Bio-orthogonal Glycan Imaging of Culture Cells and Whole Animal C. elegans with Expansion Microscopy.

Complex carbohydrates called glycans play crucial roles in the regulation of cell and tissue physiology, but how glycans map to nanoscale anatomical features must still be resolved. Here, we present the first nanoscale map of mucin-type O -glycans throughout the entirety of the Caenorhabditis elegans model organism. We construct a library of multifunctional linkers to probe and anchor metabolically labelled glycans in expansion microscopy (ExM), an imaging modality that overcomes the diffraction limit of conventional optical microscopes through the physical expansion of samples embedded in a polyelectrolyte gel matrix. A flexible strategy is demonstrated for the chemical synthesis of linkers with a broad inventory of bio-orthogonal functional groups, fluorophores, anchorage chemistries, and linker arms. Employing C. elegans as a test bed, we resolve metabolically labelled O -glycans on the gut microvilli and other nanoscale anatomical features using our ExM reagents and optimized protocols. We use transmission electron microscopy images of C. elegans nano-anatomy as ground truth data to validate the fidelity and isotropy of gel expansion. We construct whole organism maps of C. elegans O -glycosylation in the first larval stage and identify O -glycan "hotspots" in unexpected anatomical locations, including the body wall furrows. Beyond C. elegans , we provide validated ExM protocols for nanoscale imaging of metabolically labelled glycans on cultured mammalian cells. Together, our results suggest the broad applicability of the multifunctional reagents for imaging glycans and other metabolically labelled biomolecules at enhanced resolutions with ExM.

Collaboration and growth in a large research cooperative: A network analytic approach.

Research networks encourage team science and facilitate collaboration within and across research teams. While many analyses have examined the output of these collaborative networks (e.g., authorship networks, publications, grant applications), less attention has been paid to the formative phases of these initiatives. This article presents analyses of a whole-network survey of investigators participating in a new research initiative, and examines the development of collaborative ties over the network's first year. In particular, we examine the influence of research center affiliation, seniority, and prior network experience on the number and structure of collaborative ties, including participants' bridging and broker roles. Such analyses can inform the overall management of the project in purposefully promoting new collaboration opportunities, and may ultimately predict the number of collaborative products generated by the network members.

Beyond scale-free networks: integrating multilayer social networks with molecular clusters in the local spread of COVID-19.

This study evaluates the scale-free network assumption commonly used in COVID-19 epidemiology, using empirical social network data from SARS-CoV-2 Delta variant molecular local clusters in Houston, Texas. We constructed genome-informed social networks from contact and co-residence data, tested them for scale-free power-law distributions that imply highly connected hubs, and compared them to alternative models (exponential, log-normal, power-law with exponential cutoff, and Weibull) that suggest more evenly distributed network connections. Although the power-law model failed the goodness of fit test, after incorporating social network ties, the power-law model was at least as good as, if not better than, the alternatives, implying the presence of both hub and non-hub mechanisms in local SARS-CoV-2 transmission. These findings enhance our understanding of the complex social interactions that drive SARS-CoV-2 transmission, thereby informing more effective public health interventions.

Prevalence, Incidence, and Predictors of Kaposi Sarcoma-associated Herpesvirus Infection Among Young Men Who Have Sex with Men in the Southern United States.

Kaposi Sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern US. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for Kaposi Sarcoma-associated herpesvirus (KSHV) IgG. Measuring seroprevalence, seroconversion between timepoints, and demographic and clinical correlates, KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS diagnosis and outcomes.

Are human papillomavirus knowledge and vaccine uptake associated with HIV status and social determinants of health in young sexual minority men?

This brief report examines the relationship, if any, between human immunodeficiency virus (HIV) status, and individual-level and socio-sexual partner-level factors of social determinants of health (SDOH) that are associated with human papillomavirus (HPV) knowledge and vaccine uptake in young sexual minority men (YSMM). We used data from 126 YSMM recruited by network-based sampling during 2015-2016 in Houston, Texas. Descriptive statistics and regression analyses were conducted to test the association between HIV status, SDOH, and HPV knowledge and vaccine uptake. Those living with HIV had lower odds of knowledge of HPV-associated anal cancer (OR: 0.43, 95% CI: 0.18-0.97) and knowledge of HPV spreading via sexual contact (OR: 0.11, 95% CI: 0.01-0.64), and higher odds of HPV vaccine uptake (OR: 2.90, 95% CI: 1.11-8.02). HPV knowledge and vaccine uptake in YSMM was not associated with partner's attributes or individuals' SDOH factors in our study yet was significantly associated with HIV status. Future interventions are needed to increase HPV knowledge among individuals living with HIV and vaccine uptake particularly among YSMM living without HIV that are not engaged in healthcare.

Social networks, high-risk anal HPV and coinfection with HIV in young sexual minority men.

OBJECTIVES: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV. The study also examined whether socially connected men are infected with the same high-risk HPV genotypes and, if so, whether this tendency is conditioned on coinfection with HIV. METHODS: Our sample included 136 young SMM of predominantly black race and their network members of other races and ethnicities, aged 18-29 years, who resided in Houston, Texas, USA. These participants were recruited during 2014-2016 at the baseline recruitment period by network-based peer referral, where anal exfoliated cells and named social and sexual partners were collected. Exponential random graph models were estimated to assess similarity in genotype-specific hrHPV anal infection in social connections and coinfection with HIV in consideration of the effects of similarity in sociodemographic, sexual behavioural characteristics, SDOHs and syphilis infection. RESULTS: Pairs of men socially connected to each other tend to be infected with the same hrHPV genotypes of HPV-16, HPV-45 and HPV-51 or HPV-16 and/or HPV-18. The tendency of social connections between pairs of men who were infected with either HPV-16 or HPV-18 were conditioned on HIV infection. CONCLUSIONS: Networked patterns of hrHPV infection could be amenable to network-based HPV prevention interventions that engage young SMM of predominantly racial minority groups who are out of HIV care and vulnerable to high-risk HPV acquisition.

A new statistical model for longitudinal ecological momentary assessment data on dual use of electronic and combustible cigarettes.

Background: Existing studies of dual use of electronic and combustible cigarettes either collected longitudinal data with long gaps in between waves or conducted ecological momentary assessment (EMA) over a short period of time. In recent years, the measurement burst design that embeds an EMA protocol in each wave assessment of a traditional longitudinal study has become more popular and yet conventional generalized linear mixed models (GLMM) have important limitations for handling data from this design.Objectives: This study proposed a new statistical method to analyze data from the measurement burst design.Methods: This new statistical method was designed to model the short-term (within-wave) as well as long-term (between-wave) changes and was validated by a simulation study. Secondary analysis was conducted to analyze data from 205 dual users (52% male) and 146 exclusive smokers (50% male) who participated in a recent study using the measurement burst design.Results: The simulation study shows that the proposed method can handle the gap between waves well and is also robust to nonlinear changes across waves. Although no short-term change in smoking was found, dual users reported a long-term reduction in cigarette use that was more rapid compared to exclusive smokers (߈=-0.0127,p=.0167). Vaping more was associated with smoking less (߈=-0.0058,p=.0054).Conclusion: The proposed method is highly applicable as it can be easily implemented by substance use researchers and the results can be straightforwardly interpreted. The results suggest that e-cigarette use may play a role in promoting a long-term reduction in smoking among dual users.

Integrated molecular and affiliation network analysis: Core-periphery social clustering is associated with HIV transmission patterns.

This study investigates the two-mode core-periphery structures of venue affiliation networks of younger Black men who have sex with men (YBMSM). We examined the association between these structures and HIV phylogenetic clusters, defined as members who share highly similar HIV strains that are regarded as a proxy for sexual affiliation networks. Using data from 114 YBMSM who are living with HIV in two large U.S. cities, we found that HIV phylogenetic clustering patterns were associated with social clustering patterns whose members share affiliation with core venues that overlap with those of YBMSM. Distinct HIV transmission patterns were found in each city, a finding that can help to inform tailored venue-based and network intervention strategies.

Determining Risk Factors That Affect Progression in Patients with Nonproliferative Diabetic Retinopathy.

PURPOSE: To determine risk factors that affect nonproliferative diabetic retinopathy (NPDR) progression and establish a predictive model to estimate the probability of and time to progression in NPDR. Patients and Methods. Charts of diabetic patients who received an initial eye exam between 2010 and 2017 at our county hospital were included. Patients with proliferative diabetic retinopathy (PDR), fewer than 2 years of follow-up, or fewer than 3 clinic visits were excluded. Demographics and baseline systemic and ocular characteristics were recorded. Follow-up mean annual HbA1c and blood pressure, best-corrected visual acuity, and the number of antivascular endothelial growth factor treatments were recorded. Stage and date of progression were recorded. A 5-state nonhomogeneous continuous-time Markov chain with a backward elimination model was used to identify risk factors and estimate their effects on progression. RESULTS: Two hundred thirty patients were included. Initially, 65 eyes (28.3%) had no retinopathy; 73 (31.7%) mild NPDR; 60 (26.1%) moderate NPDR; and 32 (13.9%) severe NPDR. Patients were followed for a mean of 5.8 years (±2.0 years; range 2.1-9.4 years). 164 (71.3%) eyes progressed during the follow-up. Time-independent risk factors affecting progression rate were age (hazard ratio (HR) = 0.99, P=0.047), duration of diabetes (HR = 1.02, P=0.018), and Hispanic ethnicity (HR = 1.31, P=0.068). Mean sojourn times at mean age, duration of diabetes, and annual HbA1c for a non-Hispanic patient were estimated to be 3.03 (±0.97), 4.63 (±1.21), 6.18 (±1.45), and 4.85 (±1.25) years for no retinopathy, mild NPDR, moderate NPDR, and severe NPDR, respectively. Each 1% increase in HbA1c annually diminished sojourn times by 15%, 10%, 7%, and 10% for no retinopathy, mild NPDR, moderate NPDR, and severe NPDR, respectively. CONCLUSION: HbA1c level is a significant modifiable risk factor in controlling the progression of DR. The proposed model could be used to predict the time and rate of progression based on an individual's risk factors. A prospective multicenter study should be conducted to further validate our model.