Improvement in the 95-95-95 Targets Is Accompanied by a Reduction in Both the Human Immunodeficiency Virus Transmission Rate and Incidence in China.

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Non-invasive assessment of esophageal and fundic varices in patients with primary biliary cholangitis.

OBJECTIVES: The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. METHODS: We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. RESULTS: The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). CONCLUSION: We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. CLINICAL RELEVANCE STATEMENT: The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. KEY POINTS: Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.

Improving glucose oxidase catalysis in Aspergillus niger via Vitreoscilla hemoglobin fusion protein.

Oxygen is crucial for converting glucose to gluconic acid catalyzed by glucose oxidase (Gox). However, industrial gluconic acid production faces oxygen supply limitations. To enhance Gox efficiency, Vitreoscilla hemoglobin (VHb) has been considered as an efficient oxygen transfer carrier. This study identified GoxA, a specific isoform of Gox in the industrial gluconic acid-producing strain of Aspergillus niger. Various forms of VHb expression in A. niger were tested to improve GoxA's catalytic efficiency. Surprisingly, the expression of free VHb, both intracellularly and extracellularly, did not promote gluconic acid production during shake flask fermentation. Then, five fusion proteins were constructed by linking Gox and VHb using various methods. Among these, VHb-GS1-GoxA, where VHb's C-terminus connected to GoxA's N-terminus via the flexible linker GS1, demonstrated a significantly higher Kcat/Km value (96% higher) than GoxA. Unfortunately, the expression of VHb-GS1-GoxA in A. niger was limited, resulting in a low gluconic acid production of 3.0 g/L. To overcome the low expression problem, single- and dual-strain systems were designed with tools of SpyCatcher/SpyTag and SnoopCatcher/SnoopTag. In these systems, Gox and VHb were separately expressed and then self-assembled into complex proteins. Impressively, the single-strain system outperformed the GoxA overexpression strain S1971, resulting in 23% and 9% higher gluconic acid production under 0.6 vvm and 1.2 vvm aeration conditions in the bioreactor fermentation, respectively. The successful construction of Gox and VHb fusion or complex proteins, as proposed in this study, presents promising approaches to enhance Gox catalytic efficiency and lower aerodynamic costs in gluconic acid production. KEY POINTS: • Overexpressing free VHb in A. niger did not improve the catalytic efficiency of Gox • The VHb-GS1-GoxA showed an increased Kcat/Km value by 96% than GoxA • The single-strain system worked better in the gluconic acid bioreactor fermentation.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Effects of sustained viral response on lipid in Hepatitis C: a systematic review and meta-analysis.

BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. REGISTRATION: PROSPERO CRD42020180793.

Risk factors of immune checkpoint inhibitor-related pneumonitis after neoadjuvant immunochemotherapy for resectable NSCLC.

BACKGROUND: The incidence of checkpoint inhibitor-associated pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) has been substantiated through large-scale clinical trials or real-world studies. However, reports on CIP incidence within the context of neoadjuvant immunotherapy for resectable NSCLC remain scarce. This study endeavors to investigate the incidence, risk factors, and outcomes of CIP in patients with resectable NSCLC receiving neoadjuvant immunochemotherapy. METHODS: A retrospective, case-control study was conducted on patients diagnosed with NSCLC stages IIA-IIIB who received neoadjuvant immunochemotherapy between January 2018 and September 2022. Patients were stratified into two groups based on the presence or absence of CIP, facilitating a comparative analysis of clinical characteristics, treatment modalities, physiological indicators, and prognostic outcomes . RESULTS: The study cohort comprised 245 patients, with 11.4% (28/245) experiencing CIP. The median period of CIP onset was 70 (range, 40-221) days. The incidence of severe CIP (grade 3-4) was 3.7% (9/245). Patients with CIP showed a higher all-cause mortality rate of 21.4% (6/28) compared to that of patients without CIP. Those who developed CIP exhibited elevated body mass index (BMI) values (p = 0.028) and increased fibrinogen (FIB) levels (p < 0.001), alongside a significant decrease in both diffusing capacity for carbon monoxide (DLCO)% pred (p = 0.001) and DLCO/VA% pred (p = 0.021) after neoadjuvant therapy compared to pre-indicators. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of three assessed variables (FIB levels, BMI, DLCO) reached 0.806 in predicting CIP occurrence at an early stage. CONCLUSIONS: This cohort demonstrated that elevated BMI, increased FIB levels, and decreased pulmonary diffusion function after neoadjuvant therapy are risk factors of CIP occurrence. Early assessment and continuous monitoring of these indicators are imperative for the predictive identification of CIP, enhancing patient management and outcomes.

Immune checkpoint inhibitor combined with chemotherapy versus chemotherapy alone in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: a meta-analysis of random controlled trials.

PURPOSE: Immune checkpoint inhibitor (ICI) monotherapy and chemotherapy (CT) have been used to treat recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC), with demonstrated survival benefits and good safety. However, whether combination therapy is superior to CT alone remains unclear. We summarized the existing evidence comparing the effectiveness and toxicities of ICI combined with CT versus CT alone. METHODS: Online databases was conducted for eligible randomized controlled trials (RCTs) published up to November 1, 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoint. Objective response rates (ORRs) and adverse events (AEs) were the secondary endpoint. RESULTS: Three randomized controlled trials (Capture-1st, JUPITER-02, and RATIONALE-309) were included. First-line ICI therapy combined with CT showed significant improvement in PFS (hazard ratio[HR], 0.53; 95% confidence interval[CI]: 0.44-0.64), OS (HR, 0.63;95%CI: 0.49-0.81) and ORRs (odds ratio[OR], 1.79;95%CI: 1.30-2.46), when compared with CT alone. AEs ≥ grade 3 during treatment and treatment-related deaths were not significantly different between the two groups. CONCLUSIONS: In patients with R/M-NPC, ICI therapy combined with CT showed improved ORRs, PFS, and OS, with similar safety as CT alone.

Dual-branch Transformer for semi-supervised medical image segmentation.

PURPOSE: In recent years, the use of deep learning for medical image segmentation has become a popular trend, but its development also faces some challenges. Firstly, due to the specialized nature of medical data, precise annotation is time-consuming and labor-intensive. Training neural networks effectively with limited labeled data is a significant challenge in medical image analysis. Secondly, convolutional neural networks commonly used for medical image segmentation research often focus on local features in images. However, the recognition of complex anatomical structures or irregular lesions often requires the assistance of both local and global information, which has led to a bottleneck in its development. Addressing these two issues, in this paper, we propose a novel network architecture. METHODS: We integrate a shift window mechanism to learn more comprehensive semantic information and employ a semi-supervised learning strategy by incorporating a flexible amount of unlabeled data. Specifically, a typical U-shaped encoder-decoder structure is applied to obtain rich feature maps. Each encoder is designed as a dual-branch structure, containing Swin modules equipped with windows of different size to capture features of multiple scales. To effectively utilize unlabeled data, a level set function is introduced to establish consistency between the function regression and pixel classification. RESULTS: We conducted experiments on the COVID-19 CT dataset and DRIVE dataset and compared our approach with various semi-supervised and fully supervised learning models. On the COVID-19 CT dataset, we achieved a segmentation accuracy of up to 74.56%. Our segmentation accuracy on the DRIVE dataset was 79.79%. CONCLUSIONS: The results demonstrate the outstanding performance of our method on several commonly used evaluation metrics. The high segmentation accuracy of our model demonstrates that utilizing Swin modules with different window sizes can enhance the feature extraction capability of the model, and the level set function can enable semi-supervised models to more effectively utilize unlabeled data. This provides meaningful insights for the application of deep learning in medical image segmentation. Our code will be released once the manuscript is accepted for publication.

It is time to improve the acceptance of COVID-19 vaccines among people with chronic diseases: A systematic review and meta-analysis.

This study aims to investigated COVID-19 vaccine acceptance among people with chronic diseases and the factors correlating with their vaccination hesitancy. The articles were searched in PubMed, Ovid, EMBASE, and web of science databases between December 2019 and October 2022. Cross-sectional studies, including the acceptance of the COVID-19 vaccine by patients with chronic diseases (≥18 years old), were included in this study. The outcomes included the proportion and 95% confidence interval (95% CI) of chronic disease patients willing to be vaccinated and the odds ratio (OR) and 95% CI of correlating factors. The source of heterogeneity was analyzed through meta-regression and subgroup analysis. We included 31 studies involving 57 875 patients with chronic disease. The overall COVID-19 vaccine acceptance among patients with chronic disease was 0.65 (95% CI, 0.59-0.72). The acceptance among the elderly patients was 0.53 (95% CI, 0.26-0.80). South America had the highest COVID-19 vaccine acceptance rate and Asia the lowest, while on a country level, the United Kingdom had the highest acceptance rate among patients with chronic diseases. People with rheumatic immune diseases had the lowest rate of COVID-19 vaccine acceptance. Concerns about vaccine safety had a statistically different effect on acceptance. Overall, the health systems ought to focus on educating specific groups of individuals on the benefits of COVID-19 vaccination and addressing safety concerns.

sFlt-1-enriched exosomes induced endothelial cell dysfunction and a preeclampsia-like phenotype in mice.

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by maternal endothelial dysfunction and end-organ damage. Our previous work demonstrated that PE patient-derived exosomes contained higher levels of soluble FMS-like tyrosine kinase-1 (sFlt-1) and significantly induced endothelial dysfunction and PE development. However, the mechanisms underlying the effect of sFlt-1-enriched exosomes (sFlt-1-Exo) on PE development are poorly characterized. Here, we revealed that trophoblast-derived sFlt-1-Exo treatment induced significant inhibition of human umbilical vein endothelial cell (HUVEC) migration and tube formation, as well as an increase in sFlt-1 secretion. Mechanistically, we found that the increased sFlt-1 secretion in the cell culture medium was attributed to enhanced transcription of sFlt-1 in HUVECs. Importantly, we observed that treating pregnant mice with sFlt-1-Exo or recombinant mouse sFlt-1 triggered a preeclampsia-like phenotype, characterized by elevated blood pressure, proteinuria, increased plasma sFlt-1 and adverse pregnancy outcomes. These results strongly suggested that sFlt-1-Exo-induced endothelial dysfunction could be partially attributed to the upregulation of sFlt-1 in endothelial cells, potentially leading to the development of a preeclampsia-like phenotype in mice.

Determinants of Willingness to Use PrEP Among Gay and Bisexual Men in China Before Implementation: A Structural Equation Modeling Assessment.

With the recent endorsement of PrEP by the Chinese government, research is urgently needed to better understand factors impacting PrEP uptake among gay, bisexual, and other men who have sex with men (GBMSM) in China. This study examined willingness to use PrEP for HIV prevention among GBMSM in China through structural equation modeling. We examined the relationship among PrEP-related attitudes, subjective norms, PrEP-related knowledge and beliefs about medicines and willingness to use PrEP. The analysis showed a good fit between the data and both the measurement model (RMSEA = 0.060) and structural model (RMSEA = 0.054). Knowledge, attitudes, and subjective norms were significantly related to intention to use PrEP, whereas the effect of general beliefs about medicines was insignificant. These effect mechanisms point to the importance of designing interventions to support PrEP uptake that target knowledge, enhance positive attitudes about PrEP within social networks, and build positive social norms around PrEP among sexually active GBMSM.

Evaluation of blood-based PRO-C3 testing as a diagnostic marker for staging liver fibrosis: A systematic review and meta-analysis.

BACKGROUND AND AIM: With the global increase in chronic liver disease and cirrhosis, there is an increasing need to identify non-invasive biomarkers to measure the severity of disease progression while reducing reliance on pathological biopsies. This study aimed to comprehensively evaluate the diagnostic value of PRO-C3 as a biomarker for staging liver fibrosis in patients with viral hepatitis or fatty liver disease. METHODS: Articles published until January 6, 2023, were searched in the PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate the quality of the included studies. Pooled sensitivity, specificity, diagnostic odds ratio, and likelihood ratios were integrated using a random-effects model, and a summary receiver operating characteristic curve was constructed. Publication bias was also detected. Subgroup and meta-regression analyses, as well as sensitivity analysis, were also performed. RESULTS: Fourteen studies with 4315 patients were included. Summary area under the curve of PRO-C3 for the identification of significant fibrosis (≥ F2) and advanced fibrosis (≥ F3) was 0.80 (95% confidence interval: 0.76-0.83). Subgroup and meta-regression analyses suggested that disease type and sample size may be the primary factors of heterogeneity in PRO-C3 diagnosis of ≥ F2, while study design, study sample type, and enzyme-linked immunosorbent assay kit brand may be the primary sources of heterogeneity in PRO-C3 diagnosis of ≥ F3. CONCLUSIONS: PRO-C3 demonstrated clinically meaningful diagnostic accuracy when used alone as a non-invasive biomarker for diagnosing the liver fibrosis stage in individuals with viral hepatitis or fatty liver disease.

The mediating effect of distress tolerance on the relationship between stressful life events and suicide risk in patients with major depressive disorder.

BACKGROUND: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD. METHODS: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk. RESULTS: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect. CONCLUSION: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.

Willingness to take long-acting injectable pre-exposure prophylaxis among men who have sex with men who participated in the CROPrEP study: a cross-sectional online study.

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Bedaquiline and Linezolid improve anti-TB treatment outcome in drug-resistant TB patients with HIV: A systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice. METHODS: We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality. RESULTS: 38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too. CONCLUSIONS: Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.

The benefits of psychosocial interventions for mental health in men who have sex with men living with HIV: a systematic review and meta-analysis.

OBJECTIVE: Men who have sex with men (MSM) living with HIV are more likely to suffer from mental health problems. They should be given adequate attention to treat and improve their mental health disorders. This meta-analysis aimed to assess whether psychosocial interventions reliably improve psychological well-being among MSM living with HIV. METHOD: Cochrane Library, EMBASE, PsycINFO, and PubMed were searched for psychosocial intervention randomized controlled trials evaluating mental health (e.g., depression, anxiety, self-efficacy). The effect size was pooled using the random-effects model, and continuous outcomes were reported using standardized mean difference (SMD) values . RESULTS: A total of 12 studies including 1782 participants were included in the meta-analysis. Psychosocial interventions in contrast to control groups significantly reduced depression (SMD, - 0.28; 95% CI - 0.52 - - 0.03) at the follow-up assessment and improved quality of life (SMD 0.43, 95% CI 0.23-0.63) after treatment. Psychosocial interventions also had a significant effect on measures of self-efficacy (SMD 2.22, 95% CI 0.24-4.20), and this effect was sustained until long-term follow-up (SMD 0.55, 95% CI 0.02-1.08). Subgroup analyses revealed that improvements in depression were more significant when participants possessed higher education and treatment providers used cognitive behavioral therapy (CBT). CONCLUSIONS: The findings of this study indicate that psychosocial interventions benefit the mental health of MSM living with HIV. It is necessary to conduct more research to explore characteristics that may affect treatment outcomes in the future. TRIAL REGISTRATION: This research was prospectively registered in PROSPERO ( CRD42021262567 ).

Cortical and Thalamic Interaction with Amygdala-to-Accumbens Synapses.

The nucleus accumbens shell (NAcSh) regulates emotional and motivational responses, a function mediated, in part, by integrating and prioritizing extensive glutamatergic projections from limbic and paralimbic brain regions. Each of these inputs is thought to encode unique aspects of emotional and motivational arousal. The projections do not operate alone, but rather are often activated simultaneously during motivated behaviors, during which they can interact and coordinate in shaping behavioral output. To understand the anatomic and physiological bases underlying these interprojection interactions, the current study in mice of both sexes focused on how the basolateral amygdala projection (BLAp) to the NAcSh regulates, and is regulated by, projections from the medial prefrontal cortex (mPFCp) and paraventricular nucleus of the thalamus (PVTp). Using a dual-color SynaptoTag technique combined with a backfilling spine imaging strategy, we found that all three afferent projections primarily targeted the secondary dendrites of NAcSh medium spiny neurons, forming putative synapses. We detected a low percentage of BLAp contacts closely adjacent to mPFCp or PVTp presumed synapses, and, on some rare occasions, the BLAp formed heterosynaptic interactions with mPFCp or PVTp profiles or appeared to contact the same spines. Using dual-rhodopsin optogenetics, we detected signs of dendritic summation of BLAp with PVTp and mPFCp inputs. Furthermore, high-frequency activation of BLAp synchronous with the PVTp or mPFCp resulted in a transient enhancement of the PVTp, but not mPFCp, transmission. These results provide anatomic and functional indices that the BLAp interacts with the mPFCp and PVTp for informational processing within the NAcSh.SIGNIFICANCE STATEMENT The nucleus accumbens regulates emotional and motivational responses by integrating extensive glutamatergic projections, but the anatomic and physiological bases on which these projections integrate and interact remain underexplored. Here, we used dual-color synaptic markers combined with backfilling of nucleus accumbens medium spiny neurons to reveal some unique anatomic alignments of presumed synapses from the basolateral amygdala, medial prefrontal cortex, and paraventricular nucleus of thalamus. We also used dual-rhodopsin optogenetics in brain slices, which reveal a nonlinear interaction between some, but not all, projections. These results provide compelling anatomic and physiological mechanisms through which different glutamatergic projections to the nucleus accumbens, and possibly different aspects of emotional and motivational arousal, interact with each other for final behavioral output.

Sparse Data-Driven Learning for Effective and Efficient Biomedical Image Segmentation.

Sparsity is a powerful concept to exploit for high-dimensional machine learning and associated representational and computational efficiency. Sparsity is well suited for medical image segmentation. We present a selection of techniques that incorporate sparsity, including strategies based on dictionary learning and deep learning, that are aimed at medical image segmentation and related quantification.

Salivary microbial diversity at different stages of human immunodeficiency virus infection.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) disrupts the host microbial balance. During disease progression, the oral microbial environment is altered in untreated people living with HIV/AIDS (PLWHA); however, no studies have reported changes in salivary microbial diversity during different stages of HIV infection. Therefore, in this study, we aimed to assess the relationships between immune dysfunction and changes in saliva microbiota. To this end, we collected saliva samples from 11 HIV-negative individuals and 44 PLWHA during different stages based on the Centers for Disease Control and Prevention criteria (stage 0, early stage during the first 6 months after infection; stages 1, 2, and 3 associated with CD4+ T-lymphocyte counts of ≥500, 200-499, and ≤200 or opportunistic infection, respectively). We analyzed salivary microbial community diversity using polymerase chain reaction amplification and Illumina MiSeq sequencing. We found that HIV-positive individuals had significantly greater alpha-diversity in the microbial community composition compared with HIV-negative controls (P < 0.05) except for AIDS (stage 3); however, the predominant salivary microbiota in the five groups remained similar. Porphyromonas in the four positive groups was the only genus that was significantly less abundant in the HIV-positive groups than in the control group (P < 0.05). There were some consistencies between the general abundance of salivary microbiota and AIDS disease progression. Lots of bacterial abundances in the saliva increased dramatically during the acute HIV infection (stage 0), and some of the negligible and abnormally proliferating bacteria in the asymptomatic stage showed a downward trend. Additionally, in the AIDS stage, partial inhibition was observed. Notably, Porphyromonas was closely related to the immune activation of HIV, showing a decline in abundance once infected with HIV. Solobacterium, which induces inflammation, was negatively correlated with CD4 counts. Overall, our findings provided important insights into changes in salivary microbial diversity in PLWHA.