Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner.

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

Prevalence of osteoporosis among patients after stem cell transplantation: a systematic review and meta-analysis.

The prevalence of osteoporosis in post stem cell transplantation (SCT) is poorly defined. We performed a systematic review and meta-analysis to determine the prevalence of osteoporosis in patients with hematologic diseases who underwent SCT. PubMed, EMBASE, and Web of Science were searched (from inception to 30th April 2023) using Medical Subject Headlines to find studies that assessed the prevalence of osteoporosis among post SCT. Thirteen articles meeting the inclusion criteria were included in the analysis. The pooled prevalence rates of osteoporosis, osteopenia, and decreased bone mineral density (BMD) were determined to be 14.2% (95% CI 9.7-18.8), 36.0% (95% CI 23.8-48.2), and 47.8% (95% CI 36.6-58.9), respectively. Substantial heterogeneity was observed among the included studies (I² values ranged from 81% to 99%). Subgroup analyses revealed variations in prevalence based on gender, follow-up duration, age, region, sample size, and study quality. These findings suggest a high prevalence of osteoporosis in post-SCT patients. Given the negative impact of osteoporosis on prognosis and recipient survival, clinicians should prioritize preventive measures, early diagnosis, and effective treatments to minimize its impact.

Risk and Incidence of Cardiovascular Disease Associated with Polycystic Ovary Syndrome.

AIMS: We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD. METHODS: We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. Global incidence of PCOS-associated CVD was calculated by a population attributable fraction (PAF) modelling using the pooled RR, PCOS prevalence, CVD incidence number and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. RESULTS: The risk of CVD was significantly increased in the women with PCOS for all-age group (pooled RR 1.51, 95% CI 1.36-1.69), and 10- to 54-year-old (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS associated CVD cases in women across all-age group has rised from 102 530 to 235 560. The most affected regions were East Asia & Pacific (108 430, 66 090-166 150) in 2019. The South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%; 0.41-0.56) is faster than that of the all-age group (0.34; 0.27-0.42). The middle- or low-middle sociodemographic index countries, experienced higher increase trend of CVD due to PCOS in the past thirty years. CONCLUSIONS: Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with high PCOS-associated CVD burden, especially premature CVD in women under 55 years.

Studies have reported cardiovascular disease (CVD) is the leading cause of mortality for women. Meanwhile, women with polycystic ovary syndrome (PCOS) substantially elevate the risk of CVD. However, no studies have quantified the impact of PCOS on the overall CVD burden. This study performed a meta-analysis to assess the risk of CVD in all-age group and 10 to 54 years old women, living with PCOS with 17 articles, and estimated the burdens of PCOS-associated CVD burden, by global, 7 World-bank defined regions, and 204 countries, from 1990 to 2019, using a PAF modelling. Our study implicated women in all-age group, and 10 to 54 years old with PCOS face a 1.51-fold, and 1.37-fold increased risk of CVD compared those without, respectively. Globally, approximately 0.85% of CVD new cases in 2019 were associated with PCOS, corresponded a more than 2-fold increase of PCOS-associated CVD cases from 1990. However, the burden of PCOS-associated CVD varies widely by region; for instance, nearly 1.49% of CVD new cases were attributed to PCOS in North America. Meanwhile, the East Asia & Pacific region had the highest PCOS-associated new CVD case, and the South Asia experienced the highest increase in age-standardised incidence rates of CVD due to PCOS. Notably, we found higher worldwide PAFs, and annual increase ASIR than that in all-age group women. This result suggests that premature CVD in women with PCOS under 55 years deserve more attention.

Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study.

Background: Human immunodeficiency virus (HIV) significantly increases the risk of non-Hodgkin lymphoma (NHL) development, yet the population-level impact on NHL burden is unquantified. We aim to quantify this association and estimate the global burden of HIV-associated NHL. Methods: In this meta-analysis, we searched five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) from database inception up to September 13, 2023, identifying cohort, case-control, or cross-sectional studies with an effective control group to assess NHL risk among individuals with HIV infection, with two authors extracting summary data from reports. Global and regional HIV-associated population attributable fraction (PAF) and NHL disease burden were calculated based on the pooled risk ratio (RR). HIV prevalence and NHL incidence were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Trends in NHL incidence due to HIV were assessed using age-standardised incidence rate (ASIR) and estimated annual percentage change (EAPC). This study was registered with PROSPERO (CRD42023404150). Findings: Out of 14,929 literature sources, 39 articles met our inclusion criteria. The risk of NHL was significantly increased in the population living with HIV (pooled RR 23.51, 95% CI 17.62-31.37; I2 = 100%, p < 0.0001), without publication bias. Globally, 6.92% (95% CI 2.18%-11.57%) of NHL new cases in 2019 were attributable to HIV infection (30,503, 95% CI 9585-52,209), which marked a more than three-fold increase from 1990 (8340, 95% CI 3346-13,799). The UNAIDS region of Eastern and Southern Africa was the highest affected region, with 44.46% (95% CI 19.62%-58.57%) of NHL new cases attributed to HIV infection. The Eastern Europe and Central Asia region experienced the highest increase in ASIR of NHL due to HIV in the past thirty years, wherein the EAPC was 8.74% (95% CI 7.66%-9.84%), from 2010 to 2019. Interpretation: People with HIV infection face a significantly increased risk of NHL. Targeted prevention and control policies are especially crucial for countries in Eastern and Southern Africa, Eastern Europe and Central Asia, to achieve the UNAIDS's '90-90-90' Fast-Track targets. Limited studies across diverse regions and heterogeneity between research have hindered precise estimations for specific periods and regions. Funding: Sichuan Provincial People's Hospital, Chengdu, China; Health Care for Cadres of Sichuan Province, Chengdu, China; Science and Technology Department of Sichuan Province, Chengdu, China.

Relationship between immune nutrition index and all-cause and cause-specific mortality in U.S. adults with chronic kidney disease.

Objective: The available evidence regarding the association of immune nutrition status with chronic kidney disease (CKD) is limited. Thus, the present study examined whether immunonutrition indices were associated with renal function and mortality among CKD individuals. Research design and methods: This study enrolled 6,099 U.S. adults with CKD from the NHANES 2005-2018 database. Participants were matched with National Death Index records until 31 December 2019 to determine mortality outcomes. The time-dependent receiver operating characteristic was utilized to identify the most effective index among the prognostic nutritional index (PNI), system inflammation score (SIS), Naples prognostic score (NPS), and controlling nutritional status (CONUT) for predicting mortality. Cox regression models were employed to evaluate the associations of immunonutrition indices with mortality in participants with CKD. Results: The PNI exhibited the strongest predictive power among the four indices evaluated and the restricted cubic spline analysis revealed a cutoff value of 51 for the PNI in predicting mortality. During a median follow-up of 72 months (39-115 months), a total of 1,762 (weighted 24.26%) CKD participants died from all causes. The Kaplan-Meier curve demonstrated a reduced risk of death for the subjects with a higher PNI compared to those in the lower group. Besides, after adjusting for multiple potential confounders, a higher PNI remained an independent predictor for lower risks of all-cause mortality (HR 0.80, 95%CI: 0.71-0.91, p < 0.001) and cardiovascular disease (CVD) mortality (HR 0.69, 95%CI: 0.55-0.88, p = 0.002) in individuals with CKD. Conclusion: In CKD, a higher PNI level was significantly associated with lower mortality from all causes and CVD. Thus, the clinical utility of this immunonutrition indicator may facilitate risk stratification and prevent premature death among patients with CKD.

RDW-SD and PCT Are Potential Prognostic Factors for In-hospital Death in Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

PURPOSE: Our study aimed to explore potential prognostic factors in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients from easily accessible laboratory data and to investigate whether the combination of these indicators with a score for toxic epidermal necrolysis (SCORTEN) can improve the predictive value. METHODS: Data from 85 SJS/TEN patients hospitalized from 2010 to 2021 were retrospectively analyzed. The primary outcome was in-hospital mortality. Univariate analysis was used to screen for laboratory indexes associated with death. Logistic regression was used to analyze significant risk factors for death. The differentiation and calibration of SCORTEN and modified score were assessed using receiver operating characteristic (ROC) curves and Hosmer-Lemeshow goodness-of-fit test. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate the incremental prognostic value. RESULTS: Among the 85 patients (37 males, 48 females) aged 14-88 years, the mortality rate was 11.8% (n = 10). SCORTEN had good discrimination and calibration to predict mortality in this cohort of patients (area under the ROC curve [AUC] of 0.874, 95% confidence interval [CI], 0.758-0.990; Hosmer-Lemeshow goodness-of-fit test P = 0.994). Red cell distribution width-standard deviation index (RDW-SD) > 47.9 fL and procalcitonin (PCT) > 0.67 ng/mL were significant risk factors for death. When adding the 2 factors to SCORTEN, AUC was 0.915 (95% CI, 0.833-0.997), but not statistically different compared to SCORTEN alone (P = 0.091). The NRI was 1.2 (95% CI, 0.672-1.728; P < 0.001) and the IDI was 0.09 (95% CI, 0.011-0.173; P = 0.026), still suggesting that the modified score had better discriminatory and predictive power than SCORTEN alone. The modified score also showed good calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.915). CONCLUSIONS: SCORTEN is a good predictor of mortality in SJS/TEN patients in southwest China. Combining RDW-SD > 47.9 fL and PCT > 0.67 ng/mL with SCORTEN may enhance the ability to predict prognosis.

Gut-licensed ß7+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma.

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.

Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women. METHODS: Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed. RESULTS: Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria. CONCLUSIONS: Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk. TRIAL REGISTRATION: PROSPERO registration: CRD42021285206, May 22, 2023.

Thyroid-Related Hormones Changes Predict Changes in Anthropometric Measures and Incidence of Obesity in Chinese Euthyroid Persons.

The purpose of this study was to investigate the correlation of thyroid-related hormones changes within the reference range with the changes in anthropometric measures and incidence of obesity. The study included 4850 subjects with normal thyroid-related hormones at baseline and at follow-up. We evaluated the relationship of changes in thyroid-related biomarkers with anthropometric measures changes and incidence of obesity. In euthyroid persons, changes in serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) concentrations and FT3/FT4 ratio were independent predictors of changes in body mass index (BMI) and waist circumference (WC) in men, changes in serum FT3 and FT4 concentrations and FT3/FT4 ratio were independent predictors of changes in BMI and WC in women. Every single unit increment in ΔFT3/FT4 was accompanied by a 7.144 and 7.572 times risk of having obesity in men and women, respectively. Every single unit decrement in ΔFT4 was accompanied by a 21.0% and 26.9% lower risk of having obesity in men and women, respectively. In conclusion, in euthyroid individuals, changes in thyroid-related hormones were associated with anthropometric measures changes and incidence of obesity.

Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials.

Introduction: Semaglutide shows significant performance on weight reduction in several clinical trials. However, it is not clear what kind of administration frequency or dosage will achieve better effects. This study aims to explore the different therapeutic effect of semaglutide on weight control under the diverse administration circumstances. Methods: The PubMed, Embase, Web of Science, Cochrane Library, and the Clinical Trials.gov were searched from inception until 6 June, 2022 to include randomized controlled trials evaluating the Efficacy and safety of subcutaneous semaglutide in overweight or obese adults. Random effects or fixed effects model was conducted based on the heterogeneity among trials. Subgroup analysis was performed to identify the detailed effects under different intervention situations. Results and discussion: Our study included 13 RCTs involving 5,838 participants with 3,794 ones in semaglutide group and 2,044 in placebo group. Semaglutide was associated with a significant reduction on weight loss related outcomes, including the absolute value of weight loss (WMD -8·97, 95% CI -10·73 to -7·21), percentage of weight loss (WMD -10·00, 95% CI -11·99 to -8·00), body mass index (WMD-3·19, 95% CI -4·02 to -2·37) and waist circumference (WMD -7·21,95% CI -8·87 to -5·56). Subgroup analyses illustrated participants with high weekly dosage, long-term treatment duration and severe baseline BMI (Class II obesity) had a more remarkably decreasing on the main outcomes of weight loss (P for interaction<0·05). Total adverse reactions occurred more frequently in the daily administration group than that in the weekly group (P for interaction =0·01). During the treatment, the incidence rate of hypoglycemia was higher in the group without lifestyle intervention compared with that with lifestyle intervention (P for interaction =0·04). Interpretation Subcutaneous semaglutide had significant benefits on weight loss with reasonable safety in overweight or obese adults. Moreover, additional benefits on cardiometabolic profiles were also seen. We recommended semaglutide treatment to be coupled with lifestyle interventions, and target dose of 2·0 mg or more subcutaneously once weekly. Clinicians can choose suitable treatment schemes based on diverse individual situations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337099, identifier PROSPERO (CRD42022337099).

Association between Helicobacter pylori infection and metabolic syndrome and its components.

Background and aim: The association between Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) has been studied previously; however, the results remain controversial, which could be partly due to the different criteria used for defining MetS. We adopted five MetS criteria to provide better understanding of the association between H. pylori infection and MetS. Methods: Physical examination data of 100,708 subjects were obtained from January 2014 to December 2018. MetS was defined based on five criteria including: International Diabetes Federation (IDF), The Third Report of the National Cholesterol Education Program Expert Panel, Adult Treatment Panel III (ATP III), Joint Statement of International Multi-Societies (JIS), Chinese Diabetes Society (CDS), and the Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 edition)(CDS DM). Multivariate logistic regression analysis was performed to elucidate the association between H. pylori infection and MetS and its components. Results: The prevalence of MetS defined assessed using IDF, ATP III, JIS, CDS and CDS DM criteria was 15.8%, 19.9%, 23.7%, 8.7% and 15.4%, respectively. In males, the prevalence of MetS assessed using the five criteria in H. pylori-positive group was higher than that in negative-group; however, in females, same results were obtained using the three international criteria. In males, the prevalence of all MetS components was found to be higher in the H. pylori-positive group than those in the negative group; however, in females, only the prevalence of dyslipidemia and waist circumferences exhibited significant differences. Multivariate logistic regression analysis revealed that H. pylori infection in males was positively correlated with MetS. Additionally, H. pylori infection was found to be positively correlated with the waist circumference in the general population, and with hypertension and hyperglycemia in males. Conclusions: H. pylori infection was found to be positively associated with MetS in males in China.

Global and Regional Estimate of HIV-Associated Stroke Burden: A Meta-Analysis and Population Attributable Modeling Study.

BACKGROUND: This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke. METHODS: A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index. RESULTS: Out of 10 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18-1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485-31 196) in 1990 to 60 684 (95% CI, 24 281-101 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates. CONCLUSIONS: HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42022367450.

Time to abandon CAR-T monotherapy for solid tumors.

In recent decades, chimeric antigen receptor T (CAR-T) cell therapy has achieved dramatic success in patients with hematological malignancies. However, CAR-T cell therapy failed to effectively treat solid tumors as a monotherapy. By summarizing the challenges of CAR-T cell monotherapy for solid tumors and analyzing the underlying mechanisms of combinatorial strategies to counteract these hurdles, we found that complementary therapeutics are needed to improve the scant and transient responses of CAR-T cell monotherapy in solid tumors. Further data, especially data from multicenter clinical trials regarding efficacy, toxicity, and predictive biomarkers are required before the CAR-T combination therapy can be translated into clinical settings.

Global and regional estimates of cervical cancer burden associated with human immunodeficiency virus infection from 1990 to 2019.

Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.

Benign-malignant classification of pulmonary nodules by low-dose spiral computerized tomography and clinical data with machine learning in opportunistic screening.

BACKGROUND: Many people were found with pulmonary nodules during physical examinations. It is of great practical significance to discriminate benign and malignant nodules by using data mining technology. METHODS: The subjects' demographic data, baseline examination results, and annual follow-up low-dose spiral computerized tomography (LDCT) results were recorded. The findings from annual physical examinations of positive nodules, including highly suspicious nodules and clinically tentative benign nodules, was analyzed. The extreme gradient boosting (XGBoost) model was constructed and the Grid Search CV method was used to select the super parameters. External unit data were used as an external validation set to evaluate the generalization performance of the model. RESULTS: A total of 135,503 physical examinees were enrolled. Baseline testing found that 27,636 (20.40%) participants had clinically tentative benign nodules and 611 (0.45%) participants had highly suspicious nodules. The proportion of highly suspicious nodules in participants with negative baseline was about 0.12%-0.46%, which was lower than the baseline level except the follow-up of >5 years. In the 27,636 participants with clinically tentative benign nodules, only in the first year of LDCT re-examination was the proportion of highly suspicious nodules (1.40%) significantly greater than that of baseline screening (0.45%) (p < 0.001), and the proportion of highly suspicious nodules was not different between the baseline screening and other follow-up years (p > 0.05). Furthermore, 322 cases with benign nodules and 196 patients with malignant nodules confirmed by surgery and pathology were compared. A model and the top 15 most important clinical variables were determined by XGBoost algorithm. The area under the curve (AUC) of the model was 0.76 [95% CI: 0.67-0.84], and the accuracy was 0.75. The sensitivity and specificity of the model under this threshold were 0.78 and 0.73, respectively. In the validation of model using external data, the AUC was 0.87 and the accuracy was 0.80. The sensitivity and specificity were 0.83 and 0.77, respectively. CONCLUSIONS: It is important that pulmonary nodules could be more accurately identified at the first LDCT examination. A model with 15 variables which are routinely measured in the clinic could be helpful to distinguish benign and malignant nodules. It could help the radiological team issue a more accurate report; and it may guide the clinical team regarding LDCT follow-up.

Effects of two-dimensional cyber incivility on employee well-being from a self-determination perspective.

The research attempts to explore the effects of two-dimensional cyber incivility on employee well-being. Based on self-determination theory and regulatory focus theory, we conducted two studies to examine the mediating role of intrinsic motivation and the moderating role of promotion focus between cyber incivility and emotional exhaustion. The results demonstrated that both active and passive cyber incivility predicted increased emotional exhaustion, with intrinsic motivation serving as a key mediator. There was no consistent conclusion of promotion focus's moderating role. High promotion focus might aggravate the negative effect of passive cyber incivility on intrinsic motivation. The present article provides deeper step towards understanding of cyber incivility, which also helps in the development of intervention strategies to lessen or avoid the negative impact of work-related stressful events on employee well-being.

Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival.

Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/- retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/- mice using atorvastatin reduced the cholesterol level in the retina, thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/- retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Diagnostic serum biomarkers associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune rheumatic disease that mostly affects the axial skeleton. This study aimed to investigate reliable diagnostic serum biomarkers for AS. Serum samples were collected from 20 AS patients and 20 healthy controls (HCs) and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The differential metabolites between the AS patients and HCs were profiled using univariate and multivariate statistical analyses. Pathway analysis and a heat map were also conducted. Random forest (RF) analysis and the least absolute shrinkage and selection operator (LASSO) were used to establish predictive and diagnostic models. After controlling the variable importance in the projection (VIP) value > 1 and false discovery rate (FDR) < 0.05, a total of 61 differential metabolites were identified from 995 metabolites, which exhibited significant differences in the pathway analysis and heat map between the AS patients and HCs. RF as a predictive model also identified differential metabolites with 95% predictive accuracy and a high area under the curve (AUC) of 1. A diagnostic model comprising nine metabolites (cysteinylglycine disulfide, choline, N6, N6, N6-trimethyllysine, histidine, sphingosine, fibrinopeptide A, glycerol 3-phosphate, 1-linoleoyl-GPA (18:2), and fibrinopeptide A (3-16)) was generated using LASSO regression, capable of distinguishing HCs from AS with a high AUC of 1. Our results indicated that the UPLC-MS/MS analysis method is a powerful tool for identifying AS metabolite profiles. We developed a nine-metabolites-based model serving as a diagnostic tool to separate AS patients from HCs, and the identified diagnostic biomarkers appeared to have a diagnostic value for AS.

Cytokines and chemokines involved in HLA-B27-positive ankylosing spondylitis-associated acute anterior uveitis.

Purpose: Acute anterior uveitis (AAU) is the most common extra-articular symptom of ankylosing spondylitis (AS). This study aims to reveal the cytokines and chemokines involved in the immunopathogenesis of human leucocyte antigen (HLA)-B27+ AS-associated AAU. Methods: Twenty-one HLA-B27+ AS-associated AAU patients and 21 healthy controls (HCs) were recruited for this study. Serum cytokine concentrations in all 42 subjects were determined by the Meso Scale Discovery (MSD) electrochemiluminescence method. In each sample, 34 cytokines, 10 chemokines, eight angiogenesis mediators, and four vascular injury mediators were measured. The differences in cytokine and chemokine concentrations were compared between the two groups. Results: Concentrations of serum IL-3, TNF-α, IL-6, IL-17D, IL-22, IP10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13 were significantly higher in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). In contrast, concentrations of serum IL-4, IL-8, MIP-1α/CCL3, Eotaxin-3/CCL26, PlGF, VEGF-C, and VEGF-D were significantly lower in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). Conclusions: Significant differences were detected in the levels of several cytokines and chemokines in the serum of HLA-B27+ AS-associated AAU compared with HCs. Some novel differential cytokines and chemokines that have not been reported in other kinds of uveitis were also identified. These results reveal the underlying pathogenesis of HLA-B27+ AS-associated AAU and could potentially aid in clinical diagnosis.

A correlation-based feature analysis of physical examination indicators can help predict the overall underlying health status using machine learning.

As a systematic investigation of the correlations between physical examination indicators (PEIs) is lacking, most PEIs are currently independently used for disease warning. This results in the general physical examination having limited diagnostic values. Here, we systematically analyzed the correlations in 221 PEIs between healthy and 34 unhealthy statuses in 803,614 individuals in China. Specifically, the study population included 711,928 healthy participants, 51,341 patients with hypertension, 12,878 patients with diabetes, and 34,997 patients with other unhealthy statuses. We found rich relevance between PEIs in the healthy physical status (7662 significant correlations, 31.5%). However, in the disease conditions, the PEI correlations changed. We focused on the difference in PEIs between healthy and 35 unhealthy physical statuses and found 1239 significant PEI differences, suggesting that they could be candidate disease markers. Finally, we established machine learning algorithms to predict health status using 15-16% of the PEIs through feature extraction, reaching a 66-99% accurate prediction, depending on the physical status. This new reference of the PEI correlation provides rich information for chronic disease diagnosis. The developed machine learning algorithms can fundamentally affect the practice of general physical examinations.