Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Epidemiology of extrapulmonary tuberculosis in central Guangxi from 2016 to 2021.

The burden of extrapulmonary tuberculosis (EPTB) has gradually increased in recent years, but not enough epidemiological data is available from central Guangxi. To better understand the epidemiology of EPTB in central Guangxi and identify risk factors associated with them, we retrospectively investigated the epidemiology of tuberculosis (TB), especially EPTB, among patients admitted to the Chest Hospital of Guangxi Zhuang Autonomous Region between 2016 and 2021. We excluded those infected with both pulmonary tuberculosis (PTB) and EPTB, reported the proportion and incidence of PTB or EPTB, and compared the demographic characteristics and risk factors of EPTB and PTB cases using univariate and multivariate logistic regression models. Among 30,893 TB patients, 67.25% (20,774) had PTB and 32.75% (10,119) had EPTB. Among EPTB, pleural, skeletal, lymphatic, pericardial, meningeal, genitourinary, intestinal, and peritoneal TB accounted for 49.44%, 27.20%, 8.55%, 4.39%, 3.36%, 1.48%, 0.87%, and 0.79%, respectively. Patients who were younger (age < 25), from rural areas, Zhuang and other ethnic groups, and diagnosed with anemia and HIV infection were more likely to develop EPTB. However, patients with diabetes and COPD were less likely to have EPTB. From 2016 to 2021, the proportion of PTB cases decreased from 69.73 to 64.07%. The percentage of EPTB cases increased from 30.27 to 35.93%, with the largest increase in skeletal TB from 21.48 to 34.13%. The epidemiology and risk factors of EPTB in central Guangxi are different from those of PTB. The incidence of EPTB is increasing and further studies are needed to determine the reasons for it.

Anemia and opportunistic infections in hospitalized people living with HIV: a retrospective study.

BACKGROUND: There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV. METHODS: We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X2 test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia. RESULTS: Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50-199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]). CONCLUSIONS: Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV.

Metallothionein III Decreases the Proliferation of Astrocytes and Enhances Pathological Improvements in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) affects the brain and causes difficulties with cognition and emotions. At present, there are no viable therapies to halt or slow down the advancement of AD. Metallothionein III (MT-III) exhibits antioxidant and anti-inflammatory characteristics, indicating possible therapeutic benefits. This study aimed to explore the influence of MT-III on AD pathological alterations and cognitive abilities. METHODS: In this research, we employed the universally accepted AD mouse models (3xTg-AD) as test subjects and administrated vehicle or MT-III. The mice were subjected to the Morris water maze test to assess their spatial learning and memory capabilities. Moreover, to evaluate the consequent effects on neuronal groups in the hippocampus, the Nissl staining and neuronal nuclear antigen (NeuN) immunohistochemistry were used to identify the cellular morphology changes and density. Immunohistochemistry was also used to detect ß-amyloid (Aß) and glial fibrillary acidic protein (GFAP) to measure Aß accumulation and astrocyte growth. Western blot was also used to measure Tau pathology-related PHD finger protein 1 (PHF-1), phosphorylated Tau (AT-8), and total Tau protein. RESULTS: The administration of MT-III notably enhanced spatial learning and memory function in 3xTg-AD mice, as evidenced by the Morris water maze test (p < 0.01). According to immunohistochemistry and the obtained findings, it was observed that brain tissues of mice treated with MT-III showed a notable increase of Nissl bodies and NeuN intensity (p < 0.01) while a remarkable decrease in Aß accumulation and GFAP (p < 0.01). Additionally, MT-III largely decreased levels of Tau phosphorylation-related PHF-1 and AT-8 (p < 0.01) and slightly reduced the level of Tau 5 (p < 0.05). CONCLUSION: In summary, our research indicates that MT-III has the capacity to ameliorate pathological alterations in AD mouse models and safeguard their cognitive and emotional abilities. By decreasing ß-amyloid accumulation and reducing the intensity of Tau pathology, MT-III protected hippocampal subfield neurons against pathological harm. Furthermore, MT-III reduced inflammation by inhibiting abnormal proliferation of astrocytes. Of utmost importance, MT-III greatly enhanced the cognitive abilities related to spatial learning and memory in mice, suggesting its promising therapeutic properties for AD.

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus.

Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.

Smoking, alcohol consumption, and frailty: A Mendelian randomization study.

Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design. Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation. Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: ß = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: ß = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: ß = -0.090; 95% CI = -0.151 to -0.029; p = 0.003; multivariable MR ß = -0.153; 95% CI = -0.212 to -0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation. Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty.

Prediction of the risk of cytopenia in hospitalized HIV/AIDS patients using machine learning methods based on electronic medical records.

Background: Cytopenia is a frequent complication among HIV-infected patients who require hospitalization. It can have a negative impact on the treatment outcomes for these patients. However, by leveraging machine learning techniques and electronic medical records, a predictive model can be developed to evaluate the risk of cytopenia during hospitalization in HIV patients. Such a model is crucial for designing a more individualized and evidence-based treatment strategy for HIV patients. Method: The present study was conducted on HIV patients who were admitted to Guangxi Chest Hospital between June 2016 and October 2021. We extracted a total of 66 clinical features from the electronic medical records and employed them to train five machine learning prediction models (artificial neural network [ANN], adaptive boosting [AdaBoost], k-nearest neighbour [KNN] and support vector machine [SVM], decision tree [DT]). The models were tested using 20% of the data. The performance of the models was evaluated using indicators such as the area under the receiver operating characteristic curve (AUC). The best predictive models were interpreted using the shapley additive explanation (SHAP). Result: The ANN models have better predictive power. According to the SHAP interpretation of the ANN model, hypoproteinemia and cancer were the most important predictive features of cytopenia in HIV hospitalized patients. Meanwhile, the lower hemoglobin-to-RDW ratio (HGB/RDW), low-density lipoprotein cholesterol (LDL-C) levels, CD4+ T cell counts, and creatinine clearance (Ccr) levels increase the risk of cytopenia in HIV hospitalized patients. Conclusion: The present study constructed a risk prediction model for cytopenia in HIV patients during hospitalization with machine learning and electronic medical record information. The prediction model is important for the rational management of HIV hospitalized patients and the personalized treatment plan setting.

IFI27 is a potential therapeutic target for HIV infection.

BACKGROUND: Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health. METHODS: Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA. RESULTS: We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells. CONCLUSION: The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.

Screening and Identification of Human Endogenous Retrovirus-K mRNAs for Breast Cancer Through Integrative Analysis of Multiple Datasets.

Objective: Human endogenous retroviruses (HERVs) make up 8% of the human genome. HERVs are biologically active elements related to multiple diseases. HERV-K, a subfamily of HERVs, has been associated with certain types of cancer and suggested as an immunologic target in some tumors. The expression levels of HERV-K in breast cancer (BCa) have been studied as biomarkers and immunologic therapeutic targets. However, HERV-K has multiple copies in the human genome, and few studies determined the transcriptional profile of HERV-K copies across the human genome for BCa. Methods: Ninety-one HERV-K indexes with entire proviral sequences were used as the reference database. Nine raw sequencing datasets with 243 BCa and 137 control samples were mapped to this database by Salmon software. The differential proviral expression across several groups was analyzed by DESeq2 software. Results: First, the clustering of each dataset demonstrated that these 91 HERV-K proviruses could well cluster the BCa and control samples when the normal controls were normal cells or healthy donor tissues. Second, several common HERV-K proviruses that are closely related with BCa risk were significantly differentially expressed (p adj < 0.05 and absolute log2FC > 1.5) in the tissues and cell lines. Additionally, almost all the HERV-K proviruses had higher expression in BCa tissue than in healthy donor tissue. Notably, we first found the expression of 17p13.1 provirus that located with TP53 should regulate TP53 expression in ER+ and HER2+ BCa. Conclusion: The expression profiling of these 91 HERV-K proviruses can be used as biomarkers to distinguish individuals with BCa and healthy controls. Some proviruses, especially 17p13.1, were strongly associated with BCa risk. The results suggest that HERV-K expression profiles may be appropriate biomarkers and targets for BCa.

Inhibition of ASC enhances the protective role of salvianolic acid A in traumatic brain injury via inhibition of inflammation and recovery of mitochondrial function.

More than 50 million people are affected by traumatic brain injury (TBI) each year around the world, and nearly half of the population worldwide will have one or more TBI(s) in their lifetime. And in 2017, more than 1.39 billion people in China suffered from TBI, representing nearly 18% of the world population; these were mainly caused by road traffic incidents. Salvianolic acid A is a compound obtained from Salvia miltiorrhiza Bunge, which is one of the active components of many traditional Chinese medicines for the treatment of cardiovascular and cerebrovascular disease, with the effect of inhibition of inflammatory response. ASC is a critical factor in the activation of inflammation response process via promoting the maturation of caspase-1, and activation of NLPR3 under bacterial infection promotes the necrosis of cells in an ASC-dependent manner. However, few studies focus on the effect of ASC in a TBI model. In this study, we found that inhibition of ASC reduced the expression of inflammatory cytokines, and the concentration of calcium and ROS, while it increased the expression of mitochondrial function-related proteins. We further noticed that these effects were regulated by DLK2/MLK3/JNK signalling pathway and might contribute to the treatment of TBI.

Patient pathway analysis of tuberculosis diagnostic delay: a multicentre retrospective cohort study in China.

OBJECTIVES: Delay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD). METHODS: We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated. RESULTS: The median diagnostic delay was 20 days (IQR: 7-72 days), and 229 of 400 patients (57.3%, 95%CI 52.4-62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12-0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14-0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09-0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0-1 facilities than in level 2-3 facilities (p < 0.001, respectively). CONCLUSIONS: Most patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.

The different role of YKL-40 in glioblastoma is a function of MGMT promoter methylation status.

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

Relationship between female hormonal and menstrual factors and pancreatic cancer: a meta-analysis of observational studies.

The objective of this study was to assess the relationship between female hormone and menstrual factors and pancreatic cancer (PC) through a meta-analysis of observational studies. We undertook a systematic literature search up to July 10, 2014 in PubMed and EMBASE databases. Combined relative risks (RRs) were estimated by random-effects models. Subgroup analysis was performed by study design, source of control, and geographic regions. Sensitivity analyses and publication bias were utilized to evaluate the robustness of our results. A total of 27 case-control and cohort studies were retrieved for this meta-analysis. No significant associations were observed between the risk of PC and age at menarche (RR = 0.94, 95% confidence interval [CI] 0.83-1.07), age at menopause (RR = 0.98, 95% CI 0.85-1.13), hysterectomy (RR = 0.97, 95% CI 0.84-1.11), oophorectomy (RR = 1.02, 95% CI 0.82-1.26), hormone replacement therapy (RR = 0.97, 95% CI 0.87-1.08), and oral contraceptives (RR = 1.09, 95% CI 0.96-1.23). This meta-analysis of observational studies does not support the hypothesis that exogenous hormone use and menstrual factors are associated with PC.