Determinants of Willingness to Use PrEP Among Gay and Bisexual Men in China Before Implementation: A Structural Equation Modeling Assessment.

With the recent endorsement of PrEP by the Chinese government, research is urgently needed to better understand factors impacting PrEP uptake among gay, bisexual, and other men who have sex with men (GBMSM) in China. This study examined willingness to use PrEP for HIV prevention among GBMSM in China through structural equation modeling. We examined the relationship among PrEP-related attitudes, subjective norms, PrEP-related knowledge and beliefs about medicines and willingness to use PrEP. The analysis showed a good fit between the data and both the measurement model (RMSEA = 0.060) and structural model (RMSEA = 0.054). Knowledge, attitudes, and subjective norms were significantly related to intention to use PrEP, whereas the effect of general beliefs about medicines was insignificant. These effect mechanisms point to the importance of designing interventions to support PrEP uptake that target knowledge, enhance positive attitudes about PrEP within social networks, and build positive social norms around PrEP among sexually active GBMSM.

Single-Cell Transcriptome Identifies the Renal Cell Type Tropism of Human BK Polyomavirus.

BK polyomavirus (BKPyV) infection is the main factor affecting the prognosis of kidney transplant recipients, as no antiviral agent is yet available. A better understanding of the renal-cell-type tropism of BKPyV can serve to develop new treatment strategies. In this study, the single-cell transcriptomic analysis demonstrated that the ranking of BKPyV tropism for the kidney was proximal tubule cells (PT), collecting duct cells (CD), and glomerular endothelial cells (GEC) according to the signature of renal cell type and immune microenvironment. In normal kidneys, we found that BKPyV infection-related transcription factors P65 and CEBPB were PT-specific transcription factors, and PT showed higher glycolysis/gluconeogenesis activities than CD and GEC. Furthermore, in the BKPyV-infected kidneys, the percentage of late viral transcripts in PT was significantly higher than in CD and GEC. In addition, PT had the smallest cell-cell interactions with immune cells compared to CD and GEC in both normal and BKPyV-infected kidneys. Subsequently, we indirectly demonstrated the ranking of BKPyV tropism via the clinical observation of sequential biopsies. Together, our results provided in-depth insights into the renal cell-type tropism of BKPyV in vivo at single-cell resolution and proposed a novel antiviral target.

Community engagement on-site rapid test for chlamydia and gonorrhea among men who have sex with men: a pioneering study in Guangzhou, China.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO). METHOD: We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment. RESULTS: From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was "free for charge" (66.2%), followed by "convenient, 'shorter waiting time" (45.2%) and "had high-risk sexual behavior recently" (16.3%). CONCLUSIONS: This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.

Upregulated FKBP1A Suppresses Glioblastoma Cell Growth via Apoptosis Pathway.

Glioblastoma (GBM), the most deadly primary brain tumor, presents a major medical difficulty. The need for better therapeutic targets in GBM is therefore urgent. A growing body of evidence suggests that the gene FKBP1A plays an important role in tumor progression and may be therapeutically useful. However, the role of FKBP1A in glioblastoma and the underlying biologic mechanism remain unclear. The purpose of this study was to identify the role of FKBP1A in GBM and its molecular mechanism. We demonstrated that FKBP1A was the hub gene in GBM via a weighted correlation network analysis (WGCNA) and differentially expressed genes (DEGs) analysis based on the bulk RNA-seq data from TCGA and GTEx. Afterwards, we proved that the upregulated FKBP1A protein could promote GBM cell death by CCK-8 assays in U87MG and t98g GBM cell lines. We further demonstrated two key pathways of FKBP1A in GBM by bioinformatics methods: 'Apoptosis' and 'mTOR signaling pathway'. Subsequently, the key pathways were verified by flow cytometry and Western blot. We identified that upregulated FKBP1A could inhibit GBM growth via the apoptosis pathway. Together, these findings may contribute to future GBM treatment.

Post-exposure prophylaxis: an underutilized biomedical HIV prevention method among gay, bisexual and other men who have sex with men in China.

Despite abundant evidence on its safety, tolerability and cost-effectiveness, post-exposure prophylaxis (PEP) has not been officially approved for non-occupational use in China. This study aims to assess awareness of, willingness to use, and actual experience with PEP in gay, bisexual and other men who have sex with men (GBM) in China and to explore potential associations between demographic, behavioral, and psychosocial factors and PEP-related outcomes. We recruited a convenience sample through community venue-based strategies, peer referrals, and online advertisement in four cities of China in 2018. We used bivariable and multivariable logistic regression to test associations between potential predictors and PEP outcomes. Over 60% of men reported having heard of PEP prior to the survey, 70% would be willing to use it if exposed to HIV, and 6% reported having used PEP. Awareness of PEP was associated with higher education, more frequent HIV testing, knowing someone who seroconverted in the past two years, having sex with only men in the past six months, and lower perceived risk of HIV infection. PEP willingness was associated with more frequent HIV testing, being worried about becoming HIV infected, prior awareness and favorable attitudes towards PEP among friends. Findings suggest PEP is an underutilized diomedical HIV prevention intervention among GBM in China. Clinical guidance on non-occupational PEP use, as well as communication campaigns targeting social networks of GBM are needed to address barriers to PEP awareness and uptake.

Do gay and bisexual men who conceal their same-sex behavior prefer different kinds of health services? Findings across four cities to inform client-centered HIV prevention in China.

BACKGROUND: In China, addressing disparities in the HIV epidemic among men who have sex with men (MSM) requires targeted efforts to increase their engagement and retention in prevention. In an effort to advance MSM-friendly HIV services within China, and informed by community-based partnerships, we tested whether MSM who have ever versus never disclosed their same-sex behavior to healthcare providers (HCP) differ in sociodemographic and behavioral characteristics as well as the qualities of sexual health services each group would prefer to access. METHODS: We conducted a cross-sectional survey among HIV-negative MSM who went to MSM-focused voluntary counseling and testing clinics in four cities in China. The survey was anonymous and collected information on sociodemographic characteristics, testing behaviors, sexual-health related behavior, and sexual health service model preferences. RESULTS: Of 357 respondents, 68.1% participants had ever disclosed same-sex behavior to HCPs when seeking advice for sexual health. Younger age (aOR = 1.04; 95% CI: 1.01-1.08), and worry of HIV acquisition (aOR = 1.39; 95% CI: 1.05-1.84) were associated with higher odds of past disclosure. The availability of comprehensive sexual health services was one of the most valued characteristics of the ideal sexual health clinic. Those who ever disclosed and never disclosed differed significantly in their ranking of the importance of three out of ten dimensions: sexual health counseling services available (M = 3.99 vs. M = 3.65, p = .002), gay identity support available (M = 3.91 vs. M = 3.62, p = .016) and clinic collaborates with a gay CBO (M = 3.81 vs. M = 3.56, p = .036). CONCLUSIONS: Our hypothesis that MSM who had disclosed versus never disclosed same-sex behavior would differ in the value they placed on different dimensions of sexual health service was partially borne out. As health authorities in China decide on implementation models for pre-exposure prophylaxis (PrEP) delivery and specifically within which institutions to integrate PrEP services, the preferences of target populations should be considered to develop comprehensive, patient-centric and LGBT-friendly services.

Risk Behavior Not Associated with Self-Perception of PrEP Candidacy: Implications for Designing PrEP Services.

In a study of sexually-active HIV-negative men who have sex with men (MSM) in China, we compared behavioral indication for pre-exposure prophylaxis (PrEP) based on risk criteria to self-perception of PrEP candidacy (SPC) and explored factors associated with SPC. Of 708 MSM surveyed, 323 (45.6%) were behaviorally-indicated for PrEP, among whom 42.1% self-perceived as appropriate PrEP candidates. In a multivariable model we found no association between sexual behavior nor HIV risk perception and SPC but found that higher perceived benefits of PrEP, increased frequency of HIV testing, and low condom use self-efficacy were positively-associated with SPC. In a sub-analysis restricted to MSM behaviorally-indicated for PrEP, relationship-factors were also significant. Our findings suggest that PrEP implementers should look beyond risk criteria to consider shared decision-making tools that support individuals to assess whether they are appropriate PrEP candidates based on their existing HIV prevention strategies, sexual health goals, and relationship dynamics.

An Incognito Standardized Patient Approach for Measuring and Reducing Intersectional Healthcare Stigma.

Background: Consistent evidence highlights the role of stigma in impairing healthcare access in people living with HIV (PLWH), men who have sex with men (MSM), and people with both identities. We developed an incognito standardized patient (SP) approach to obtain observations of providers to inform a tailored, relevant, and culturally appropriate stigma reduction training. Our pilot cluster randomized control trial assessed the feasibility, acceptability, and preliminary effects of an intervention to reduce HIV stigma, anti-gay stigma, and intersectional stigma. Methods: Design of the intervention was informed by the results of a baseline round of incognito visits in which SPs presented standardized cases to consenting doctors. The HIV status and sexual orientation of each case was randomly varied, and stigma was quantified as differences in care across scenarios. Care quality was measured in terms of diagnostic testing, diagnostic effort, and patient-centered care. Impact of the training, which consisted of didactic, experiential, and discussion-based modules, was assessed by analyzing results of a follow-up round of SP visits using linear fixed effects regression models. Results: Feasibility and acceptability among the 55 provider participants was high. We had a 87.3% recruitment rate and 74.5% completion rate of planned visits (N=238) with no adverse events. Every participant found the training content "highly useful" or "useful." Preliminary effects suggest that, relative to the referent case (HIV negative straight man), the intervention positively impacted testing for HIV negative MSM (0.05 percentage points [PP], 95% CI,-0.24, 0.33) and diagnostic effort in HIV positive MSM (0.23 standard deviation [SD] improvement, 95% CI, -0.92, 1.37). Patient-centered care only improved for HIV positive straight cases post-training relative to the referent group (SD, 0.57; 95% CI, -0.39, 1.53). All estimates lacked statistical precision, an expected outcome of a pilot RCT. Conclusions: Our pilot RCT demonstrated high feasibility, acceptability, and several areas of impact for an intervention to reduce enacted healthcare stigma in a low-/middle-income country setting. The relatively lower impact of our intervention on care outcomes for PLWH suggests that future trainings should include more clinical content to boost provider confidence in the safe and respectful management of patients with HIV.

Young LINE-1 transposon 5' UTRs marked by elongation factor ELL3 function as enhancers to regulate naïve pluripotency in embryonic stem cells.

LINE-1s are the major clade of retrotransposons with autonomous retrotransposition activity. Despite the potential genotoxicity, LINE-1s are highly activated in early embryos. Here we show that a subset of young LINE-1s, L1Md_Ts, are marked by the RNA polymerase II elongation factor ELL3, and function as enhancers in mouse embryonic stem cells. ELL3 depletion dislodges the DNA hydroxymethylase TET1 and the co-repressor SIN3A from L1Md_Ts, but increases the enrichment of the Bromodomain protein BRD4, leading to loss of 5hmC, gain of H3K27ac, and upregulation of the L1Md_T nearby genes. Specifically, ELL3 occupies and represses the L1Md_T-based enhancer located within Akt3, which encodes a key regulator of AKT pathway. ELL3 is required for proper ERK activation and efficient shutdown of naïve pluripotency through inhibiting Akt3 during naïve-primed transition. Our study reveals that the enhancer function of a subset of young LINE-1s controlled by ELL3 in transcription regulation and mouse early embryo development.

ZFP281-BRCA2 prevents R-loop accumulation during DNA replication.

R-loops are prevalent in mammalian genomes and involved in many fundamental cellular processes. Depletion of BRCA2 leads to aberrant R-loop accumulation, contributing to genome instability. Here, we show that ZFP281 cooperates with BRCA2 in preventing R-loop accumulation to facilitate DNA replication in embryonic stem cells. ZFP281 depletion reduces PCNA levels on chromatin and impairs DNA replication. Mechanistically, we demonstrate that ZFP281 can interact with BRCA2, and that BRCA2 is enriched at G/C-rich promoters and requires both ZFP281 and PRC2 for its proper recruitment to the bivalent chromatin at the genome-wide scale. Furthermore, depletion of ZFP281 or BRCA2 leads to accumulation of R-loops over the bivalent regions, and compromises activation of the developmental genes by retinoic acid during stem cell differentiation. In summary, our results reveal that ZFP281 recruits BRCA2 to the bivalent chromatin regions to ensure proper progression of DNA replication through preventing persistent R-loops.

Posttraumatic Stress Disorder and Nonadherence to Treatment in People Living With HIV: A Systematic Review and Meta-analysis.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a commonly reported and serious complication among people living with HIV (PLWH). PTSD may significantly increase unintentional non-adherence to antiretroviral therapy. In this systematic review and meta-analysis, we aimed to pool the observational studies exploring the association between PTSD and medication adherence among PLWH. METHODS: Comprehensive searches were conducted in PubMed/Medline, Web of Science, PsycINFO, Google Scholar, and ProQuest to identify relevant articles and dissertations. A random effects meta-analysis with inverse variance weighting was used to summarize the odds ratio (OR) across studies. Meta-regression and subgroup analyses were also carried out to assess the moderation effects for potential factors. RESULTS: By synthesizing 12 studies comprising 2489 participants, the pooled odd ratio of non-adherence to antiretroviral therapy was 1.19 (95% confidential interval (CI), 1.03-1.37, p = 0.02). No significant publication bias was detected by Egger's test (Intercept = 0.842, p = 0.284). Factors moderating the association were mean age of participants, depression adjustment, and depression (all p < 0.05). CONCLUSIONS: This meta-analysis supports that PTSD is related to adherence in PLWH. The hypothesized mechanisms (avoidant behavior and cognitive impairment) underlying this association need further investigation. Overall, this study highlights that clinicians should thoughtfully integrate timely mental health intervention into routine care.

RNF219 interacts with CCR4-NOT in regulating stem cell differentiation.

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING finger protein 219 (RNF219) interacts with the CCR4-NOT deadenylase complex. RNF219-CCR4-NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown, while upregulated after depletion of the CCR4-NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT and required for maintenance of ES cell pluripotency.

Mapping Potential Pre-Exposure Prophylaxis Users onto a Motivational Cascade: Identifying Targets to Prepare for Implementation in China.

Purpose: China recently commenced several pre-exposure prophylaxis (PrEP) projects, but little work has characterized potential users. This study describes awareness of, intention to use, and uptake of PrEP in a sample of men who have sex with men (MSM), a key population experiencing high rates of HIV in China. Methods: Through a cross-sectional survey administered to 708 MSM in four cities, we mapped respondents onto a Motivational PrEP Cascade. We conducted bivariable and multivariable analysis to examine factors associated with progression through the Cascade. Results: Among 45.6% of MSM who were PrEP eligible, 36% were in Contemplation, 9% were in PrEParation, 2% were in PrEP Action and Initiation, and none reached Maintenance and Adherence. We found no association between individual risk factors and progression through the Cascade. In multivariable analysis, friends' positive attitudes toward PrEP, more frequent sexually transmitted infection testing, and higher scores on the perceived PrEP benefits scale were positively associated with entering PrEP Contemplation. Having higher condom use self-efficacy was associated with decreased odds of entering PrEP Contemplation. Having sex with men and women in the past 6 months, having heard of PrEP from medical providers, and knowing a PrEP user were positively associated with entering PrEParation. Conclusion: We found a high proportion of MSM who were PrEP eligible and identified several intervention targets to prepare for PrEP introduction in China: community education to increase accurate knowledge, gain-framed messaging for PrEP and sexual health, and provider trainings to build MSM-competent services that can support shared decision-making for PrEP initiation.

HIV self-testing among men who have sex with men in China: a qualitative implementation research study.

BACKGROUND: HIV self-testing (HIVST) may expand HIV testing, but there have been few pilot programmes among men who have sex with men (MSM). This purpose of this study was to evaluate HIVST implementation among MSM in China using qualitative methods. METHODS: We undertook semistructured interviews among MSM and those organising HIVST programmes for MSM. Purposive sampling method was used to ensure men with different HIV serostatuses, ages and HIVST frequencies were included. Men were recruited from MSM community-based organisations and a local HIV clinic. An implementation science framework was used to interpret the findings. Two individuals used a standard code-based methodology to identify themes. RESULTS: Forty-two MSM and six stakeholders were interviewed. Our data showed many MSM and stakeholders preferred HIVST to facility-based testing. Most men reported that HIVST empowered MSM and informed sexual decision making. Many men noted that decreasing the HIVST price may increase demand. Some men noted that HIVST could be scaled up through social media and by modifying bulky packaging. Minimal adverse events were reported. CONCLUSIONS: HIVST may expand HIV testing and promote empowerment of MSM. Minimal adverse outcomes were noted, but further implementation research is needed.