Bromodomain and Extra-Terminal Inhibitor BMS-986158 Reverses Latent HIV-1 Infection In Vitro and Ex Vivo by Increasing CDK9 Phosphorylation and Recruitment.

Latent reservoir persistence remains a major obstacle for curing human immunodeficiency virus type 1 (HIV-1) infection. Thus, strategies for the elimination of latent HIV-1 are urgently needed. As a bromodomain and extra-terminal (BET) inhibitor, BMS-986158 has been used in clinical trials for advanced solid tumors and hematological malignancies. Here, we found that BMS-986158 reactivated latent HIV-1 in three types of HIV-1 latency cells in vitro, and in combination antiretroviral therapy (cART)-treated patient-derived peripheral blood mononuclear cells ex vivo, without influencing global immune cell activation. BMS-986158 reactivated latent HIV-1 by increasing phosphorylation of CDK9 at Thr186 and promoting recruitment of CDK9 and RNA polymerase II to the HIV-1 long terminal repeat in J-Lat cells. Furthermore, BMS-986158 exerted strong synergism in reactivating latent HIV-1 when combined with prostratin and vorinostat and enhanced the antiviral activity of anti-HIV-1 drugs. Finally, BMS-986158 showed antiviral activity in an HIV-1 acute infection model, possibly by arresting the cell cycle in infected cells. Thus, these results suggest that BMS-986158 is a potential candidate for AIDS/HIV-1 therapy.

Evaluation of Machine Learning Models for Predicting Antimicrobial Resistance of Actinobacillus pleuropneumoniae From Whole Genome Sequences.

Antimicrobial resistance (AMR) is becoming a huge problem in countries all over the world, and new approaches to identifying strains resistant or susceptible to certain antibiotics are essential in fighting against antibiotic-resistant pathogens. Genotype-based machine learning methods showed great promise as a diagnostic tool, due to the increasing availability of genomic datasets and AST phenotypes. In this article, Support Vector Machine (SVM) and Set Covering Machine (SCM) models were used to learn and predict the resistance of the five drugs (Tetracycline, Ampicillin, Sulfisoxazole, Trimethoprim, and Enrofloxacin). The SVM model used the number of co-occurring k-mers between the genome of the isolates and the reference genes to learn and predict the phenotypes of the bacteria to a specific antimicrobial, while the SCM model uses a greedy approach to construct conjunction or disjunction of Boolean functions to find the most concise set of k-mers that allows for accurate prediction of the phenotype. Five-fold cross-validation was performed on the training set of the SVM and SCM model to select the best hyperparameter values to avoid model overfitting. The training accuracy (mean cross-validation score) and the testing accuracy of SVM and SCM models of five drugs were above 90% regardless of the resistant mechanism of which were acquired resistant or point mutation in the chromosome. The results of correlation between the phenotype and the model predictions of the five drugs indicated that both SVM and SCM models could significantly classify the resistant isolates from the sensitive isolates of the bacteria (p < 0.01), and would be used as potential tools in antimicrobial resistance surveillance and clinical diagnosis in veterinary medicine.

Prevalence and clinical profile of vitiligo in China: a community-based study in six cities.

Vitiligo is a common skin disease, the prevalence of which varies between races and countries. In China, no population-based study has been reported, although there have been some epidemiological studies on single cities or regions. The objective of this study was to obtain the prevalence and clinical profile of vitiligo in China. The study was conducted in 6 cities. Cluster sampling was used in selecting communities. Residents were visited at home and were asked to complete questionnaires and receive dermatological examinations. A total of 19,974 residents were visited and 17,345 valid questionnaires were obtained. The overall prevalence of vitiligo was 0.56%. Men were affected more than women (0.71% vs. 0.45%, p < 0.01). The prevalence of vitiligo increased with age. The most common type was focal vitiligo (36.1%). A positive family history was found in 9.8% of patients. Thirty-two percent of patients reported a negative impact of vitiligo on their quality of life.

Prevalence of psoriasis in China: a population-based study in six cities.

BACKGROUND: Although psoriasis occurs worldwide, the prevalence varies considerably between different peoples and regions. In China, a questionnaire-based study was carried out in 1987 and the prevalence of psoriasis was found to be 0.12%. Since then, no large-scale, population-based study has been reported. OBJECTIVES: To obtain the accurate figures for the prevalence of psoriasis in China. METHODS: A population-based survey was conducted in 6 cities. The cluster sampling method was used to select communities in each city. The subjects were required to fill out self-reporting questionnaires during a face-to-face interview and also received physical examination by dermatologists. RESULTS: 19,974 subjects were visited and 17,345 completed the questionnaires and received dermatological examination. 102 subjects (0.59%) were found to have psoriasis. After standardization, the prevalence of psoriasis was 0.47%. The prevalence of psoriasis in males and females was 0.54% and 0.44% respectively. 97.06% of the patients had psoriasis vulgaris. 28.43% of the patients reported a family history of psoriasis. 59.80% of patients experienced a negative influence on the quality of life. CONCLUSIONS: This population-based and dermatologist-confirmed study showed that the prevalence of psoriasis in China is 0.47%, which is higher than that reported in 1987.

Prevalence of acne vulgaris in Chinese adolescents and adults: a community-based study of 17,345 subjects in six cities.

Acne vulgaris is a common skin condition in adolescents. The prevalence of acne is thought to vary between ethnic groups and countries. A large-scale community-based study was performed in six cities in China to determine the prevalence and possible risk factors for acne in the Chinese population. A total of 17,345 inhabitants were included in this study. Of these, 1,399 were found to have acne. No acne was found in subjects under 10 years of age, and only 1.6% in the 10-year-old group had acne. Prevalence then increased rapidly with age, up to 46.8% in the 19-year-old group. After that, it declined gradually with age. Acne was rare in people over 50 years of age. In subjects in their late teens and 20s, acne was more prevalent in males, while in those over 30 years of age it was more prevalent in females. In subjects with acne, 68.4% had mild; 26.0% had moderate and 5.6% had severe acne. In adult acne, persistent acne was much more common (83.3%) than late-onset acne (16.7%). Smoking and drinking were found to be associated with adolescent acne, while no association was found between diet and acne. These results suggest that the prevalence of acne in the Chinese population is lower than that in Caucasian populations, and that adult acne is not uncommon in Chinese subjects.