A Machine Learning Model for Identifying Sexual Health Influencers to Promote the Secondary Distribution of HIV Self-Testing Among Gay, Bisexual, and Other Men Who Have Sex With Men in China: Quasi-Experimental Study.

BACKGROUND: Sexual health influencers (SHIs) are individuals actively sharing sexual health information with their peers, and they play an important role in promoting HIV care services, including the secondary distribution of HIV self-testing (SD-HIVST). Previous studies used a 6-item empirical leadership scale to identify SHIs. However, this approach may be biased as it does not consider individuals' social networks. OBJECTIVE: This study used a quasi-experimental study design to evaluate how well a newly developed machine learning (ML) model identifies SHIs in promoting SD-HIVST compared to SHIs identified by a scale whose validity had been tested before. METHODS: We recruited participants from BlueD, the largest social networking app for gay men in China. Based on their responses to the baseline survey, the ML model and scale were used to identify SHIs, respectively. This study consisted of 2 rounds, differing in the upper limit of the number of HIVST kits and peer-referral links that SHIs could order and distribute (first round ≤5 and second round ≤10). Consented SHIs could order multiple HIV self-testing (HIVST) kits and generate personalized peer-referral links through a web-based platform managed by a partnered gay-friendly community-based organization. SHIs were encouraged to share additional kits and peer-referral links with their social contacts (defined as "alters"). SHIs would receive US $3 incentives when their corresponding alters uploaded valid photographic testing results to the same platform. Our primary outcomes included (1) the number of alters who conducted HIVST in each group and (2) the number of newly tested alters who conducted HIVST in each. We used negative binomial regression to examine group differences during the first round (February-June 2021), the second round (June-November 2021), and the combined first and second rounds, respectively. RESULTS: In January 2021, a total of 1828 men who have sex with men (MSM) completed the survey. Overall, 393 SHIs (scale=195 and ML model=198) agreed to participate in SD-HIVST. Among them, 229 SHIs (scale=116 and ML model=113) ordered HIVST on the web. Compared with the scale group, SHIs in the ML model group motivated more alters to conduct HIVST (mean difference [MD] 0.88, 95% CI 0.02-2.22; adjusted incidence risk ratio [aIRR] 1.77, 95% CI 1.07-2.95) when we combined the first and second rounds. Although the mean number of newly tested alters was slightly higher in the ML model group than in the scale group, the group difference was insignificant (MD 0.35, 95% CI -0.17 to -0.99; aIRR 1.49, 95% CI 0.74-3.02). CONCLUSIONS: Among Chinese MSM, SHIs identified by the ML model can motivate more individuals to conduct HIVST than those identified by the scale. Future research can focus on how to adapt the ML model to encourage newly tested individuals to conduct HIVST. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2000039632; https://www.chictr.org.cn/showprojEN.html?proj=63068. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-021-11817-2.

Homoprejudiced Violence Experiences and High-Risk Sexual Behaviors among Chinese Men Who Have Sex with Men: Depression Severity and Recreational Drug Usage as Potential Mediators.

Homoprejudiced violence is a type of aggression against an individual or a community based on their actual or perceived sexual orientation. It may be linked to risks of acquiring HIV/STI via psychosocial variables. This study explored the association between homoprejudiced violence experiences and high-risk sexual behaviors, and potential psychosocial mediators. Using cross-sectional survey data collected in China through Blued among men who have sex with men (MSM) in January 2021, this study conducted multiple mediation analyses. Standard instruments were used to collect data on depressive symptoms in the last two weeks (PHQ-9), recreational drug usage in the last three months, and ever experiencing homoprejudiced violence (12-item survey instrument). Dependent variables were having condomless anal sex and having three or more sexual partners in the last three months. Among 1828 MSM, nearly half (847, 46%) had experienced homoprejudiced violence. Twenty-three percent (427) reached a score that suggested moderate or severe depression and 35% (644) had used recreational drugs. In the last three months, 40% (731) had condomless anal sex and 34% (626) had three or more sexual partners. The indirect mediational coefficients through depression on condomless anal sex and multiple sexual partners were 0.04 (95% CI: [0.02, 0.07]) and 0.02 (95% CI: [0.001, 0.05]), respectively. The indirect mediational coefficient of homoprejudiced violence experience on multiple sexual partners through recreational drug use was 0.05 (95% CI: [0.03, 0.08]). These findings suggest that more comprehensive interventions are needed to address the syndemic of homoprejudiced violence, mental health issues, and HIV/STI-related risks.

Factors Associated with the First-time HIV Testing Among Chinese men who have sex with men Who Received HIV Self-tests from Partners or Friends.

Secondary distribution of HIV self-testing (HIVST) among individual social networks was an effective approach to expanding HIV testing among men who have sex with men (MSM). However, understanding the factors associated with first-time HIV testing behaviors in the secondary distribution of HIVST programs is limited. Hence, this study aims to identify factors related to first-time testers in the secondary distribution of HIVST. Participants were recruited from five provinces in southern China through Blued, a geo-social gay networking app in China from January 2021 to December 2021. Eligible consented participants (referred to as "seeds") finished a baseline survey and then applied for up to five HIVST kits. They were encouraged to distribute HIVST kits to other MSM (referred to as "alters") and alters were encouraged to scan a QR code to return their photographed testing results. All alters were invited to finish an online survey. In total, 229 seeds reached 292 alters, among whom 126 (43.2%) were first-time testers whereas 166 (56.8%) were non-first-time testers. Importantly, our results demonstrated that the first-time HIV testers were more likely to self-report as heterosexual (aOR = 4.88, 95% CI 1.01-23.61), disclose sexual orientation and/or SSB (aOR = 1.73, 95% CI 1.01-2.96), and receive HIVST knowledge from the seeds (aOR = 3.25, 95% CI 1.02-10.34). However, those who had sex with male partners in the last three months were less likely to be first-time testers (aOR = 0.43, 95% CI 0.23-0.82). Practical implications and limitations were also discussed to improve future HIV prevention programs.

Ultra-Processed Food Consumption and Mortality: Three Cohort Studies in the United States and United Kingdom.

INTRODUCTION: Given the increase in ultra-processed food (UPF) consumption, their potential health effects have aroused concern. Whether UPF consumption is associated with cancer and cardiovascular disease mortality is debatable. This study evaluates the association of UPF consumption with mortality. METHODS: A total of 108,714 U.S. adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (1993-2001), 208,051 UK adults from UK Biobank (2006-2010), and 41,070 U.S. adults from National Health and Nutrition Examination Survey (1999-2018) were included. Dietary data were collected by dietary questionnaire and classified using the NOVA classification. UPF consumption was expressed as the weight proportion of UPFs in total foods consumed. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs. Mediation analysis was used to evaluate whether multiple metabolic pathways mediated the associations in UK Biobank. Analyses were performed in 2022-2023. RESULTS: Combined analyses of the three cohorts showed that those with the highest quartile of UPF consumption had higher risks of all-cause mortality (hazard ratio, 1.16; 95% CI, 1.11-1.20) and cardiovascular disease mortality (hazard ratio, 1.17; 95% CI, 1.06-1.28) compared to the lowest quartile of UPF consumption. UPF consumption was not associated with cancer mortality risk. Biomarkers of liver function have the greatest mediating effects on all-cause mortality (20.3%), and biomarkers of inflammation have the greatest mediating effects on cardiovascular disease mortality (29.2%). CONCLUSIONS: Higher UPF consumption was associated with increased all-cause and cardiovascular disease mortality risk, with multiple metabolic pathways playing mediating roles.

Time trends of 16 modifiable risk factors on the burden of major cancers among the Chinese population.

The cancer burden in China is increasing. We aimed to assess the time trends in the prevalence of 16 modifiable risk factors involved in lifestyle, diet, infection, and air pollution between 1997 and 2025 based on the China Health and Nutrition Survey, the Global Burden of Disease website, and publically available studies. The population attributable fraction (PAF) and its 95% uncertainty interval (UI) from 2007 to 2035 were calculated to quantify the attributable cancer burden in major 12 anatomic sites using the comparative risk assessment method, considering a 10-year lag effect. As a result, 1,559,476 cancer cases (PAF = 54.1%, 95% UI: 36.8%-65.8%) from the 12 anatomic sites were attributable to these modifiable risk factors in 2007, with lung, liver, and gastric cancer raging the top three. It was predicted that by 2035, the attributable cancer cases would reach 1,680,098 (PAF = 44.2%, 95% UI: 29.1%-55.5%), with the top three of lung, liver, and colorectal cancer. Smoking, physical inactivity, insufficient fruit consumption, HBV infection, and Helicobacter pylori infection were the most attributable risk factors in 2007, contributing to 480,352, 233,684, 215,009, 214,455, and 187,305 associated cancer cases, respectively. In 2035, the leading factors for cancer would be smoking, physical inactivity, insufficient fruit intake, HPV infection, and HBV infection, resulting in 427,445, 424,327, 185,144, 156,535, and 154,368 cancer cases, respectively. Intervention strategies should be swiftly established and dynamically altered in response to risk factors like smoking, physical inactivity, poor fruit intake, and infectious factors that may cause a high cancer burden in the Chinese population.

Identification of Key Influencers for Secondary Distribution of HIV Self-Testing Kits Among Chinese Men Who Have Sex With Men: Development of an Ensemble Machine Learning Approach.

BACKGROUND: HIV self-testing (HIVST) has been rapidly scaled up and additional strategies further expand testing uptake. Secondary distribution involves people (defined as "indexes") applying for multiple kits and subsequently sharing them with people (defined as "alters") in their social networks. However, identifying key influencers is difficult. OBJECTIVE: This study aimed to develop an innovative ensemble machine learning approach to identify key influencers among Chinese men who have sex with men (MSM) for secondary distribution of HIVST kits. METHODS: We defined three types of key influencers: (1) key distributors who can distribute more kits, (2) key promoters who can contribute to finding first-time testing alters, and (3) key detectors who can help to find positive alters. Four machine learning models (logistic regression, support vector machine, decision tree, and random forest) were trained to identify key influencers. An ensemble learning algorithm was adopted to combine these 4 models. For comparison with our machine learning models, self-evaluated leadership scales were used as the human identification approach. Four metrics for performance evaluation, including accuracy, precision, recall, and F1-score, were used to evaluate the machine learning models and the human identification approach. Simulation experiments were carried out to validate our approach. RESULTS: We included 309 indexes (our sample size) who were eligible and applied for multiple test kits; they distributed these kits to 269 alters. We compared the performance of the machine learning classification and ensemble learning models with that of the human identification approach based on leadership self-evaluated scales in terms of the 2 nearest cutoffs. Our approach outperformed human identification (based on the cutoff of the self-reported scales), exceeding by an average accuracy of 11.0%, could distribute 18.2% (95% CI 9.9%-26.5%) more kits, and find 13.6% (95% CI 1.9%-25.3%) more first-time testing alters and 12.0% (95% CI -14.7% to 38.7%) more positive-testing alters. Our approach could also increase the simulated intervention's efficiency by 17.7% (95% CI -3.5% to 38.8%) compared to that of human identification. CONCLUSIONS: We built machine learning models to identify key influencers among Chinese MSM who were more likely to engage in secondary distribution of HIVST kits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900025433; https://www.chictr.org.cn/showproj.html?proj=42001.

Exploring adequate CO2 elevation for optimum tomato growth and yield under protected cultivation.

The adequate elevation of CO2 concentrations (e [CO2]) could not be assessed by constrained analysis of comparative experimental study for optimum plant growth and yield with improved fruit quality owing to the lack of conjunctive investigation of plant parametric responses. Instead, the principal component analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS) assessed and quantified the parametric plant responses to identify the adequate level of e [CO2] for optimum plant growth and yield. In this study, tomato plants were grown under an ambient CO2 (a [CO2], 500 µmol mol-1) and three e [CO2] (700, 850 and 1000 µmol mol-1): named EC700, EC850 and EC1000, respectively, in autumn-winter (AW) 2020 and spring summer (SS) 2021 growing seasons to investigate and evaluate the plant parametric responses under e [CO2]. The tomato plant's response with maximum transportability of biomass to fruits was observed under 700 µmol mol-1. The plant height, stem diameter and LAI were enhanced compared to a [CO2] at the optimum level under 1000 µmol mol-1 (by 50.53, 20.98 and 44.44%) and 700 µmol mol-1 (by 22.41, 12.09 and 26.88%) in Aw 2020; Ss 2021, respectively. The optimum yield was increased under 700 µmol mol-1 by 73.95% and 55.58% in Aw 2020; Ss 2021, respectively. EC700 was ranked as a priority by TOPSIS with 0.632 and 0.694 plant response performance index in Aw 2020; Ss 2021, respectively, to get optimum tomato growth, yield, water use efficiency and fruit quality. The results of this study are beneficial for commercial greenhouse crop production by fumigating the adequate level of e [CO2], to reduce the cost of CO2 fertigation, enhance the yield and save the water quantity.

Potential impact of time trend of whole grain intake on burden of major cancers in China.

Numerous studies have revealed associations between high intake of whole grains and reduced risk of various cancers. Yet, in recent decades, the traditional Chinese diets have been challenged by reduction in whole grains and increase in refined grains. To assess the impact of this dietary transition on cancer prevention, we analyzed the time trend of whole grain intake using nationally representative sampling data of over 15 thousand individuals from the China Health and Nutrition Survey. We applied the comparative risk assessment method to estimate the population attributable fraction of cancers due to insufficient whole grain intake from 1997 to 2011 and projected the trend of whole grain intake and the associated burden of cancers to 2035. We found a significant decrease of approximately 59% of whole grain intake in the Chinese population from 1997 to 2011. Compared with 1997, insufficient intake of whole grains was responsible for 9940 more cases of breast cancer, 12,903 more cases of colorectal cancer and 434 more cases of pancreatic cancer in 2011. Our projections suggest that if every Chinese would consume 125 g whole grain per day as recommended by the latest Chinese Dietary Guidelines, 0.63% bladder cancer, 8.98% breast cancer, 15.85% colorectal cancer, 3.86% esophageal cancer, 2.52% liver cancer and 2.22% pancreatic cancer (totaling 186,659 incident cases) could theoretically be averted by 2035. Even if everyone maintained the 2011 whole grain intake level, an estimated 8.38% of cancer events could still be prevented by 2035.

Self-sampled specimens demonstrate comparable accuracy and consistency to clinician-sampled specimens for HPV detection among men who have sex with men in China.

OBJECTIVES: Despite a high risk of human papillomavirus (HPV) infection among men who have sex with men (MSM), few have ever tested. This study aimed to evaluate the feasibility and accuracy of HPV self-sampling among Chinese MSM, with the purpose of measuring the feasibility of self-sampling as an alternative in HPV testing scenarios. METHODS: Eligible participants were those who were assigned male at birth, aged 18 or above, had sex with men in the past year and had never gotten HPV vaccine. Participants followed the instructions to self-sample and were also clinician-sampled from the same anatomical sites (oral fluid, penis and rectum) in both approaches. All specimens were processed using multiplex PCR assay. The reference standard of an individual with a true positive for HPV is determined via PCR test, regardless of sampling methods. Sensitivity and specificity were calculated for each approach independently and kappa test was used to assess the consistency between the two approaches. RESULTS: Overall, 211 MSM were recruited at the local clinic from April to October 2020 in Zhuhai, China. The mean age was 31 years old. Only 3% of the participants sought help from healthcare providers during self-sampling. The prevalence of HPV was 49% (103 of 211). Clinician sampling detected 91 of 103 MSM infected with HPV, with a sensitivity of 88.3% (95% CI 80.2 to 93.6) and a specificity of 100.0% (95% CI 95.7 to 100.0). Self-sampling detected 81 of 103 MSM infected with HPV, with a sensitivity of 78.6% (95% CI 69.2 to 85.9) and a specificity of 100.0% (95% CI 95.7 to 100.0). The level of agreement was moderate between clinician sampling and self-sampling (k=0.67). CONCLUSIONS: Self-sampled HPV testing demonstrated comparable accuracy and consistency to clinician sampling among MSM in China. It holds the potential to complement sexual health services especially among key populations.

Testing Together Behaviors in Secondary Distribution of HIV/Syphilis Self-testing Program Among Men Who have Sex with Men in China.

HIV self-testing (HIVST) is recommended as a promising way to increase HIV testing uptake among MSM. MSM sometimes used HIVST kits together with their sexual partners or friends. However, limited data was reported on MSM's testing together behaviors with sexual partners and non-sexual contacts. Data were collected among MSM in China from June 2018 to June 2019. Eligible participants (referred to as "index participants") finished a baseline survey and applied for HIVST kits. They were encouraged to distribute the kits to other people (referred to as "alters"). Index participants finished a 3-month follow-up survey on the distribution and usage of the kits. Alters finished an online survey on the usage of HIVST kits after they returned the photographed testing results. Results were reported based on index participants and alters, respectively. Based on follow-up data, 138 index participants successfully motivated others for HIVST, most of them (77.5%) tested together with at least one alter. Around half of alters (52.3%) reported testing together with index participants. Index participants distributed more HIVST kits to friends than sexual partners. MSM who had ever tested for HIV were more likely to test together. Our study demonstrated that the testing together behaviors during HIVST distribution among sexual partners and social network contacts were common. The social network-based approach is essential in promoting testing together and HIV status disclosure among MSM.

The Role of Chloride Channels in Plant Responses to NaCl.

Chloride (Cl-) is considered a crucial nutrient for plant growth, but it can be a challenge under saline conditions. Excessive accumulation of Cl- in leaves can cause toxicity. Chloride channels (CLCs) are expressed in the inner membranes of plant cells and function as essential Cl- exchangers or channels. In response to salt stress in plants, CLCs play a crucial role, and CLC proteins assist in maintaining the intracellular Cl- homeostasis by sequestering Cl- into vacuoles. Sodium chloride (NaCl) is the primary substance responsible for causing salt-induced phytotoxicity. However, research on plant responses to Cl- stress is comparatively rare, in contrast to that emphasizing Na+. This review provides a comprehensive overview of the plant response and tolerance to Cl- stress, specifically focusing on comparative analysis of CLC protein structures in different species. Additionally, to further gain insights into the underlying mechanisms, the study summarizes the identified CLC genes that respond to salt stress. This review provides a comprehensive overview of the response of CLCs in terrestrial plants to salt stress and their biological functions, aiming to gain further insights into the mechanisms underlying the response of CLCs in plants to salt stress.

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.

A randomized controlled trial enhancing viral hepatitis testing in primary care via digital crowdsourced intervention.

Despite the availability of hepatitis B virus (HBV) and hepatitis C virus (HCV) testing in primary care, testing rates in China remain low. Social media is an inexpensive means of disseminating information and could facilitate hepatitis testing promotion. We evaluated the capacity of digitally crowdsourced materials to promote HBV/HCV testing uptake via a randomized controlled trial (identifier: ChiCTR1900025771), which enrolled 750 Chinese primary care patients. We randomized patients (1:1) to receive crowdsourced HBV/HCV promotion materials through social media or facility-based care without promotional materials for four weeks. Exposure to all intervention materials was associated with increased odds of HBV (aOR = 1.79, 95% CI: 1.09-3.00) and HCV (aOR = 1.95, 95% CI: 1.29-2.99) testing compared to facility-based care. There was a significant reduction in hepatitis stigma among intervention group participants (HBV slope: -0.15, p < 0.05; and HCV slope: -0.13, p < 0.05). Digitally crowdsourced promotion messages could enhance hepatitis testing uptake and should be considered in hepatitis reduction strategies.Trial registration: Chinese Clinical Trial Registry (ChiCTR1900025771) on September 9, 2019. Available from: http://www.chictr.org.cn/showproj.aspx?proj=42788.

Comparing the effectiveness of secondary distribution of HIV/syphilis dual self-testing to testing card referral in promoting HIV testing among gay, bisexual, and other men who have sex with men in Guangzhou, China: a quasi-experimental study.

BACKGROUND: Social network approaches to testing allow individuals (indexes) to distribute tests to social networks (alters). This quasi-experimental study compared two social network-based testing strategies in promoting human immunodeficiency virus (HIV) testing among Chinese gay, bisexual, and other men who have sex with men (GBMSM). METHODS: GBMSM aged ≥18years were recruited from Guangzhou, China. From May to September 2019, indexes could distribute blood-based HIV/syphilis dual self-testing kits to people within their social network. Indexes recruited from October 2019 to January 2020 could send HIV testing cards to their social networks for free facility-based tests. Alters were encouraged to upload a photo verification of test results. Indexes and alters received incentives during both periods. RESULTS: There were 245 participants who were assessed for eligibility and 208/245 (84.9%) were eligible. 106 and 102 indexes were recruited in the secondary distribution and testing card arms respectively. 154/208 (74.0%) completed follow up at 1 month. 92 indexes in the secondary distribution arm self-reported distributions to 179 unique alters, and 62 in the testing card arm to 26 unique alters. An average of 1.95 (standard deviation [s.d.]=1.90) HIV/syphilis dual self-tests and 0.42 (s.d.=0.78) HIV testing cards were distributed, generating a risk difference of 1.53 (95% confidence interval [CI] 1.09, 1.96). Indexes self-identifying as gay (P =0.007) or having previously tested (P =0.02) distributed more tests. Secondary distribution cost less per alter tested (USD120 vs USD9408). CONCLUSIONS: Secondary distribution engaged more GBMSM to distribute tests and reached more GBMSM to test compared to referral cards, suggesting advantage in facilitating testing uptake among Chinese GBMSM.

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) ChiCTR1900025433.

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.

Optimal resource allocation in HIV self-testing secondary distribution among Chinese MSM: data-driven integer programming models.

Human immunodeficiency virus self-testing (HIVST) is an innovative and effective strategy important to the expansion of HIV testing coverage. Several innovative implementations of HIVST have been developed and piloted among some HIV high-risk populations like men who have sex with men (MSM) to meet the global testing target. One innovative strategy is the secondary distribution of HIVST, in which individuals (defined as indexes) were given multiple testing kits for both self-use (i.e.self-testing) and distribution to other people in their MSM social network (defined as alters). Studies about secondary HIVST distribution have mainly concentrated on developing new intervention approaches to further increase the effectiveness of this relatively new strategy from the perspective of traditional public health discipline. There are many points of HIVST secondary distribution in which mathematical modelling can play an important role. In this study, we considered secondary HIVST kits distribution in a resource-constrained situation and proposed two data-driven integer linear programming models to maximize the overall economic benefits of secondary HIVST kits distribution based on our present implementation data from Chinese MSM. The objective function took expansion of normal alters and detection of positive and newly-tested 'alters' into account. Based on solutions from solvers, we developed greedy algorithms to find final solutions for our linear programming models. Results showed that our proposed data-driven approach could improve the total health economic benefit of HIVST secondary distribution. This article is part of the theme issue 'Data science approaches to infectious disease surveillance'.

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 .

Size changes in miR­21 knockout mice: Geometric morphometrics on teeth, alveolar bone and mandible.

MicroRNA­21 (miR­21) is a small non­coding RNA that is differentially expressed during tooth development, particularly during amelogenesis. Although orthodontic tooth movement and the innate immune response are impaired, miR­21 knockout mice demonstrate no obvious skeletal phenotype. However, the consequence of miR­21 knockout on tooth phenotype and corresponding alveolar bone is unknown. The current study utilized landmark­based geometric morphometrics to identify anatomical dissimilarities of the three lower and upper molars, and the corresponding alveolar bone, in miR­21 knockout and wild­type control mice. The anatomical structures were visualized by microcomputer tomography. A total of 36 and 38 landmarks were placed on mandibular and maxillary molars, respectively. For the alveolar bone, 16 landmarks were selected on both anatomical sites. General Procrustes analysis revealed significantly smaller molars and dimensions of the alveolar bone in the mandible of the miR­21 knockout mice when compared with wild­type controls (P=0.03 and P=0.04, respectively). The overall dimension of the mandible was reduced by the lack of miR­21 (P=0.02). In the maxilla, the dimension of the alveolar bone was significant (P=0.02); however, this was not observed in the molars (P=0.36). Based on principal component analysis, no changes in shape for any of the anatomical sites were observed. Dental and skeletal jaw length were calculated and no prognathism was identified. However, the fluctuating asymmetry of the molars in the mandible and the maxilla was reduced in the miR­21 knockout mice by 38 and 27%, respectively. Taken together, the results of the present study revealed that the molars in the mandible and the dimension of the respective alveolar bone were smaller in miR­21 mice compared with wild­type littermates, suggesting that miR­21 influences tooth development.