectively, at a WTP of $33,500/QALY. Conclusion: The findings from our study showed that sintilimab + a bevacizumab biosimilar is a cost-effective regimen compared with sorafenib as the first-line therapy for unresectable HCC in China at a $33,500 WTP threshold if sintilimab PAP is considered. However, the atezolizumab + bevacizumab regimen is not cost-effective whether atezolizumab PAP is considered or not.

Strengthening the quality of clinical trials of acupuncture: a guideline protocol.

INTRODUCTION: Acupuncture has been accepted in many Western countries and clinical trials have been increasing recently. However, the problems of insufficient and low-quality evidence remain, and substantially hinder the development of acupuncture clinical trials. We therefore aim to develop a guideline to strengthen the quality of acupuncture clinical trials, in accordance with WHO handbook for guideline development and the Reporting Items for practice Guidelines in HealThcare. The guideline will help to improve the quality of acupuncture clinical trials. METHODS AND ANALYSIS: We will search for studies on the quality of acupuncture clinical trials using PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database, The Cochrane Library, the WHO and Health Technology Assessment websites, and other sources. We will also check reference lists and contact experts in the field. We will systematically evaluate the quality of acupuncture clinical trials, and extract and summarise the quality problems and countermeasures of such trials. We will also systematically review clinical trial quality control manuals and systems and formulate research questions on quality control in acupuncture clinical trials. Finally, we will develop the guideline and establish a comprehensive quality control system to ensure high quality acupuncture clinical trials. We will also evaluate the guideline and will update the guideline to reflect new scientific evidence. ETHICS AND DISSEMINATION: Ethics committee approval and informed consent are not required for developing guideline because only published data will be used, however, we will interview the patients, the ethics committee approval has been got from West China Hospital of Sichuan Unversity (Number: 2021-1188). We will publish all manuscripts arising from this research and present the findings at conferences. GUIDELINE REGISTRATION NUMBER: IPGRP-2021CN093.

A Brief Talk on the Design of Biopharmaceutical Separation and Purification Technology Course.

Biological separation and purification technology is the basic technology of modern biotechnology, which is widely used in the pharmaceutical industry, especially the biopharmaceutical industry. In recent years, the biopharmaceutical industry has had a lot of room for development in the development of science and technology in South Korea, and the research on biopharmaceutical equipment and pharmaceutical technology has also achieved good research results. This article proposes a brief discussion on the design of biopharmaceutical separation and purification technology courses. In this study, by analyzing the synthesis potential of the secondary metabolites of the strain, using the α-glucosidase inhibition rate as an inspection indicator, the fermentation medium of the strain was optimized, and batch fermentation was carried out, and then, the metabolites were separated and purified, and the following conclusion was obtained: the α-glucosidase inhibition rate of the crude extract of the strain in the optimized fermentation medium is 35% higher than that of the initial medium.

Digital financial and banking competition network: Evidence from China.

The rapid development of digital finance resulted in fierce competition in the banking industry. The study used Bank-corporate credit data to measure interbank competition based on social network model, and we transformed the regional digital finance index into bank-level digital finance index using each bank's registry and license information. Furthermore, we employed QAP (quadratic assignment procedure) to empirically test the effects of digital finance on the competitive structure among banks. Based on which, we verified its heterogeneity and investigated the mechanisms through which the digital finance affected the banking competition structure. The study finds that, digital finance reshapes the banking competition structure, and intensifies the inter-bank involution while increasing the evolution. The large nation-owned banks have been in central position in the banking network system, with stronger competitiveness and higher strength of digital finance development. For large banks, digital financial development has no significant impact on inter-bank co-opetition and is only more significantly correlated with banking weighted competitive networks. For small and medium-sized banks, digital finance has a significant impact on both co-opetition and competitive pressure. Meanwhile, digital finance also led to the increasing homogeneous competition. In addition, compared with large nation-owned banks, the competitiveness of small and medium-sized joint-equity commercial banks and urban commercial banks are more vulnerable to digital finance and resulting in homogenization problems. Mechanism analysis showed that (1) digital finance promotes the overall competitiveness of the banking industry by improving the inclusiveness of financial services, which expands the service scope (scale effect); (2) digital finance promotes the competition by improving the pricing ability, risk identification ability and finally the capital allocation ability of banks (Pricing effect). The above findings provide new ideas for the governance of banking competition and the realization of a new pattern of economic development.

Biosafety assessment of Acinetobacter strains isolated from the Three Gorges Reservoir region in nematode Caenorhabditis elegans.

Acinetobacter has been frequently detected in backwater areas of the Three Gorges Reservoir (TGR) region. We here employed Caenorhabditis elegans to perform biosafety assessment of Acinetobacter strains isolated from backwater area in the TGR region. Among 21 isolates and 5 reference strains of Acinetobacter, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii ATCC 19606T, A. junii NH88-14, and A. lwoffii DSM 2403T resulted in significant decrease in locomotion behavior and reduction in lifespan of Caenorhabditis elegans. In nematodes, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii, A. junii and A. lwoffii also resulted in significant reactive oxygen species (ROS) production. Moreover, exposure to Acinetobacter isolates of AC1, AC15, AC18, and AC21 led to significant increase in expressions of both SOD-3::GFP and some antimicrobial genes (lys-1, spp-12, lys-7, dod-6, spp-1, dod-22, lys-8, and/or F55G11.4) in nematodes. The Acinetobacter isolates of AC1, AC15, AC18, and AC21 had different morphological, biochemical, phylogenetical, and virulence gene properties. Our results suggested that exposure risk of some Acinetobacter strains isolated from the TGR region exists for environmental organisms and human health. In addition, C. elegans is useful to assess biosafety of Acinetobacter isolates from the environment.

Socioeconomic Disparities Affect Children's Amygdala-Prefrontal Circuitry via Stress Hormone Response.

BACKGROUND: The socioeconomic status (SES) of a family can affect almost all aspects of a child's life, including health and current and future achievement. The potential adverse effects of low SES on children's emotional development are thought to result from proximal factors such as stress. The underlying neurobiological mechanisms, however, remain elusive. METHODS: The effect of SES on children's integrative cortisol secretion and its modulations on emotion-related brain systems and connectivity were examined in children aged 6 to 12 years. In study 1, we investigated the relationship between SES and cortisol secretion in 239 children. In study 2, using resting-state and task-dependent functional magnetic resonance imaging in a subsample of 50 children, we investigated how SES affects children's amygdala-prefrontal functional organization through cortisol secretion. RESULTS: Children from lower SES exhibited lower cortisol secretion, considering basal cortisol, nocturnal cortisol activity during sleep, and cortisol awakening response, which mediated higher amygdala nuclei intrinsic functional connectivity with the medial and dorsolateral prefrontal cortex (PFC). Critically, these children also exhibited higher task-evoked ventromedial PFC activity through higher intrinsic connectivity of the centromedial amygdala with the medial PFC. They also exhibited higher functional coupling of the centromedial amygdala with the dorsolateral PFC when processing negative emotions. CONCLUSIONS: This study demonstrates that SES shapes children's amygdala-prefrontal circuitry through stress-sensitive cortisol secretion, with the most prominent effect in the centromedial amygdala's functional coordination with the ventromedial and dorsolateral PFC involved in processing negative emotions. Our findings provide important insight into the neurobiological etiology underlying how socioeconomic disparities shape children's emotional development.

Nutritional assessment and risk factors associated to malnutrition in patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors. METHODS: A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status. RESULTS: PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition. CONCLUSION: Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients.

Health care access, health care utilisation and sexual orientation disclosure among Black sexual minority men in the Deep South.

Background Black gay, bisexual, and other sexual minority men (BSMM) account for 39.1% of new HIV infections among men who have sex with men and 78.9% of newly diagnosed cases among Black men. Health care access, health care utilisation and disclosing sexuality to providers are important factors in HIV prevention and treatment. This study explored the associations among sexual orientation disclosure, health care access and health care utilisation among BSMM in the Deep South. METHODS: Secondary analysis of existing data of a population-based study in Jackson, Mississippi, and Atlanta, Georgia, was conducted among 386 BSMM. Poisson regression models were used to estimate prevalence ratios (PR) between sexual orientation disclosure to healthcare providers, health care access and health care utilisation. RESULTS: The mean (±s.d.) age of participants was 30.5 ± 11.2 years; 35.3% were previously diagnosed with HIV and 3.7% were newly diagnosed with HIV. Two-thirds (67.2%) self-identified as homosexual or gay; 70.6% reported being very open about their sexual orientation with their healthcare providers. After adjustment, BSMM who were not open about their sexual orientation had a lower prevalence of visiting a healthcare provider in the previous 12 months than those who were very open with their healthcare provider (PR 0.42; 95% confidence interval 0.18-0.97). CONCLUSION: Clinics, hospitals and other healthcare settings should promote affirming environments that support sexuality disclosure for BSMM.

CRISPR-based assessment of genomic structure in the conserved SQUAMOSA promoter-binding-like gene clusters in rice.

Although SQUAMOSA promoter-binding-like (SPL) transcription factors are important regulators of development in rice (Oryza sativa), prior assessments of the SPL family have been limited to single genes. A functional comparison across the full gene family in standardized genetic backgrounds has not been reported previously. Here, we demonstrate that the SPL gene family in rice is enriched due to the most recent whole genome duplication (WGD). Notably, 10 of 19 rice SPL genes (52%) cluster in four units that have persisted for at least 50 million years. We show that SPL gene grouping and retention following WGD is widespread in angiosperms, suggesting the conservatism and importance of this gene arrangement. We used Cas9 editing to generate transformation lines for all 19 SPL genes in a common set of backgrounds, and found that knockouts of 14 SPL genes exhibited defects in plant height, 10 exhibited defects in panicle size, and nine had altered grain lengths. We observed subfunctionalization of genes in the paleoduplicated pairs, but little evidence of neofunctionalization. Expression of OsSPL3 was negatively correlated with that of its closest neighbor in its synteny group, OsSPL4, and its sister paired gene, OsSPL12, in the opposing group. Nucleotide diversity was lower in eight of the nine singleton genes in domesticated rice, relative to wild rice, whereas the reverse was true for the paired genes. Together, these results provide functional information on eight previously unexamined OsSPL family members and suggest that paleoduplicate pair redundancy benefits plant survival and innovation.