Summarizing methods for estimating population size for key populations: a global scoping review for human immunodeficiency virus research.

BACKGROUND: Estimating the population sizes of key populations(people who inject drugs, men who have sex with men, transgender persons, and commercial sex workers) is critical for understanding the overall Human Immunodeficiency Virus burden. This scoping review aims to synthesize existing methods for population size estimation among key populations, and provide recommendations for future application of the existing methods. METHODS: Relevant studies published from 1st January 2000 to 4th August 2020 and related to key population size estimation were retrieved and 120 of 688 studies were assessed. After reading the full texts, 81 studies were further excluded. Therefore, 39 studies were included in this scoping review. Estimation methods included five digital methods, one in-person method, and four hybrid methods. FINDING: We summarized and organized the methods for population size estimateion into the following five categories: methods based on independent samples (including capture-recapture method and multiplier method), methods based on population counting (including Delphi method and mapping method), methods based on the official report (including workbook method), methods based on social network (including respondent-driven sampling method and network scale-up method) and methods based on data-driven technologies (Bayesian estimation method, Stochastic simulation method, and Laska, Meisner, and Siegel estimation method). Thirty-six (92%) articles were published after 2010 and 23 (59%) used multiple methods. Among the articles published after 2010, 11 in high-income countries and 28 in low-income countries. A total of 10 estimated the size of commercial sex workers, 14 focused on men who have sex with men, and 10 focused on people who inject drugs. CONCLUSIONS: There was no gold standard for population size estimation. Among 120 studies that were related to population size estimation of key populations, the most commonly used population estimation method is the multiplier method (26/120 studies). Every method has its strengths and biases. In recent years, novel methods based on data-driven technologies such as Bayesian estimation have been developed and applied in many surveys

Effectiveness of sexual health influencers identified by an ensemble machine learning model in promoting secondary distribution of HIV self-testing among men who have sex with men in China: study protocol for a quasi-experimental trial

Background HIV self-testing (HIVST), especially the secondary distribution of HIVST (SD-HIVST) initiated by sexual health influencers (SHIs), has been recognized as an effective strategy in promoting HIV testing, especially among men who have sex with men (MSM). This quasi-experimental study aimed to evaluate whether SHIs identified through the ensemble machine learning approach can distribute more HIVST than those who identified by the empiricalscale. Methods We will recruit eligible adults (≥18 years old) who were assigned male gender at birth, and willing to participate in potential SD-HIVST online. Participants will be assigned randomly to two groups (scale group or machine learning group), followed by a separate process of SHI identification based on the group assignment. After identification, all index participants (defined as identified SHIs who are verbally consented to participate in SD-HIVST or who directly order HIVST kits) will follow the same procedure for SD-HIVST acquisition and distribution. Index participants can order HIVST online and distribute them to members within their social networks (defined as alters) in-person or virtually through a personalized peer referral link. Once a unique alter uploads a photographed test result to the platform, both the alter and the corresponding index participant will receive a fixed incentive of 3 USD. The index MSM can order up to five HIVST in the first three months and ten HIVST in the following three months. Each index participant will need to complete a baseline survey at the first-time ordering and one to two follow-upbased on the times of ordering,, three months after ordering. This trial will be comparing 1) the mean number of alters motivated by each index participant in each group and 2) the mean number of newly-tested alters motivated by each index participant in each group. Discussion In promoting the efficacy of identifying SHIs for SD-HIVST, our study has the potential to enhance testing coverage, particularly among marginalized individuals and those who are reluctant to for HIV and other sexually transmitted infections. Trial registration We registered the study on the Chinese Clinical Trial Registry website on 4th November 2021, with registration number ChiCTR2000039632

Monetary incentives and peer referral in promoting digital network-based secondary distribution of HIV self-testing among men who have sex with men in China: study protocol for a three-arm randomized controlled trial.

BACKGROUND: Human immunodeficiency virus (HIV) testing is a crucial strategy for HIV prevention. HIV testing rates remain low among men who have sex with men (MSM) in China. Digital network-based secondary distribution is considered as an effective model to enhance HIV self-testing (HIVST) among key populations. Digital platforms provide opportunities for testers to apply for HIVST kits by themselves, and secondary distribution allows them to apply for multiple kits to deliver to their sexual partners or members within their social network. We describe a three-arm randomized controlled trial to examine the effect of monetary incentives and peer referral in promoting digital network-based secondary distribution of HIVST among MSM in China. METHODS: Three hundred MSM in China will be enrolled through a digital platform for data collection. The eligibility criteria include being biological male, 18 years of age or over, ever having had sex with another man, being able to apply for kits via the online platform, and being willing to provide personal telephone number for follow-up. Eligible participants will be randomly allocated into one of the three arms: standard secondary distribution arm, secondary distribution with monetary incentives arm, and secondary distribution with monetary incentives plus peer referral arm. Participants (defined as "index") will distribute actual HIV self-test kits to members within their social network (defined as "alter") or share referral links to encourage alters to apply HIV self-test kits by themselves. All index participants will be requested to complete a baseline survey and a 3-month follow-up survey. Both indexes and alters will complete a survey upon returning the results by taking a photo of the used kits with the unique identification number. DISCUSSION: HIV testing rates remain suboptimal among MSM in China. Innovative interventions are needed to further expand the uptake of HIV testing among key populations. The findings of the trial can provide scientific evidence and experience on promoting secondary distribution of HIVST to reach key populations who have not yet been covered by existing testing services. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1900025433) on 26, August 2019, http://www.chictr.org.cn/showproj.aspx?proj=42001. Prospectively registered

Comparison between HIV self-testing and facility-based HIV testing approach on HIV early detection among men who have sex with men: A cross-sectional study

Background To assess whether HIV self-testing (HIVST) has a better performance in identifying HIV-infected cases than the facility-based HIV testing (HIVFBT) approach. Methods A cross-sectional study was conducted among men who have sex with men (MSM) by using an online questionnaire (including information on sociodemographic, sexual biography, and HIV testing history) and blood samples (for limiting antigen avidity enzyme immunoassay, gene subtype testing, and taking confirmed HIV test). MSM who were firstly identified as HIV positive through HIVST and HIVFBT were compared. Chi-square or Fisher’s exact test was used to explore any association between both groups and their subgroups. Results In total, 124 MSM HIV cases were identified from 2017 to 2021 in Zhuhai, China, including 60 identified through HIVST and 64 through HIVFBT. Participants in the HIVST group were younger (≤30 years, 76.7% vs. 46.9%), were better educated (>high school, 61.7% vs. 39.1%), and had higher viral load (≥1,000 copies/ml, 71.7% vs. 50.0%) than MSM cases identified through HIVFBT. The proportion of early HIV infection in the HIVST group was higher than in the HIVFBT group, identified using four recent infection testing algorithms (RITAs) (RITA 1, 46.7% vs. 25.0%; RITA 2, 43.3% vs. 20.3%; RITA 3, 30.0% vs. 14.1%; RITA 4, 26.7% vs. 10.9%; all p < 0.05). Conclusions The study showed that HIVST has better HIV early detection among MSM and that recent HIV infection cases mainly occur in younger and better-educated MSM. Compared with HIVFBT, HIVST is more accessible to the most at-risk population on time and tends to identify the case early. Further implementation studies are needed to fill the knowledge gap on this medical service model among MSM and other target populations

Oroxylin A promotes PTEN-mediated negative regulation of MDM2 transcription via SIRT3-mediated deacetylation to stabilize p53 and inhibit glycolysis in wt-p53 cancer cells

Introduction p53 plays important roles in regulating the metabolic reprogramming of cancer, such as aerobic glycolysis. Oroxylin A is a natural active flavonoid with strong anticancer effects both in vitro and in vivo. Methods wt-p53 (MCF-7 and HCT116 cells) cancer cells and p53-null H1299 cancer cells were used. The glucose uptake and lactate production were analyzed using Lactic Acid production Detection kit and the Amplex Red Glucose Assay Kit. Then, the protein levels and RNA levels of p53, mouse double minute 2 (MDM2), and p53-targeted glycolytic enzymes were quantified using Western blotting and quantitative polymerase chain reaction (PCR), respectively. Immunoprecipitation were performed to assess the binding between p53, MDM2, and sirtuin-3 (SIRT3), and the deacetylation of phosphatase and tensin homolog (PTEN). Reporter assays were performed to assess the transcriptional activity of PTEN. In vivo, effects of oroxylin A was investigated in nude mice xenograft tumor-inoculated MCF-7 or HCT116 cells. Results Here, we analyzed the underlying mechanisms that oroxylin A regulated p53 level and glycolytic metabolism in wt-p53 cancer cells, and found that oroxylin A inhibited glycolysis through upregulating p53 level. Oroxylin A did not directly affect the transcription of wt-p53, but suppressed the MDM2-mediated degradation of p53 via downregulating MDM2 transcription in wt-p53 cancer cells. In further studies, we found that oroxylin A induced a reduction in MDM2 transcription by promoting the lipid phosphatase activity of phosphatase and tensin homolog, which was upregulated via sirtuin3-mediated deacetylation. In vivo, oroxylin A inhibited the tumor growth of nude mice-inoculated MCF-7 or HCT116 cells. The expression of MDM2 protein in tumor tissue was downregulated by oroxylin A as well. Conclusions These results provide a p53-independent mechanism of MDM2 transcription and reveal the potential of oroxylin A on glycolytic regulation in both wt-p53 and mut-p53 cancer cells. The studies have important implications for the investigation on anticancer effects of oroxylin A, and provide the academic basis for the clinical trial of oroxylin A in cancer patients

Monetary incentives and peer referral in promoting secondary distribution of HIV self-testing among men who have sex with men in China: A randomized controlled trial

Background Digital network–based methods may enhance peer distribution of HIV self-testing (HIVST) kits, but interventions that can optimize this approach are needed. We aimed to assess whether monetary incentives and peer referral could improve a secondary distribution program for HIVST among men who have sex with men (MSM) in China. Methods and findings Between October 21, 2019 and September 14, 2020, a 3-arm randomized controlled, single-blinded trial was conducted online among 309 individuals (defined as index participants) who were assigned male at birth, aged 18 years or older, ever had male-to-male sex, willing to order HIVST kits online, and consented to take surveys online. We randomly assigned index participants into one of the 3 arms: (1) standard secondary distribution (control) group (n = 102); (2) secondary distribution with monetary incentives (SD-M) group (n = 103); and (3) secondary distribution with monetary incentives plus peer referral (SD-M-PR) group (n = 104). Index participants in 3 groups were encouraged to order HIVST kits online and distribute to members within their social networks. Members who received kits directly from index participants or through peer referral links from index MSM were defined as alters. Index participants in the 2 intervention groups could receive a fixed incentive ($3 USD) online for the verified test result uploaded to the digital platform by each unique alter. Index participants in the SD-M-PR group could additionally have a personalized peer referral link for alters to order kits online. Both index participants and alters needed to pay a refundable deposit ($15 USD) for ordering a kit. All index participants were assigned an online 3-month follow-up survey after ordering kits. The primary outcomes were the mean number of alters motivated by index participants in each arm and the mean number of newly tested alters motivated by index participants in each arm. These were assessed using zero-inflated negative binomial regression to determine the group differences in the mean number of alters and the mean number of newly tested alters motivated by index participants. Analyses were performed on an intention-to-treat basis. We also conducted an economic evaluation using microcosting from a health provider perspective with a 3-month time horizon. The mean number of unique tested alters motivated by index participants was 0.57 ± 0.96 (mean ± standard deviation [SD]) in the control group, compared with 0.98 ± 1.38 in the SD-M group (mean difference [MD] = 0.41),and 1.78 ± 2.05 in the SD-M-PR group (MD = 1.21). The mean number of newly tested alters motivated by index participants was 0.16 ± 0.39 (mean ± SD) in the control group, compared with 0.41 ± 0.73 in the SD-M group (MD = 0.25) and 0.57 ± 0.91 in the SD-M-PR group (MD = 0.41), respectively. Results indicated that index participants in intervention arms were more likely to motivate unique tested alters (control versus SD-M: incidence rate ratio [IRR = 2.98, 95% CI = 1.82 to 4.89, p-value < 0.001; control versus SD-M-PR: IRR = 3.26, 95% CI = 2.29 to 4.63, p-value < 0.001) and newly tested alters (control versus SD-M: IRR = 4.22, 95% CI = 1.93 to 9.23, p-value < 0.001; control versus SD-M-PR: IRR = 3.49, 95% CI = 1.92 to 6.37, p-value < 0.001) to conduct HIVST. The proportion of newly tested testers among alters was 28% in the control group, 42% in the SD-M group, and 32% in the SD-M-PR group. A total of 18 testers (3 index participants and 15 alters) tested as HIV positive, and the HIV reactive rates for alters were similar between the 3 groups. The total costs were $19,485.97 for 794 testers, including 450 index participants and 344 alter testers. Overall, the average cost per tester was$24.54, and the average cost per alter tester was $56.65. Monetary incentives alone (SD-M group) were more cost-effective than monetary incentives with peer referral (SD-M-PR group) on average in terms of alters tested and newly tested alters, despite SD-M-PR having larger effects. Compared to the control group, the cost for one more alter tester in the SD-M group was$14.90 and $16.61 in the SD-M-PR group. For newly tested alters, the cost of one more alter in the SD-M group was$24.65 and $49.07 in the SD-M-PR group. No study-related adverse events were reported during the study. Limitations include the digital network approach might neglect individuals who lack internet access. Conclusions Monetary incentives alone and the combined intervention of monetary incentives and peer referral can promote the secondary distribution of HIVST among MSM. Monetary incentives can also expand HIV testing by encouraging first-time testing through secondary distribution by MSM. This social network–based digital approach can be expanded to other public health research, especially in the era of the Coronavirus Disease 2019 (COVID-19). Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR190002543

The Genome of Ganderma lucidum Provide Insights into Triterpense Biosynthesis and Wood Degradation

BACKGROUND: Ganoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: The genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi. CONCLUSIONS/SIGNIFICANCE: The genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy