Improving TDOA Radar Performance in Jammed Areas through Neural Network-Based Signal Processing.

This paper presents a method for estimating the position of a target under jammed conditions using the Time Difference of Arrival (TDOA) method. The algorithm utilizes a deep neural network to overcome the challenges posed by the jammed conditions. The simulations and results indicate that the presented method is more accurate and efficient than the traditional TDOA methods.

Challenges in translational machine learning.

Machine learning (ML) algorithms are increasingly being used to help implement clinical decision support systems. In this new field, we define as "translational machine learning", joint efforts and strong communication between data scientists and clinicians help to span the gap between ML and its adoption in the clinic. These collaborations also improve interpretability and trust in translational ML methods and ultimately aim to result in generalizable and reproducible models. To help clinicians and bioinformaticians refine their translational ML pipelines, we review the steps from model building to the use of ML in the clinic. We discuss experimental setup, computational analysis, interpretability and reproducibility, and emphasize the challenges involved. We highly advise collaboration and data sharing between consortia and institutes to build multi-centric cohorts that facilitate ML methodologies that generalize across centers. In the end, we hope that this review provides a way to streamline translational ML and helps to tackle the challenges that come with it.

The Impact of Advertisement Messaging on Enrollment of Young Men Who Have Sex With Men for Web-Based Research: Observational Study.

BACKGROUND: Recruiting young men who have sex with men (YMSM) in community settings is difficult. The use of Web-based social networks and dating apps for recruitment can be successful approaches, although little work has been done on the impact of study advertisement content on recruitment. OBJECTIVE: The aim of this study was to evaluate the effects of advertisement message content on the recruitment of YMSM (aged 18-26 years) for a Web-based focus group study, examining perspectives and preferences for a mobile app that was designed to support sexual health among YMSM. METHODS: Between March and April 2017, a recruitment campaign to promote human papillomavirus vaccination was launched on a popular social networking and dating app for YMSM, with 3 different text-based advertisement themes (technology, cancer prevention, and sexual innuendo). The campaign recruited YMSM across 3 states (Massachusetts, New York, and Pennsylvania). We examined the click-through rates, conversion rates, and enrollment rates of each of the advertisements and examined differences in views and clicks by age, state, and time of day. RESULTS: The sexual innuendo advertisement had the highest click rates when compared with both the technology (click rate ratio [CRR] 2.06, 95% CI 1.74-2.45) and cancer prevention (CRR 1.62, 95% CI 1.38-1.90) advertisements. The sexual innuendo advertisement also had higher study enrollment rates compared with the technology (CRR 1.90, 95% CI 1.23-2.83) and cancer prevention (CRR 2.06, 95% CI 1.37-3.13) advertisements. No differences were observed in clicks or enrollment by age, state, or time of day. CONCLUSIONS: Our marketing campaign, targeting YMSM, was effective in recruiting participants for a qualitative study, using Web-based focus groups. The sexual innuendo advertisement was the most effective and cost-efficient advertisement of the 3 approaches trialed. Different populations need different targeted strategies for study recruitment. Researchers should work with key representatives to develop and test culturally relevant messaging and approaches that utilize current and popular technologies.

Interaction Patterns of Men Who Have Sex With Men on a Geosocial Networking Mobile App in Seven United States Metropolitan Areas: Observational Study.

BACKGROUND: The structure of the sexual networks and partnership characteristics of young black men who have sex with men (MSM) may be contributing to their high risk of contracting HIV in the United States. Assortative mixing, which refers to the tendency of individuals to have partners from one's own group, has been proposed as a potential explanation for disparities. OBJECTIVE: The objective of this study was to identify the age- and race-related search patterns of users of a diverse geosocial networking mobile app in seven metropolitan areas in the United States to understand the disparities in sexually transmitted infection and HIV risk in MSM communities. METHODS: Data were collected on user behavior between November 2015 and May 2016. Data pertaining to behavior on the app were collected for men who had searched for partners with at least one search parameter narrowed from defaults or used the app to send at least one private chat message and used the app at least once during the study period. Newman assortativity coefficient (R) was calculated from the study data to understand assortativity patterns of men by race. Pearson correlation coefficient was used to assess assortativity patterns by age. Heat maps were used to visualize the relationship between searcher's and candidate's characteristics by age band, race, or age band and race. RESULTS: From November 2015 through May 2016, there were 2,989,737 searches in all seven metropolitan areas among 122,417 searchers. Assortativity by age was important for looking at the profiles of candidates with correlation coefficients ranging from 0.284 (Birmingham) to 0.523 (San Francisco). Men tended to look at the profiles of candidates that matched their race in a highly assortative manner with R ranging from 0.310 (Birmingham) to 0.566 (Los Angeles). For the initiation of chats, race appeared to be slightly assortative for some groups with R ranging from 0.023 (Birmingham) to 0.305 (Los Angeles). Asian searchers were most assortative in initiating chats with Asian candidates in Boston, Los Angeles, New York, and San Francisco. In Birmingham and Tampa, searchers from all races tended to initiate chats with black candidates. CONCLUSIONS: Our results indicate that the age preferences of MSM are relatively consistent across cities, that is, younger MSM are more likely to be chatted with and have their profiles viewed compared with older MSM, but the patterns of racial mixing are more variable. Although some generalizations can be made regarding Web-based behaviors across all cities, city-specific usage patterns and trends should be analyzed to create targeted and localized interventions that may make the most difference in the lives of MSM in these areas.

Electrocatalytic artificial carbonylation assay for observation of human serum albumin inter-individual properties.

Human serum albumin (HSA) is a multifunctional protein with ligand binding, transporting and buffering properties. Posttranslational modifications and ligand binding processes are closely related to albumin final functional status. In the last few decades, HSA has been characterized using a broad spectrum of methods, but quantitative data on the HSA's modifications among individuals have not been reported. The investigations presented here are based on the non-denaturing electrocatalytic screening of HSA samples isolated from the blood serum of healthy subjects. The electrocatalytic responses of the native protein (Rnat) varied depending on its modifications among individuals, which enable us to express the inter-individual variability. Consequently, the native HSA samples were subjected to ex vivo carbonylation with 50 mM methylglyoxal for 36 h. The differences between Rnat and the responses of artificially carbonylated protein (Rmod) corresponded with inter-individual binding capacity variations (ΔR = Rnat-Rmod). The coefficients of variation for the Rnat and ΔR values of purified HSA samples were estimated to be 8.5 and 23.2%, respectively. A sensitive non-denaturing electrocatalytic assay was utilized to provide new data about albumin inter-individual variations and evaluate its oxidative modifications and binding capacity, which could be used for further studies targeting not only on HSA but also other clinically important proteins.

Structural Stability of Peptidic His-Containing Proton Wire in Solution and in the Adsorbed State.

Molecular wires are functional molecules applicable in the field of transfer processes in technological and biochemical applications. Besides molecular wires with the ability to transfer electrons, research is currently focused on molecular wires with high proton affinity and proton transfer ability. Recently, proposed peptidic proton wires (H wires) are one example. Their ability to mediate the transport of protons from aqueous solutions onto the surface of a Hg electrode in a catalytic hydrogen evolution reaction was investigated by constant-current chronopotentiometric stripping. However, elucidating the structure of H wires and rationalizing their stability are key requirements for their further research and application. In this article, we focus on the His (H) and Ala (A)-containing peptidic H wire A3-(H-A2)6 in solution and after its immobilization onto the electrode surface in the presence of the secondary structure stabilizer 2,2,2-trifluoroethanol (TFE). We found that the solvent containing more than 25% of TFE stabilizes the helical structure of A3-(H-A2)6 not only in solution but also in the adsorbed state. The TFE efficacy to stabilize α-helical structure was confirmed using high-resolution nuclear magnetic resonance, circular dichroism, and molecular dynamics simulation. Experimental and theoretical results indicated A3-(H-A2)6 to be a high proton-affinity peptidic H wire with an α-helical structure stabilized by TFE, which was confirmed in a comparative study with hexahistidine as an example of a peptide with a definitely disordered and random coil structure. The results presented here could be used for further investigation of the peptidic H wires and for the application of electrochemical methods in the research of proton transfer phenomena in general.

MSM at Highest Risk for HIV Acquisition Express Greatest Interest and Preference for Injectable Antiretroviral PrEP Compared to Daily, Oral Medication.

Men who have sex with men (MSM) account for nearly 70% of new HIV diagnoses, with young black MSM at the highest risk for infection in the United States. Pre-exposure prophylaxis (PrEP) can decrease HIV acquisition in at-risk individuals by over 90%. However, therapeutic efficacy requires a daily pill, posing adherence challenges. Experimental modalities, including injectable PrEP given once every 2 months, may improve adherence among those most in need. To assess interest in and preference for injectable PrEP, an online survey was mounted on two popular MSM sexual networking apps. Differences by age, race, and other characteristics were examined using multinomial logistic regressions. Of 4638 respondents, 73% expressed interest in injectable PrEP and 47% indicated they would prefer an injection (compared to 17% who prefer a daily pill and 36% who were unsure). Within this sample, interest in and preference for injectable PrEP was highest among MSM at highest risk for HIV infection (i.e., younger age groups, racial/ethnic minorities, those with risker sexual behavior). As a result, if proven effective in clinical trials, injectable PrEP has the potential to reduce social disparities in HIV transmission among MSM.

The impact of social support and partner relationship dynamics on engagement in HIV care and antiretroviral treatment adherence among MSM in Latin America.

In Latin America (LA), HIV prevalence among MSM is estimated at thirty times greater than in the general male population. Little is known about the role of social support or disclosure status in relation to the HIV care continuum among LA MSM. Using multivariable logistic generalized estimation equations, we assessed the impact of social support satisfaction and disclosure status on engagement in HIV care, ART initiation, and ART adherence with data from an online, multinational sample of HIV infected MSM in Latin America (N = 2,350). 80.0% were engaged in HIV care, 71% initiated ART, and among those, 37% reported missing at least one dose in the past month. In multivariable models, compared to being very satisfied with social support, being somewhat satisfied (aOR = 0.73, 95% CI 0.56, 0.95) or somewhat dissatisfied (aOR = 0.83, 95% CI 0.70, 0.98) were associated with reduced odds of reporting 100% ART adherence. Disclosure of status was associated with a greater odds of HIV care engagement (OR = 1.63, 95% CI 1.28, 2.07) and ART initiation (OR = 1.55, 95% CI 1.30, 1.84). Greater satisfaction with social support and comfort disclosing HIV status to these sources were associated with improved engagement in HIV care and greater initiation of ART among MSM in LA.

Early Adopters: Correlates of HIV Chemoprophylaxis Use in Recent Online Samples of US Men Who Have Sex with Men.

To date, little data on pre-exposure prophylaxis (PrEP) users outside of the clinical trial setting are available. A repeated cross-sectional survey of one of the largest social and sexual networking websites for men who have sex with men (MSM) in the United States was conducted in August 2013 (Wave 1) and January 2014 (Wave 2). Multivariable logistic regression models were used to assess factors associated with having heard of and having taken post-exposure prophylaxis (PEP) and PrEP in Wave 1 (N = 4043) and Wave 2 (N = 2737) separately. In Wave 1, 147 (3.6 %) and 61 (1.5 %) reported using PEP and PrEP, respectively, compared to 119 (4.4 %) and 62 (2.3 %) in Wave 2. Higher-risk sexual behaviors were associated with having taken PEP and PrEP, and previous PEP use was associated with having taken PrEP. Understanding factors that are associated with early use of PrEP may help inform wider utilization of PrEP by at risk MSM.

Seasons of Risk: Anticipated Behavior on Vacation and Interest in Episodic Antiretroviral Pre-exposure Prophylaxis (PrEP) Among a Large National Sample of U.S. Men Who have Sex with Men (MSM).

The current analysis evaluates interest in and acceptability of daily PrEP during short episodes of anticipated increased risk (i.e. Epi-PrEP). In 2013, U.S. members of an internet-based MSM sexual networking site were invited to complete a survey about HIV prevention practices in the context of vacationing. 7305 MSM responded to the survey. Of respondents who had vacationed in the past year, 25.6 % reported condomless anal sex (CAS) with new male sex partners while vacationing. Most (92.6 %) respondents agreed that having to use PrEP every day was a barrier to PrEP use and 74.3 % indicated they would take PrEP if they knew it would be helpful for short periods of anticipated increased risk. MSM who reported increased CAS while on vacation in the past year were more likely to indicate that they would take PrEP if it were helpful when used for short periods than respondents who did not (aOR = 2.02, 95 % CI 1.59-2.56, p < 0.001). Studies designed to evaluate uptake, adherence, and protective benefit of short PrEP courses are warranted.

Multiple syndemic psychosocial factors are associated with reduced engagement in HIV care among a multinational, online sample of HIV-infected MSM in Latin America.

Latin America has some of the highest levels of antiretroviral therapy (ART) coverage of any developing region in the world. Early initiation and optimal adherence to ART are necessary for improved health outcomes and reduction in onward transmission. Previous work has demonstrated the role of psychosocial problems as barriers to uptake and adherence to ART, and recently, a syndemic framework has been applied to the role of multiple psychosocial syndemic factors and adherence to ART, in the USA. However, to our knowledge, these associations have not been investigated outside of the USA, nor in a multi-country context. To address these gaps, we assessed the association between multiple co-occurring psychosocial factors and engagement in HIV-related medical care and adherence to ART among a large, multinational sample of sexually-active HIV-infected men who have sex with men in Latin America. Among the 2020 respondents, 80.7% reported currently receiving HIV-related medical care, 72.3% reported currently receiving ART; among those, 62.5% reported 100% adherence. Compared with experiencing no psychosocial health problems, experiencing five or more psychosocial health problems is associated with 42% lower odds of currently receiving HIV-related medical care (adjusted odds ratio, aOR = 0.58, 95% CI 0.36, 0.95) and of currently receiving ART (aOR = 0.58, 95% CI 0.38, 0.91). The number of psychosocial health problems experienced was associated with self-reported ART adherence in a dose-response relationship; compared to those with none of the factors, individuals with one syndemic factor had 23% lower odds (aOR = 0.77, 95% CI 0.60, 0.97) and individuals with five or more syndemic factors had 72% lower odds (aOR = 0.28, 95% CI 0.14, 0.55) of reporting being 100% adherent to ART. Addressing co-occurring psychosocial problems as potential barriers to uptake and adherence of ART in Latin America may improve the effectiveness of secondary prevention interventions.

Transactional sex among men who have sex with men in Latin America: economic, sociodemographic, and psychosocial factors.

OBJECTIVES: We assessed factors associated with engagement in transactional sex among men who have sex with men recruited from one of the largest Internet sites for men seeking social or sexual interactions with other men in Latin America. METHODS: We constructed multilevel logistic regression models to analyze factors associated with engagement in transactional sex in 17 Latin American countries in 2012. RESULTS: Of 24 051 respondents, 1732 (7.2%) reported being paid for sexual intercourse in the past 12 months. In a multivariable model, higher country-level unemployment was associated with increased odds of transactional sex (adjusted odds ratio [AOR] = 1.07 per 1% increase in unemployment; 95% confidence interval [CI] = 1.00, 1.13). Individual or interpersonal factors associated with increased odds of engagement in transactional sex included self-reported HIV (AOR = 1.33; 95% CI = 1.04, 1.69) or sexually transmitted infection (AOR = 1.33; 95% CI = 1.11, 1.59), childhood sexual abuse history (AOR = 1.75; 95% CI = 1.48, 2.06), intimate partner violence (past 5 years, AOR = 1.68; 95% CI = 1.45, 1.95), and sexual compulsivity (AOR = 1.77; 95% CI = 1.49, 2.11). CONCLUSIONS: Structural-level economic interventions and those that address individual and interpersonal factors may improve HIV prevention efforts among men who have sex with men who engage in transactional sex.

Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B.

PURPOSE: Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB. MATERIALS AND METHODS: A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168. RESULTS: Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively. CONCLUSION: The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.

Engagement in HIV care and sexual transmission risk behavior among men who have sex with men using online social/sexual networking in Latin America.

HIV/AIDS in Latin America is concentrated among men who have sex with men (MSM). However, accurate estimates of engagement in HIV care in this population can be difficult to ascertain because many do not self-identify as MSM. Given evidence of decreased HIV transmissibility in the context of antiretroviral therapy (ART) adherence, identifying individuals not in care who are engaging in HIV transmission risk behavior is crucial for secondary prevention. Primary aims of this study were to examine engagement in care from testing to ART adherence among MSM using online social/sexual networking across Latin America, and whether individuals not in care at each step reported greater sexual transmission risk behavior than those in care. In the overall sample (n=28,779), approximately 75% reported ever being tested for HIV, and 9% reported having received an HIV diagnosis. Among known HIV-infected individuals, 20% reported not being in care, 30% reported not taking ART, and 55% reported less than 100% ART adherence. Over one-third of HIV-infected individuals reported sexual HIV transmission risk behavior, defined as unprotected anal intercourse (UAI) with a male partner of different/unknown HIV serostatus in the past three months. HIV-infected individuals not engaged in care more often reported UAI compared to those in care (OR=1.29; 95% CI=1.01-1.66). Although not statistically significant, HIV-infected individuals not on ART more often reported UAI compared to those on ART (OR=1.18; 95% CI=0.94-1.47). Individuals who reported less than 100% ART adherence more often reported UAI compared to individuals with 100% adherence (OR=1.55; 95% CI=1.26-1.90). Findings demonstrate that a substantial portion of HIV-infected MSM in Latin America who are likely not virologically suppressed from lack of ART use or adherence report sexual HIV transmission risk. Tailoring secondary HIV prevention for MSM in Latin America who are not in HIV care or adherent to ART may be warranted.

Pleasure, affection, and love among Black men who have sex with men (MSM) versus MSM of other races: countering dehumanizing stereotypes via cross-race comparisons of reported sexual experience at last sexual event.

Black men have historically been stereotyped as hedonistic, aggressive, and animalistic in their sexual interactions. This study sought to describe pleasure, affection, and love experienced by Black men who have sex with men (MSM) during their last male-partnered sexual event and to examine differences relative to White, Latino, and Asian MSM. A total of 21,696 (793 Black, 18,905 White, 1,451 Latino, and 547 Asian) U.S. men ages 18-87 (M Age = 39) were recruited from social/sexual networking sites targeting MSM in 2010-2011. Participants reported multiple dimensions of sexual experience (pleasure, affection, and love) occurring at their last male-partnered sexual event, partner relationship, and sociodemographic characteristics. Across relationship categories, a sizeable percentage of Black MSM reported pleasure (72-87  % orgasmed, 57-82 % experienced high subjective pleasure) and affection (70-91 % kissed, 47-90 % cuddled). Love was primarily reported for events involving main partners (felt love for partner: 96 %; felt loved by partner: 97 %; verbalized love to partner: 89 %). Latent class analysis with MSM of all races, adjusting for partner relationship and sociodemographic characteristics, revealed three distinct profiles of sexual experience: affection and love (Class 1); affection in the absence of love (Class 2); and neither affection nor love (Class 3). Pleasure was probable across profiles. Some racial differences in profile probability were present, but no overall pattern emerged. Contrary to Black male stereotypes, Black MSM commonly reported pleasure, affection, and love at their last male-partnered sexual event and did not show a meaningful pattern of difference from other-race MSM in their likelihood of experiencing all three.

High prevalence of multiple syndemic conditions associated with sexual risk behavior and HIV infection among a large sample of Spanish- and Portuguese-speaking men who have sex with men in Latin America.

The HIV epidemic in Latin America is highly concentrated in men who have sex with men (MSM). In the United States, multiple co-occurring psychosocial conditions have been shown to act as intertwined epidemics to potentiate HIV transmission among MSM. To date, no study has examined the role of syndemics and condomless sex among MSM in Latin America. In 2012, an online survey was conducted among members of the largest social/sexual networking website for MSM in Latin America. Participants were asked about demographics, sexual behaviors, HIV/STI diagnoses, and psychosocial well-being, including depression, suicidal ideation, hazardous alcohol use, hard drug use during sex, history of childhood/adolescent sexual abuse, intimate partner violence, and sexual compulsivity. Multivariable logistic generalized estimation equations were used to assess the relationship of syndemic factors and (1) engagement in higher risk condomless anal sex and (2) self-report of prior HIV diagnosis. Among 24,274 survey respondents, 74.6 % of the sample had at least one syndemic factor. In an additive model, syndemics were associated with increased odds of higher risk condomless anal sex, ranging from adjusted odds ratio of 1.31 (95 % CI 1.20, 1.43) for one syndemic factor to 4.06 (95 % CI 3.25, 5.09) for 6/7 syndemic factors. Similarly, syndemics were associated with increased odds of HIV infection (p < .0001). This study provides initial evidence that intertwined syndemics increase HIV risk behavior and HIV infection among MSM in Latin America. In the Latin American context, comprehensive HIV prevention interventions for MSM should be developed and tested that simultaneously address co-occurring psychosocial conditions and HIV risk.

Epidemiology of sexual health in the virtual environment: a multinational online survey of Spanish- and Portuguese-speaking men who use an internet sexual networking site.

There is limited data on the sexual health of users of sexual networking websites for men who have sex with men (MSM) in Latin America. Members of a MSM-targeted social/sexual networking website in Latin America, Spain, and Portugal participated in an online sexual health survey. Among 36,063 respondents, nearly 90 % reported having anal or vaginal intercourse in the past 3 months. Among sexually active men, 53.2 % used condoms inconsistently. In the past year, 54 % of respondents reported undergoing sexually transmitted infections (STI) testing and 67 % reported testing yearly or more often for HIV. Self-reported HIV prevalence was 9.1 %. Differences were seen by geographic region. Unprotected intercourse with partners of different or unknown HIV status was associated with recent STI diagnosis (OR = 1.83, t = 13.15, d.f. = 21, p < .001) and HIV diagnosis (OR = 2.20, t = 14.00, d.f. = 21, p < .001). Online surveys are a promising tool for HIV/STI surveillance and prevention internationally to reach an important subset of MSM.

What's love got to do with it? Examinations of emotional perceptions and sexual behaviors among gay and bisexual men in the United States.

Men who have sex with men (MSM) continue to be disproportionately impacted by STIs and HIV. In addition to traditional risk factors, increasing attention has been given to the potential role of affective components of a sexual encounter, including mood state. To date, no study has described sexual behaviors engaged in by those who report being in love (or not) during a given sexual event. Internet-based survey data were collected from 24,787 gay and bisexual men who were members of online websites facilitating social or sexual interactions with other men. Measures included sociodemographics, recent sexual behavior history, sexual event characteristics, and perceptions of "love" with men's most recent male sexual partner. Participants' mean age was 39.2 years; ethnicities included white (84.6 %), Latino (6.4 %), and African American (3.6 %). Nearly all men (91 %) were matched by presence (I love him/he loves me), absence (I don't love him/he doesn't love me), or uncertainty (I don't know if I do/I don't know if he does) of love with their most recent sexual partner. Men who reported love for their partner and believed their partner loved them were significantly more likely to have engaged in behaviors such as cuddling and kissing on the mouth. Differences were also seen in regard to love and men's reports of anal intercourse and oral sex. Findings highlight differences in sexual behaviors based on perceptions of love and suggest the need to further explore how these differences influence sexual health.

Using a two-step method to measure transgender identity in Latin America/the Caribbean, Portugal, and Spain.

Few comparative data are available internationally to examine health differences by transgender identity. A barrier to monitoring the health and well-being of transgender people is the lack of inclusion of measures to assess natal sex/gender identity status in surveys. Data were from a cross-sectional anonymous online survey of members (n > 36,000) of a sexual networking website targeting men who have sex with men in Spanish- and Portuguese-speaking countries/territories in Latin America/the Caribbean, Portugal, and Spain. Natal sex/gender identity status was assessed using a two-step method (Step 1: assigned birth sex, Step 2: current gender identity). Male-to-female (MTF) and female-to-male (FTM) participants were compared to non-transgender males in age-adjusted regression models on socioeconomic status (SES) (education, income, sex work), masculine gender conformity, psychological health and well-being (lifetime suicidality, past-week depressive distress, positive self-worth, general self-rated health, gender related stressors), and sexual health (HIV-infection, past-year STIs, past-3 month unprotected anal or vaginal sex). The two-step method identified 190 transgender participants (0.54%; 158 MTF, 32 FTM). Of the 12 health-related variables, six showed significant differences between the three groups: SES, masculine gender conformity, lifetime suicidality, depressive distress, positive self-worth, and past-year genital herpes. A two-step approach is recommended for health surveillance efforts to assess natal sex/gender identity status. Cognitive testing to formally validate assigned birth sex and current gender identity survey items in Spanish and Portuguese is encouraged.

Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines.

PALB2/FANCN is a BRCA1- and BRCA2-interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient-derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q-FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST-1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild-type FCLs generated from first-degree relatives (P =1.04E-10 and P =9.68E-15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild-type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2-related cancers.