The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Mental health and associated sexual health behaviours in a sample of young people attending a music festival in Melbourne, Victoria

Poor mental health has previously been associated with risky sexual health behaviours among young people internationally and in clinical samples, but little is known about this relationship in non-clinical settings. We conducted a cross-sectional survey with a convenience sample of 1345 Australians aged 15–29. Multivariable logistic regression was used to identify sexual health behaviours independently associated with recent poor mental health including contraception use, STI testing, sexting and age at first sexual intercourse. Recent poor mental health was reported by 29.7 % of participants and independently associated with female gender (OR 1.8; 95 % CI 1.4–2.4), not identifying as heterosexual (OR 3.0; 95 % CI 2.1–4.4) and young age at first sexual intercourse among female participants (OR 1.4; 95 % CI 1.0–2.0). Results suggest mental health is largely driven by variables other than sexual health behaviours, although youth mental health services should consider inclusion of sexual health promotion within the scope of their services

Young Australians' use of pornography and associations with sexual risk behaviours

Abstract Objectives: Amid public health concern that rising pornography use may have a negative impact on young people's health and wellbeing, we report prevalence of pornography viewing and explore factors associated with viewing frequency and age at first viewing. Methods: Cross‐sectional online survey in a convenience sample of Victorians aged 15 to 29 years recruited via social media. Results: Ever viewing pornography was reported by 815 of 941 (87%) participants. The median age at first pornography viewing was 13 years for men and 16 years for women. More frequent pornography viewing was associated with male gender, younger age, higher education, non‐heterosexual identity, ever having anal intercourse and recent mental health problems. Younger age at first pornography viewing was associated with male gender, younger current age, higher education, non‐heterosexual identity, younger age at first sexual contact and recent mental health problems. Conclusions: Pornography use is common and associated with some health and behavioural outcomes. Longitudinal research is needed to determine the causal impact of pornography on these factors. Implications for public health: Viewing pornography is common and frequent among young people from a young age and this needs to be considered in sexuality education

I am yet to encounter any survey that actually reflects my life:A qualitative study of inclusivity in sexual health research

Abstract Background Heteronormativity describes a set of norms and assumptions pertaining to heterosexual identities and binary gender. In 2015, we conducted our annual Sex, Drugs and Rock’n’Roll study, an online health survey of over 1000 Victorians aged 15–29 years. Feedback from participants suggested that our survey contained heteronormative language. In response to this, we aimed to make inclusive changes to our survey via consultation with young gender and sexually diverse (GSD) people. Methods We conducted two semi-structured focus groups in Melbourne with a total of 16 participants (age range: 21–28 years). Participants were mostly cisgender women, and there were two transgender participants and one non-binary participant. Participants also had a range of sexual identities including lesbian, queer, bisexual, pansexual, and asexual. Focus group discussions were transcribed verbatim and analysed thematically. Results Most participants indicated heteronormativity affects their lives in multiple ways, noting its impacts on access to sexual healthcare, invalidating sexual experiences and miscommunication in forms and surveys. Overall, participants emphasised the need for sexual health research to avoid assumptions about behaviour, to be clear and eliminate question ambiguity and avoiding treating gender as binary. Participants also discussed how the Sex, Drugs and Rock’n’Roll survey could address a range of sexual behaviours and experiences, rather than focusing on penetrative sex, which many participants found invalidating. Conclusions Our findings have important implications for future health surveys aimed at general populations. We present recommendations that encourage research to be more inclusive to ensure data collection from GSD participants is respectful and rigorous

Polygenic risk scores for autoimmune related diseases are significantly different in cancer exceptional responders

Abstract A small number of cancer patients respond exceptionally well to therapies and survive significantly longer than patients with similar diagnoses. Profiling the germline genetic backgrounds of exceptional responder (ER) patients, with extreme survival times, can yield insights into the germline polymorphisms that influence response to therapy. As ERs showed a high incidence in autoimmune diseases, we hypothesized the differences in autoimmune disease risk could reflect the immune background of ERs and contribute to better cancer treatment responses. We analyzed the germline variants of 51 ERs using polygenic risk score (PRS) analysis. Compared to typical cancer patients, the ERs had significantly elevated PRSs for several autoimmune-related diseases: type 1 diabetes, hypothyroidism, and psoriasis. This indicates that an increased genetic predisposition towards these autoimmune diseases is more prevalent among the ERs. In contrast, ERs had significantly lower PRSs for developing inflammatory bowel disease. The left-skew of type 1 diabetes score was significant for exceptional responders. Variants on genes involved in the T1D PRS model associated with cancer drug response are more likely to co-occur with other variants among ERs. In conclusion, ERs exhibited different risks for autoimmune diseases compared to typical cancer patients, which suggests that changes in a patient’s immune set point or immune surveillance specificity could be a potential mechanistic link to their exceptional response. These findings expand upon previous research on immune checkpoint inhibitor-treated patients to include those who received chemotherapy or radiotherapy