Age-related trajectories of the development of social cognition.

Age-related trajectories of intrinsic functional connectivity (iFC), which represent the interconnections between discrete regions of the human brain, for processes related to social cognition (SC) provide evidence for social development through neural imaging and can guide clinical interventions when such development is atypical. However, due to the lack of studies investigating brain development over a wide range of ages, the neural mechanisms of SC remain poorly understood, although considerable behavior-related evidence is available. The present study mapped vortex-wise iFC features between SC networks and the entire cerebral cortex by using common functional networks, creating the corresponding age-related trajectories. Three networks [moral cognition, theory of mind (ToM), and empathy] were selected as representative SC networks. The Enhanced Nathan Kline Institute-Rockland Sample (NKI-RS, N = 316, ages 8-83 years old) was employed delineate iFC characteristics and construct trajectories. The results showed that the SC networks display unique and overlapping iFC profiles. The iFC of the empathy network, an age-sensitive network, with dorsal attention network was found to exhibit a linear increasing pattern, that of the ventral attention network was observed to exhibit a linear decreasing pattern, and that of the somatomotor and dorsal attention networks was noted to exhibit a quadric-concave iFC pattern. Additionally, a sex-specific effect was observed for the empathy network as it exhibits linear and quadric sex-based differences in iFC with the frontoparietal and vision networks, respectively. The iFC of the ToM network with the ventral attention network exhibits a pronounced quadric-convex (inverted U-shape) trajectory. No linear or quadratic trajectories were noted in the iFC of the moral cognition network. These findings indicate that SC networks exhibit iFC with both low-level (somatomotor, vision) and high-level (attention and control) networks along specific developmental trajectories. The age-related trajectories determined in this study advance our understanding of the neural mechanisms of SC, providing valuable references for identification and intervention in cases of development of atypical SC.

When can we start early enteral nutrition safely in patients with shock on vasopressors?

Shock is a common critical illness characterized by microcirculatory disorders and insufficient tissue perfusion. Patients with shock and hemodynamic instability generally require vasopressors to maintain the target mean arterial pressure. Enteral nutrition (EN) is an important therapeutic intervention in critically ill patients and has unique benefits for intestinal recovery. However, the initiation of early EN in patients with shock receiving vasopressors remains controversial. Current guidelines make conservative and vague recommendations regarding early EN support in patients with shock. Increasing studies demonstrates that early EN delivery is safe and feasible in patients with shock receiving vasopressors; however, this evidence is based on observational studies. Changes in gastrointestinal blood flow vary by vasopressor and inotrope and are complex. The risk of gastrointestinal complications, especially the life-threatening complications of non-occlusive mesenteric ischemia and non-occlusive bowel necrosis, cannot be ignored in patients with shock during early EN support. It remains a therapeutic challenge in critical care nutrition therapy to determine the initiation time of EN in patients with shock receiving vasopressors and the safe threshold region for initiating EN with vasopressors. Therefore, the current review aimed to summarize the evidence on the optimal and safe timing of early EN initiation in patients with shock receiving vasopressors to improve clinical practice.

Amide proton transfer weighted and diffusion weighted imaging based radiomics classification algorithm for predicting 1p/19q co-deletion status in low grade gliomas.

BACKGROUND: 1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI. METHODS: This retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant. RESULTS: The radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist. CONCLUSIONS: Our results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG.

Adversities in childhood and young adulthood and incident cardiovascular diseases: a prospective cohort study.

Background: Much remains unknown regarding the associations of adversities in childhood and adulthood with incident cardiovascular diseases (CVD). We aimed to examine the independent and cumulative relations of adversities in childhood and adulthood with incident CVD and whether these associations can be mitigated by adopting a healthy lifestyle later in life. Methods: We included 136,073 men and women [38-72 years at baseline] free of diagnosed CVD at baseline who responded to surveys on adversities in childhood and adulthood in the United Kingdom Biobank prospective cohort. They were recruited between 2006 and 2010 and were followed-up until 28 January 2021. Adversities included physical abuse, emotional abuse, sexual abuse, emotional neglect, and physical neglect. Participants were categorised into four groups according to the exposure periods, which were no adversity, childhood adversity only, adulthood adversity only, and cumulative adversity (both childhood and adulthood). The primary outcomes included incident fatal and non-fatal CVD events. The modifiable lifestyle factors were smoking, physical activity, diet, sleeping, social or leisure activities, and friend or family visits. Findings: We identified 16,415 (10.71/1000 person-year) incident CVD during a median follow-up of 11.8 years. Compared with participants with no adversity, CVD incidence increased by 11% in those with childhood adversity only (adjusted hazard ratio [HR]: 1.11 [95% CI 1.06-1.17], p < 0.001), 4% in those with adulthood adversity only (1.04 [1.00-1.09], p = 0.05), and 21% in those with cumulative adversity (1.21 [1.16-1.26], p < 0.001). Analysis of interactions showed that adulthood adversity amplified the childhood adversity-CVD association (p for interaction = 0.03). Compared with the participants with one or fewer ideal lifestyle factors, those with more than four ideal factors had a 25%-36% lower risk of CVD across the three adversity groups. Interpretation: Our findings suggested that childhood adversities were associated with an increased risk of CVD which can be magnified by adulthood adversities and substantially mitigated by adopting a healthy lifestyle later in life. Funding: The National Natural Science Foundation of China and Guangzhou Foundation for Basic and Applied Basic Research.

How to achieve green development? A study on spatiotemporal differentiation and influence factors of green development efficiency in China.

For a long time, China 's extensive economic development model has produced a large amount of emissions, which has brought indelible damage to the environment. Green development is of vital importance for China to achieve high-quality development, and it is the core of alleviating environmental problems and promoting sustainable development. How to achieve China 's green development requires us to evaluate the level of green development in China 's provinces and analyze the reasons. In this study, an evaluation index system including undesired output of green development efficiency is constructed, and then the Supe-SBM model is used to assess the green development efficiency of 30 Chinese provinces. This paper also discusses the spatial and temporal differences as well as the factors affecting green development efficiency of green development efficiency among provinces. The findings demonstrate: (1) The green development efficiency in the eastern region is the highest, followed by the western region, while the central region has the lowest, but they all show a downward trend. (2) The spatial characteristics of green development efficiency are remarkable, according to the Global Moran's I index. However, the results of local spatial agglomeration demonstrate "small agglomeration and large dispersion," with the majority of provinces exhibiting L-L agglomeration. (3) Technological Progress, Opening Up, Urbanization Level are positively correlated with the green development efficiency. Industrial Structure, Financial Development, Energy Structure and green development efficiency are significantly negatively correlated, while Environmental Regulation shows no significant impact.

Clinical activity and safety of sintilimab, bevacizumab, and TMZ in patients with recurrent glioblastoma.

PURPOSE: There are limited and no standard therapies for recurrent glioblastoma. We herein report the antitumour activity and safety of sintilimab, bevacizumab and temozolomide (TMZ) in recurrent glioblastoma. METHODS: We retrospectively analysed eight patients with recurrent glioblastoma treated with sintilimab (200 mg) every three weeks + bevacizumab (10 mg/kg) every three weeks + TMZ (200 mg/m²orally) (5 days orally every 28 days for a total of four weeks). The primary objective was investigator-assessed median progression-free survival(mPFS). Secondary objectives were to assess the 6-month PFS, objective response rate (ORR) and duration of response (DOR) accroding to RANO criteria. RESULTS: The mPFS time for 8 patients was 3.340 months (95% CI: 2.217-4.463), The longest PFS was close to 9 months. Five patients were assessed to have achieved partial response (PR), with an overall remission rate of 62.5%, Four patients experienced a change in tumour volume at the best response time of greater than 60% shrinkage from baseline, and one patient remained progression free upon review, with a DOR of more than 6.57 months. The 6-month PFS was 25% (95% CI: 5.0-55.0%). Three patients had a treatment-related adverse events, though no grade 4 or 5 adverse events occurred. CONCLUSION: In this small retrospective study, the combination regimen of sintilimab, bevacizumab and TMZ showed promising antitumour activity in treatment of recurrent glioblastoma, with a good objective remission rate.

Why do Chinese Youth Seek Cancer Risk Information Online? Evidence from Four Cities.

This study, inspired by the Risk Information Seeking and Processing (RISP) model, examines the mechanisms by which perceived hazard characteristics and the informational subjective norms of Chinese youth, aged from 14 to 44 years old, become associated with their intentions to seek cancer risk information online. A sample of 684 Chinese youths was collected from four cities in Mainland China with results revealing that perceived hazard characteristics and informational subjective norms motivate their online cancer risk information seeking intentions. Specifically, perceived probability, perceived severity, and institutional trust are positively related to negative affect, however the relationship between personal control and negative affect is not significant. Institutional trust and personal control are positively related to positive affect while perceived probability and perceived severity have no significant effect on positive affect. Negative affect and informational subjective norms are positively related to perceived information insufficiency, while the relationship between positive affect and perceived information insufficiency is not significant. Negative affect, positive affect, informational subjective norms, and perceived information insufficiency are all positively related to the online cancer risk information seeking intentions of Chinese youth.

Automated detection and segmentation of pleural effusion on ultrasound images using an Attention U-net.

BACKGROUND: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E-FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. METHODS: An Attention U-net and a U-net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. RESULTS: In 10 random tests, the Attention U-net and U-net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U-net performed better at identifying negative images than the U-net, which had an average specificity of 91% compared to 86% for the U-net. Additionally, the Attention U-net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U-net's average dice coefficient of 0.82. CONCLUSIONS: The Attention U-net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E-FAST in clinical work.

MEAN ARTERIAL PRESSURE/NOREPINEPHRINE EQUIVALENT DOSE INDEX AS AN EARLY MEASURE FOR MORTALITY RISK IN PATIENTS WITH SHOCK ON VASOPRESSORS.

ABSTRACT: Purpose: We aimed to investigate the association between the early mean arterial pressure (MAP)/norepinephrine equivalent dose (NEQ) index and mortality risk in patients with shock on vasopressors and further identify the breakpoint value of the MAP/NEQ index for high mortality risk. Methods: Based on the Medical Information Mart for Intensive Care IV database, we conducted a retrospective cohort study involving 19,539 eligible intensive care unit records assigned to three groups (first tertile, second tertile, and third tertile) by different MAP/NEQ indexes within 24 h of intensive care unit admission. The study outcomes were 7-, 14-, 21-, and 28-day mortality. A Cox model was used to examine the risk of mortality following different MAP/NEQ indexes. The receiving operating characteristic curve was used to evaluate the predictive ability of the MAP/NEQ index. The restricted cubic spline was applied to fit the flexible correlation between the MAP/NEQ index and risk of mortality, and segmented regression was further used to identify the breakpoint value of the MAP/NEQ index for high mortality risk. Results: Multivariate Cox analysis showed that a high MAP/NEQ index was independently associated with decreased mortality risks. The areas under the receiving operating characteristic curve of the MAP/NEQ index for different mortality outcomes were nearly 0.7. The MAP/NEQ index showed an L-shaped association with mortality outcomes or mortality risks. Exploration of the breakpoint value of the MAP/NEQ index suggested that a MAP/NEQ index less than 183 might be associated with a significantly increased mortality risk. Conclusions: An early low MAP/NEQ index was indicative of poor prognosis in patients with shock on vasopressors.

Ultrasonographic Assessment of Gastric Volume in Fasted Patients Undergoing Gastrointestinal Endoscopy Under Sedation.

Purpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines. Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated. Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76-0.82; P<0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented. Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.

The effects of early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.

Background: The effects of early mobilization (EM) on intensive care unit (ICU) patients remain unclear. A meta-analysis of randomized controlled trials was performed to evaluate its effect in mechanically ventilated adult ICU patients. Methods: We searched randomized controlled trials (RCTs) published in Medline, Embase, and CENTRAL databases (from inception to November 2022). According to the difference in timing and type, the intervention group was defined as a systematic EM group, and comparator groups were divided into the late mobilization group and the standard EM group. The primary outcome was mortality. The secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV), and adverse events. EM had no impact on 180-day mortality and hospital mortality between intervention groups and comparator groups (RR 1.09, 95% CI 0.89-1.33, p = 0.39). Systemic EM reduced the ICU length of stay (LOS) (MD -2.18, 95% CI -4.22--0.13, p = 0.04) and the duration of MV (MD -2.27, 95% CI -3.99--0.56, p = 0.009), but it may increase the incidence of adverse events in patients compared with the standard EM group (RR 1.99, 95% CI 1.25-3.16, p = 0.004). Conclusion: Systematic EM has no significant effect on short- or long-term mortality in mechanically ventilated adult ICU patients, but systematic EM could reduce the ICU LOS and duration of MV.

Synchronous multimode ultrasound for assessing right-to-left shunt: a prospective clinical study.

Background: Right-to-left shunt (RLS) is associated with several conditions and causes morbidity. In this study, we aimed to evaluate the effectiveness of synchronous multimode ultrasonography in detecting RLS. Methods: We prospectively enrolled 423 patients with high clinical suspicion of RLS and divided them into the contrast transcranial Doppler (cTCD) group and synchronous multimode ultrasound group, in which both cTCD and contrast transthoracic echocardiography (cTTE) were performed during the same process of contrast-enhanced ultrasound imaging. The simultaneous test results were compared with those of cTCD alone. Results: The positive rates of grade II (22.0%:10.0%) and III (12.7%:10.8%) shunts and the total positive rate (82.1748%) in the synchronous multimode ultrasound group were higher than those in the cTCD alone group. Among patients with RLS grade I in the synchronous multimode ultrasound group, 23 had RLS grade I in cTCD but grade 0 in synchronous cTTE, whereas four had grade I in cTCD but grade 0 in synchronous cTTE. Among patients with RLS grade II in the synchronous multimode ultrasound group, 28 had RLS grade I in cTCD but grade II in synchronous cTTE. Among patients with RLS grade III in the synchronous multimode ultrasound group, four had RLS grade I in cTCD but grade III in synchronous cTTE. Synchronous multimode ultrasound had a sensitivity of 87.5% and specificity of 60.6% in the patent foramen ovale (PFO) diagnosis. Binary logistic regression analyses showed that age (odds ratio [OR] = 1.041) and risk of paradoxical embolism score ≥ 7 (OR = 7.798) were risk factors for stroke recurrence, whereas antiplatelets (OR = 0.590) and PFO closure with antiplatelets (OR = 0.109) were protective factors. Conclusion: Synchronous multimodal ultrasound significantly improves the detection rate and test efficiency, quantifies RLS more accurately, and reduces testing risks and medical costs. We conclude that synchronous multimodal ultrasound has significant potential for clinical applications.

Mechanisms of autophagy and endoplasmic reticulum stress in the reversal of platinum resistance of epithelial ovarian cancer cells by naringin.

OBJECTIVE: Our previous studies showed that naringin (Nar) can effectively reverse the cisplatin resistance of ovarian cancer cells. This study aims to explore the potential mechanism by which Nar reverses cisplatin resistance in ovarian cancer. METHODS: The proliferative activity of cells was evaluated using CCK8 and cell clone formation assays. Autophagic flux in cells was evaluated via LC3B immunofluorescence and monodansylcadaverine (MDC) staining. The expression levels of autophagy, endoplasmic reticulum (ER) stress, and apoptosis-related proteins were detected via Western blotting. Autophagy and ER stress were regulated using siATG5, siLC3B, rapamycin (Rap), chloroquine (CQ), 4-phenylbutyric acid (4-PBA), and thapsigargin (TG). siATG5 and siLC3B are short interfering RNAs (siRNAs) used to knock down the expression of ATG5 and LC3B genes, respectively. RESULTS: Nar inhibited autophagy in SKOV3/DDP cells by activating the PI3K/AKT/mTOR pathway. And Nar increased the levels of ER stress-related proteins, namely, P-PERK, GRP78, and CHOP, and promoted apoptosis in SKOV3/DDP cells. Moreover, treatment with the inhibitor of ER stress alleviated apoptosis induced by Nar in SKOV3/DDP cells. In addition, compared to cisplatin or naringin alone, the combination of Nar and cisplatin significantly reduced the proliferative activity of SKOV3/DDP cells. And siATG5, siLC3B, CQ or TG pretreatment further inhibited the proliferative activity of SKOV3/DDP cells. Conversely, Rap or 4-PBA pretreatment alleviated the cell proliferation inhibition caused by Nar combined with cisplatin. CONCLUSION: Nar not only inhibited the autophagy in SKOV3/DDP cells by regulating the PI3K/AKT/mTOR signalling pathway, but also promoted apoptosis in SKOV3/DDP cells by targeting ER stress. Nar can reverse the cisplatin resistance in SKOV3/DDP cells through these two mechanisms.

The Interactive Effect of Stressor Appraisals and Personal Traits on Employees' Procrastination Behavior: The Conservation of Resources Perspective.

Purpose: Procrastination has become a pervasive phenomenon in the workplace, yet knowledge of its antecedents remains limited. Therefore, this study explains when and why employees procrastinate. As procrastination is an individual intentional behavior to escape potential resource loss by taking actions to relax; this study regards procrastination as resource-protection behavior. Building on the conservation of resources (COR) theory, the purpose of the current study is to explore the direct impact of external situational factors (ie, stressor appraisals) and individual traits (ie, personality) and their interactive effect on workplace procrastination behavior. Participants and Methods: The study adopts a quantitative approach and uses two-wave data. Data was collected through the randomized cluster sampling technique and a structured questionnaire survey. The sample consisted of civil servants in an organization located in the Shandong province of China. Received 347 valid questionnaires representing an overall response rate of 87%. The theoretical model was tested through confirmatory factor analysis and regression analyses using Mplus 7.2. Results: The results show that hindrance stressor appraisal is positively related to procrastination, whereas challenge stressor appraisal is negatively related to procrastination. Neuroticism had a positive relationship with procrastination, while conscientiousness had a negative relationship with procrastination. Conscientiousness moderates the relationship between challenge stressor appraisal and procrastination such that the relationship is salient under high conscientiousness. Conclusion: Overall, our study suggests that procrastination is affected by personal traits and workplace stressor appraisals. This study makes potential contributions to employees' procrastination literature by and its understanding within the job procrastination knowledge base. Also, this study confirms the comprehensive reach and applicability of the COR theory developed by scholars such as Hobfoll (1989). In practically, the research benefits organizations by providing suggestions for managing employees' procrastination behavior.

Predicting COVID-19 vaccination intentions: the roles of threat appraisal, coping appraisal, subjective norms, and negative affect.

BACKGROUND: As a new disease, communities possess little natural immunity to COVID-19 and vaccines are considered critical to preventing and reducing the incidence of severe illness. This study, inspired by Protection Motivation Theory (PMT), examines the relationship between citizens' threat appraisal, coping appraisal, subjective norms, negative affect, and their COVID-19 vaccination intentions. METHODS: A sample of 340 citizens from two main cities in Mainland China, Xi'an and Wuxi, was used for data analysis. Structural Equation Modeling (SEM) was employed with latent and observed variables to test hypotheses. Data were analyzed using AMOS 24.0. RESULTS: Several findings extend current understanding. Firstly, our proposed model explains 73% of the variance in vaccination intentions. Secondly, perceived severity only indirectly shapes COVID-19 vaccination intentions through negative affect. Thirdly, negative affect and response costs are negatively related to COVID-19 vaccination intentions. Finally, Perceived probability, subjective norms, response efficacy and self-efficacy are positively related to COVID-19 vaccination intentions; among them, self-efficacy contributes the most, followed by response efficacy and subjective norms, and lastly perceived probability. CONCLUSION: Theoretically, this study increases current understanding about subjective norms and affective responses. We provoke a certain amount of thought about the role of affect response in relation to threat appraisal and vaccination intentions. Specifically, governments must be vigilant that citizens' negative affect, such as fear, may cause vaccine hesitation.

Improving cascade outcomes for active TB: A global systematic review and meta-analysis of TB interventions.

BACKGROUND: To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. METHODS AND FINDINGS: In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). CONCLUSIONS: Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly because of its high rate of metastasis. Thus, elucidation of the molecular mechanisms underlying HCC metastasis is of great significance. Glycosylation is an important post-translational modification that is closely associated with tumor progression. Altered glycosylation including the altered sialylation resulting from aberrant expression of ß-galactoside α2,6 sialyltransferase 1 (ST6GAL1) has long been considered as an important feature of cancer cells. However, there is limited information on the roles of ST6GAL1 and α2,6 sialylation in HCC metastasis. Here, we found that ST6GAL1 and α2,6 sialylation were negatively correlated with the metastatic potentials of HCC cells. Moreover, ST6GAL1 overexpression inhibited migration and invasion of HCC cells in vitro and suppressed HCC metastasis in vivo. Using a metabolic labeling-based glycoproteomic strategy, we identified a list of sialylated proteins that may be regulated by ST6GAL1. In particular, an increase in α2,6 sialylation of melanoma cell adhesion molecule (MCAM) inhibited its interaction with galectin-3 and decreased its expression on cell surface. In vitro and in vivo analysis showed that ST6GAL1 exerted its function in HCC metastasis by regulating MCAM expression. Finally, we found the relative intensity of sialylated MCAM was negatively correlated with tumor malignancy in HCC patients. Taken together, these results demonstrate that ST6GAL1 may be an HCC metastasis suppressor by affecting sialylation of MCAM on cell surface, which provides a novel insight into the roles of ST6GAL1 in HCC progression and supports the functional complexity of ST6GAL1 in a cancer type- and tissue type-specific manner.

Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015.

PURPOSE: Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS: Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS: Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION: Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.