An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Identity Development Among Racially Diverse Transgender and Similarly Gender Nonconforming LGB Youth

Several distinct yet overlapping literatures have contributed to understanding the trajectories of gender nonconforming children. However, these often fail to adequately distinguish the experiences of those who share similar experiences of childhood gender nonconformity, but come to self-identify in various ways. To address this gap, transgender identifying youth were matched with non-transgender identifying youth of similar levels of childhood gender nonconformity (N=20, ages 19 to 23, 75% racial/ethnic minority), and developmental semi-structured interviews were conducted. Qualitative data analysis was guided by an ecological framework, which identified the characteristics of the youth’s self-understandings (identity, physical self, self presentation, interests/activities, attractions/behavior) and the settings (e.g., school, family, community centers, media) that they interactively negotiated throughout development. Focus on the self codes revealed multiple related, distinct, and interactive dimensions of gender and sexuality, which also changed over time. These dimensions will be discussed, along with the similarities and differences found across birth sex (male, female) and current gender identity (transgender, primarily non-transgender). Overall, results highlight the complexity and diversity of experience within the transgender umbrella. They also reinforce the importance of youth’s exposure to a range of ways of making meaning of one’s gender and sexual orientation related experiences, and support a move away from disorder based models of gender variance to those that focus on the supportiveness of the context

Coping With LGBT and racial-ethnic-related stressors: A mixed-methods study of LGBT youth of color

This study examines how racial-ethnic minority lesbian, gay, bisexual, and transgender (LGBT) youth cope with both racial-ethnic and LGBT-related stress. Within a sample of 213 LGBT youth of color, the present study presents (1) quantitative and qualitative results from an approach and avoidance-based measure of parental racial coping socialization across six conversation domains, and (2) qualitative responses regarding LGBT stressors and associated coping strategies. The emphasis on approach versus avoidance varied across the racial-ethnic conversation domains. However, both racial-ethnic- and LGBT-related coping strategies emphasized a combination of cognitive and behavioral strategies. Similarities and differences also existed in the types of stressors encountered across racial-ethnic and LGBT statuses. We discuss the potential for coping skill transfer across these minority statuses

Setting a research agenda in trans health: An expert assessment of priorities and issues by trans and nonbinary researchers

Background: This article is by a group of trans and nonbinary researchers and experts in the field of trans health who have conducted an analysis of trans health research needs. Aims: To highlight topics that need further research and to outline key considerations for those conducting research in our field. Methods: The first author conducted semi-structured interviews with all co-authors, and these were used to create a first draft of this manuscript. This draft was circulated to all authors, with edits made until consensus was reached among the authors. Results: More comprehensive long-term research that centers trans people’s experiences is needed on the risks and benefits of gender affirming hormones and surgeries. The trans health research field also needs to have a broader focus beyond medical transition or gender affirmation, including general health and routine healthcare; trans people’s lives without, before, and after medical gender affirmation; and sexuality, fertility, and reproductive healthcare needs. More research is also needed on social determinants of health, including ways to make healthcare settings and other environments safer and more supportive; social and legal gender recognition; the needs of trans people who are most marginalized; and the ways in which healing happens within trans communities. The second part of this article highlights key considerations for researchers, the foremost being acknowledging trans community expertise and centering trans community members’ input into research design and interpretation of findings, in advisory and/or researcher roles. Ethical considerations include maximizing benefits and minimizing harms (beneficence) and transparency and accountability to trans communities. Finally, we note the importance of conferences, grant funding, working with students, and multidisciplinary teams. Discussion: This article outlines topics and issues needing further consideration to make the field of trans health research more responsive to the needs of trans people. This work is limited by our authorship group being mostly White, all being Anglophone, and residing in the Global North