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Background: Fungal skin diseases are common skin diseases with a heterogeneous distribution worldwide. Objectives: This study aimed to analyse the spatiotemporal trends in the burden of fungal skin diseases at global, regional, and national levels from 1990 to 2021. Methods: Based on the data obtained from the Global Burden of Disease Study (GBD) 2021, we described the incident cases, prevalent cases, number of disability‐adjusted life years (DALYs), and corresponding age‐standardised rates (ASRs) for fungal skin diseases in 1990 and 2021 by sex, age, socio‐demographic index (SDI), 21 GBD regions, and 204 countries and territories. We used Joinpoint regression analysis to assess the temporal trends in burden of fungal skin diseases during 1990 to 2021. Spearman's rank test was used to analyse the relationship between disease burden and potential factors. Results: From 1990 to 2021, the incident cases, prevalent cases, and DALYs for fungal skin diseases worldwide increased by 67.93%, 67.73%, and 66.77%, respectively. Globally, the age‐standardised incidence rate (ASIR), age‐standardised prevalence rate (ASPR), and age‐standardised DALYs rate (ASDR) for fungal skin diseases in 2021 were 21668.40 per 100,000 population (95% UI: 19601.19–23729.17), 7789.55 per 100,000 population (95% UI: 7059.28–8583.54), and 43.39 per 100,000 population (95% UI: 17.79–89.10), respectively. Between 1990 and 2021, the ASIR, ASPR, and ASDR for fungal skin diseases have modestly increased, with AAPC of 11.71% (95% confidence interval [CI]: 11.03%–12.39%), 19.24% (95% CI: 18.12%–20.36%), and 20.25% (95% CI: 19.33%–21.18%), respectively. Males experienced a higher burden of fungal skin diseases than females. The incident cases, prevalent cases, and DALYs for fungal skin diseases were highest at the age of 5–9, while the ASRs were highest among the elderly. At national level, the highest ASRs were observed in Nigeria, Ethiopia, and Mali. Overall, SDI was negatively correlated with the ASRs, whereas Global Land‐Ocean Temperature Index (GLOTI) was remarkably positively correlated with the burden of fungal skin diseases. Conclusions: Between 1990 and 2021, the global burden of fungal skin diseases has increased, causing a high disease burden worldwide, particularly in underdeveloped regions and among vulnerable population such as children and the elderly. With global warming and aging of the population, the burden of fungal skin diseases may continue to increase in the future. Targeted and specific measures should be taken to address these disparities and the ongoing burden of fungal skin diseases. [ABSTRACT FROM AUTHOR]

Background: Cryptococcosis and talaromycosis are known as 'neglected epidemics' due to their high case fatality rates and low concern. Clinically, the skin lesions of the two fungal diseases are similar and easily misdiagnosed. Therefore, this study aims to develop an algorithm to identify cryptococcosis/talaromycosis skin lesions. Methods: Skin images of tararomiasis and cryptococcosis were collected from published articles and augmented using the Python Imaging Library (PIL). Then, five deep artificial intelligence models, VGG19, MobileNet, InceptionV3, Incept ResNetV2 and DenseNet201, were developed based on the collected datasets using transfer learning technology. Finally, the performance of the models was evaluated using sensitivity, specificity, F1 score, accuracy, AUC and ROC curve. Results: In total, 159 articles (79 for cryptococcosis and 80 for talaromycosis), including 101 cryptococcosis skin lesion images and 133 talaromycosis skin lesion images, were collected for further mode construction. Five methods showed good performance for prediction but did not yield satisfactory results for all cases. Among them, DenseNet201 performed best in the validation set, followed by InceptionV3. However, InceptionV3 showed the highest sensitivity, accuracy, F1 score and AUC values in the training set, followed by DenseNet201. The specificity of DenseNet201 in the training set is better than that of InceptionV3. Conclusions: DenseNet201 and InceptionV3 are equivalent to the optimal model in these conditions and can be used in clinical settings as decision support tools for the identification and classification of skin lesions of cryptococcus/talaromycosis. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral therapy (ART) is a prerequisite to improve immunity and reduce the morbidity and mortality of people living with HIV (PLWH). To describe ART adherence and associated factors among PLWH, patients who initiated ART in Liuzhou between 1998 and 2013 were recruited. Socio-demographic characteristics, HIV infection-related characteristics and clinical tests were analyzed. Both descriptive and multi-level analyses were used to explore factors related to ART adherence of PLWH who initiated ART in Liuzhou. A total of 8433 patients were recruited in this study. The rate of adherence to ART was 84.9% in PLWH who initiated ART in Liuzhou between 1998 and 2013. The female sex, WHO clinical stage III or IV before ART initiation, longer treatment duration and higher triglyceride were positively associated with ART adherence. Meanwhile, HIV acquired by intravenous drug use, co-infection with tuberculosis and other opportunistic infections were negatively associated with ART adherence. Measures should be adopted to improve the ART adherence of PLWH who are male, acquired HIV by intravenous drug use, and are co-infected with tuberculosis and other opportunistic infections. [ABSTRACT FROM AUTHOR]

Little is known about how Talaromyces marneffei, a thermally dimorphic fungus that causes substantial morbidity and mortality in Southeast Asia, evades the human immune system. Polarization of macrophages into fungal-inhibiting M1-like and fungal-promoting M2-like types has been shown to play an important role in the innate immune response against fungal pathogens. This mechanism has not been defined for T. marneffei. Here, we demonstrated that T. marneffei promotes its survival in human macrophages by inducing them toward M2-like polarization. Our investigations of the mechanism revealed that T. marneffei infection led to SOCS3 protein degradation by inducing tyrosine phosphorylation, thereby relieving the inhibitory effect of SOCS3 on p-STAT6, a key factor for M2-like polarization. Our SOCS3-overexpression experiments showed that SOCS3 is a positive regulator of M1-like polarization and plays an important role in limiting M2-like polarization. Furthermore, we found that inhibition of the TLR9 pathway partially blocked T. marneffei-induced M2-like polarization and significantly enhanced the killing activity of macrophages against T. marneffei. Collectively, these results reveal a novel mechanism by which T. marneffei evades the immune response of human macrophages. [ABSTRACT FROM AUTHOR]

Little is known about pre-exposure prophylaxis (PrEP) awareness and willingness among male rural-to-urban migrant workers, a high-risk population of HIV infection and transmission in China. The aim of this study was to assess the awareness of and willingness to use PrEP among this vulnerable population in two cities in Guangxi Zhuang autonomous region, a province in southwestern China. A cross-sectional survey was conducted among male rural-to-urban migrant workers in Guangxi province, during June to August, 2015. Multivariable logistic regression analysis was used to examine the factors related to PrEP acceptance. Among 669 male rural-to-urban migrant workers surveyed, the HIV prevalence was 1.79%. Among the 657 HIV-negative participants, 23.0% had heard of PrEP, 1.2% had used PrEP, and 64.7% were willing to use PrEP. Being afraid of HIV/AIDS (OR = 2.08, 95%CI: 1.04–4.19) and willing to have an HIV test (OR = 3.74, 95%CI: 1.64–8.52) were associated with willingness to use PrEP. The findings suggest that among male migrant workers in Southwestern China, the awareness of and willingness to use PrEP were relatively low. Given the fact that the HIV prevalence was high among this population, more educational campaigns about PrEP and targeted interventions are necessary for this high-risk population in Guangxi. [ABSTRACT FROM AUTHOR]

In recent years, the prevalence of human immunodeficiency virus (HIV) infection among Chinese university students has increased significantly, and HIV transmission among men who have sex with men (MSM) comprises more than half of the new cases. There is still a lack of research investigating the incidence of male-to-male sex, the attitudes towards MSM, and the awareness of HIV/AIDS among university students in Guangxi, one of the HIV high-risk areas in China. Therefore, we performed a cross-sectional investigation among 578 male students, recruited by stratified sampling, in universities in Nanning, Guangxi, between January 2016 and March 2017. Researcher-administered anonymous questionnaires were completed. Self-recognition as MSM was found in 8.48% of the subjects. Compared with non-MSM, university student MSM included more people over the age of 20 (OR = 4.95), had less migration from other districts of Guangxi (OR = 0.26), and the majority were nonmedical students (OR = 8.99). In total, 63.25% of the male student participants reported a lack of acceptance of MSM, while 35.47% acknowledged barriers between themselves and acquaintances who were MSM. Overall, 67.30% of the subjects correctly answered questions related to AIDS knowledge. The proportion of MSM subjects who answered the AIDS-related questions completely correctly was significantly lower than that of non-MSM subjects (42.86% vs. 69. 57%, respectively, OR: 0.33), but the self-recognition risk of MSM was significantly higher than that of non-MSM (OR = 2.59). Risky behaviors associated with HIV infections, including smoking, alcohol consumption, drug abuse, and inconsistent condom use, were significantly higher among the MSM participants. The percentages of student's willingness to accept MC and PrEP were 70.93% and 77.51%, respectively. These results raise the alarm that university student MSM in Guangxi, China, require urgent public attention and more effective health education, including the education on MC and PrEP. [ABSTRACT FROM AUTHOR]

Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1–exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/β, RANTES, and MIP-1α/1β in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/β, RANTES, and MIP-1α/1β, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals. [ABSTRACT FROM AUTHOR]

Background Identification of new HIV infections (HIV incidence) is critical for monitoring AIDS epidemic and assessing the effectiveness of intervention measures. However, current methods for distinguishing new infections from newly diagnosed HIV-1 patients are still imperfect. We explored utilizing miRNAs as biomarker to identify HIV new infections. Methods According to the HIV-1 status and the estimated duration of infection (EDI), we enrolled participants and divided them into three groups: healthy control, new infection (within 1 year), and old infection (longer than 1 year). Participants were assigned into screening set or validation set. miRNA microarray was performed in screening set and the differentially expressed miRNAs were screened out. The differentially expressed miRNAs were further confirmed in validation set and HIV-1 IIIB-MT2 cells infection system. Results In screening set, 5 miRNAs including miR-1291, miR-3609, miR-3162-3p, miR-874-5p and miR-4258 were screened out for their differential expression in plasma among three groups. In validation set, down- trend of miR-3162-3p was validated from healthy control, new infection to old infection groups. In HIV-1 IIIB-MT2 system, the levels of miR-3162-3p also decreased along with infection duration in vitro . Sensitivity and specificity for miR-3162-3p to distinguish new infection from old infection were 100.0% and 71.43%, respectively, with the cut-off value of 0.916. Conclusion miR-3162-3p in plasma could be a potential microRNA biomarker to identify HIV new infections in HIV-1 infected patients. [ABSTRACT FROM AUTHOR]

Background: To examine the accuracy of Rapid Diagnosis of Talaromyces marneffei (RDTM) in order to improve diagnosis and treatment for clinical measures and reduce the mortality due to associated infections. Methods: In this systematic review and meta-analysis, we screened PubMed, Ovid (Cochrane library) and Web of Science, Chinese database CNKI and Wanfang for articles published between 1956 and December, 2017. Data were taken from cross-sectional studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with T. marneffei and a control cohort or a cohort with standard fungus culture. Data were extracted by two authors and checked by three for accuracy. For quality assessment, modified QUADAS-2 criteria were used. Results: The 26 included diagnostic studies enrolled 5,594 objectives in 632 patients with T. marneffei infections and 2,612 negative controls between 1996 and 2017 in Thailand, Vietnam and China. The total combined sensitivity and specificity of rapid diagnosis of T. marneffei was 0.82 (95% CI: 0.68–0.90) and 0.99 (95% CI: 0.98–1.00). According to the experimental method, the included studies can be divided into three subgroups, including PCR-based, ELISA-based and others. The results showed these three subgroups had a highly pooled specificity of 1.00 (95% CI: 0.99–1.00), 0.99 (0.98–1.00) and 0.97 (95% CI: 0.91–1.00), respectively, while combined sensitivity was 0.84 (95% CI: 0.37–0.98), 0.82 (95% CI: 0.64–0.92) and 0.77 (95% CI: 0.54–0.91), respectively. Conclusions: Although serological methods with a high specificity is essential for potential rapid diagnostic, false-negative results can be obtained in the serum samples, there is no suitable rapid serological test to refer to as is the case with TM infection. [ABSTRACT FROM AUTHOR]

Background: Female sex workers (FSW) are a population that are at high risk for HIV infection, and their HIV/AIDS knowledge levels and sexual behaviors are of concern. This study describes changes in HIV prevalence and factors associated among female sex workers in Guigang City, Guangxi, one of the highest HIV prevalence areas in China.Methods: Data were derived from an annual cross-sectional venue-based survey, 2008 to 2015, in the form of sentinel surveillance. The participants were recruited using cluster sampling. FSW aged 16 years and above who completed a questionnaire and HIV testing. Both descriptive and multi-level analyses were used to explore factors associated with changes in HIV prevalence.Results: Seven thousand four hundred ninety-six FSW were recruited in this study. HIV prevalence among FSW in Guigang City fell into two periods, one with an increasing trend (2008-2011) and one with a decline (2012-2015). Differences between these time periods included age, relationship status, HIV knowledge, consistent condom use, lifetime illicit drug use, history of sexually transmitted infection in the past year, HIV testing, receipt of a condom distribution and education program or HIV counseling and testing, and peer education services.Conclusions: Since 2012, a reduction in HIV prevalence among FSW in Guigang City has been observed. The decline of HIV prevalence was associated with coinciding changes in demographic characteristics of FSW, improvement of HIV knowledge and safer sexual behaviors, and a program that promotes condom use, HIV counseling & testing, and peer education. [ABSTRACT FROM AUTHOR]

In China, rural areas are a weak link of HIV/AIDS prevention and control. From September 2011, an innovative 'county-township-village' allied intervention was implemented in Longzhou County, Guangxi, which assigned the tasks of HIV/AIDS prevention and control to the county Centers for Disease Control and Prevention (CDC), township hospitals, and village clinics, respectively, instead of traditional intervention in which the county CDC undertook the entire work. A 6-year consecutive cross-sectional survey, including 3-year traditional intervention (2009-2011) and 3-year innovative intervention (2012-2014), was conducted to evaluate the effects of the new intervention. Compared to traditional intervention, the innovative intervention achieved positive effects in decreasing risky behaviors. Among female sex workers, condom use rate in the last month increased from 72.06% to 96.82% ( p < 0.01). Among drug users, having commercial sex rate in the last year reduced from 17.20% to 5.94% and condom use rate increased from 14.06% to 76.09% ( p < 0.01). The risk ratio of HIV infection during innovative intervention was 0.631 (95% confidence interval 0.549-0.726) compared with traditional one. Cost-effectiveness analysis indicates that innovative intervention restores each disability-adjusted life year costing an average of $124.26. Taken together, Longzhou's innovative intervention has achieved good effects on HIV/AIDS prevention and control and provides a good reference for rural China. [ABSTRACT FROM AUTHOR]

Background: Hepatitis is a serious public health problem with increasing cases and property damage in Heng County. It is necessary to develop a model to predict the hepatitis epidemic that could be useful for preventing this disease. Methods: The autoregressive integrated moving average (ARIMA) model and the generalized regression neural network (GRNN) model were used to fit the incidence data from the Heng County CDC (Center for Disease Control and Prevention) from January 2005 to December 2012. Then, the ARIMA-GRNN hybrid model was developed. The incidence data from January 2013 to December 2013 were used to validate the models. Several parameters, including mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and mean square error (MSE), were used to compare the performance among the three models. Results: The morbidity of hepatitis from Jan 2005 to Dec 2012 has seasonal variation and slightly rising trend. The ARIMA(0,1,2)(1,1,1)12 model was the most appropriate one with the residual test showing a white noise sequence. The smoothing factor of the basic GRNN model and the combined model was 1.8 and 0.07, respectively. The four parameters of the hybrid model were lower than those of the two single models in the validation. The parameters values of the GRNN model were the lowest in the fitting of the three models. Conclusions: The hybrid ARIMA-GRNN model showed better hepatitis incidence forecasting in Heng County than the single ARIMA model and the basic GRNN model. It is a potential decision-supportive tool for controlling hepatitis in Heng County. [ABSTRACT FROM AUTHOR]

It is widely accepted that N6-methyladenosine (m6A) exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduced Single-cell m6A Analysis (Scm6A), a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we first applied Scm6A to single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and calculated the m6A levels in CD4+ and CD8+ T cells. We also applied a winscore-based m6A calculation method to conduct N6-methyladenosine sequencing (m6A-seq) analysis on CD4+ and CD8+ T cells isolated through magnetic-activated cell sorting (MACS) from the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with those quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell-level m6A analysis on lung cancer tissues as well as blood samples from patients with coronavirus disease 2019 (COVID-19), and demonstrated the landscape and regulatory mechanisms of m6A in different T cell subtypes from these diseases. In summary, Scm6A is a novel, dependable, and accurate method for single-cell m6A detection and has broad applications in the realm of m6A-related research., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Background: The immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported., Methods: We conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples., Results: The pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation., Conclusions: Metabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xie, Zhou, Li, Ning, Su, Ye, Ai, Lai, Pan, Liu, Liao, Su, Li, Liang, Cui and Huang.)

Talaromyces marneffei tends to induce systemic infection in immunocompromised individuals, which is one of the causes of the high mortality. The underlying molecular mechanisms of T.marneffei -induced abnormal liver function are still poorly understood. In this study, we found that T.marneffei -infected patients could develop abnormal liver function, evidenced by reduced albumin and increased levels of aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT). T. marneffei -infected mice exhibited similar characteristics. In vitro investigations showed that T.marneffei induced the death of AML-12 cells. Furthermore, we determined that T.marneffei infection induced pyroptosis in hepatocytes of C57BL/6J mice and AML-12 cells, demonstrated by the increase of AIM2, caspase-1/-4, Gasdermin D(GSDMD) and pyroptosis-related cytokines in T.marneffei -infected mice/cells. Importantly, cell death was markedly suppressed in the presence of VX765 (an inhibitor of caspase-1/-4). Furthermore, in the presence of VX765, T.marneffei -induced pyroptosis was blocked. Nevertheless, necroptosis and apoptosis were also detected in infected animal model at 14 days post-infection. In conclusion, T.marneffei induces pyroptosis in hepatocytes through activation of the AIM2-caspase-1/-4-GSDMD axis, which may be an important cause of liver damage, and other death pathways including necroptosis and apoptosis may also be involved in the later stage of infection.

Objective: To characterise the association between duration of exposure to antiretroviral treatment (ART) and liver damage in HIV patients with an initially normal baseline liver function and without hepatitis B virus (HBV)/hepatitis C virus (HCV) infection., Methods: A retrospective cohort study was conducted in HIV-infected individuals with normal liver function parameters at ART initiation and without HBV/HCV infection, from 14 April 2004 to 13 April 2015 in Guigang city, Guangxi, China. The association between duration of ART and liver damage (grade II-IV liver enzyme elevation [LEE] and/or total bilirubin elevation [TBE]), was analysed. Cox regression was used to examine the factors related to liver damage., Results: Of 2119 eligible patients, 12.41% (263/2119) developed liver damage (grade II-IV LEE/TBE) and contributed 4.11/100 person-years crude incidence rate. The highest liver damage incidence was observed in patients with 6-12 months' ART (15.16/100 person-years). The incidence decreased to 5.56/100 person-years in patients with 12-18 months' ART and 3.13/100 person years in patients with 18-24 months' ART, and then maintained at a relatively low and stable level in patients with 2 years' ART or longer (average of 3.65/100 person-years). Cox regression analysis revealed that current WHO disease stage II, III or IV (compared with stage I) were the risk factors for liver damage, while baseline disease stage II, III (compared with stage I) and current regimen 3TC+AZT+NVP were the protective factors for liver damage., Conclusions: Liver damage always exists among HIV-infected patients on ART with normal baseline liver function and without HBV/HCV infection. Nevertheless, cumulative ART duration does not increase the risk of liver damage. ART could tend to be long-term, however, monitoring and management of liver damage among patients on ART are also important in clinical therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA-generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA-GRNN hybrid model were used to fit and predict the incidence of tuberculosis. Parameters including mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE) were used to evaluate and compare the performance of these models for fitting historical and prospective data. The new ARIMA-GRNN model had superior fit relative to both the traditional ARIMA-GRNN model and basic ARIMA model when applied to historical data and when used as a predictive model for forecasting incidence during the subsequent 6 months. Our results suggest that the new ARIMA-GRNN model may be more suitable for forecasting the tuberculosis incidence in Heng County than traditional models.