A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination.

Quantitative metrics for vaccine-induced T-cell responses are an important need for developing correlates of protection and their use in vaccine-based medical management and population health. Molecular TCR analysis is an appealing strategy but currently requires a targeted methodology involving complex integration of ex vivo data (antigen-specific functional T-cell cytokine responses and TCR molecular responses) that uncover only public antigen-specific metrics. Here, we describe an untargeted private TCR method that measures breadth and depth metrics of the T-cell response to vaccine challenge using a simple pre- and post-vaccine subject sampling, TCR immunoseq analysis, and a bioinformatic approach using self-organizing maps and GLIPH2. Among 515 subjects undergoing SARS-CoV-2 mRNA vaccination, we found that breadth and depth metrics were moderately correlated between the targeted public TCR response and untargeted private TCR response methods. The untargeted private TCR method was sufficiently sensitive to distinguish subgroups of potential clinical significance also observed using public TCR methods (the reduced T-cell vaccine response with age and the paradoxically elevated T-cell vaccine response of patients on anti-TNF immunotherapy). These observations suggest the promise of this untargeted private TCR method to produce T-cell vaccine-response metrics in an antigen-agnostic and individual-autonomous context.

Management of suicide and self-harm risk by the National Mental Health Helpline in the State of Qatar.

BACKGROUND: Suicide is a serious public health problem. AIMS: To investigate the sociodemographic and clinical features of callers (patients) classed by the Qatar National Mental Health Helpline (NMHH) as moderate to high priority based on the risk of self-harm or suicide during the COVID-19 pandemic. METHOD: The study design was a retrospective chart review of patients who contacted the helpline in the first 12 months, starting 1 April 2020. Data of those classed as moderate to high priority based on risk to self were collected using a specifically designed form. Absolute and relative frequencies for each of the studied categorical variables were determined. RESULTS: Four hundred and ninety-eight patients were included. More than half were female. The mean age was 32 years (range 8-85 years). Two-thirds of patients were from Arab countries and more than half of all patients had contacted mental health services for the first time. The most common symptoms elicited included suicidal thoughts, depressed mood and disturbed sleep. The most common psychiatric disorders were depression and generalised anxiety disorder. Most patients were seen within 4 h and received psychiatric interventions. Virtually all patients received non-pharmacological interventions; only 38.5% received pharmacological interventions. The majority had follow-up appointments arranged with mental health services. CONCLUSIONS: People from the Indian subcontinent and males proportionally approached services less, which may reflect stigma. The NMHH improved access to care for patients considered at risk to self and prevented hospital admissions. The NMHH offers a valuable additional choice to patients and assists in prevention and management of suicidal behaviour and other mental health difficulties.

Dietary Patterns and Their Association With Symptoms Activity in Inflammatory Bowel Diseases.

BACKGROUND: Existing studies on diet and inflammatory bowel disease (IBD) have largely focused on evaluating the effects of single nutrients or whole predesigned diets but not on evaluating the effects of diverse dietary patterns. This study applied unsupervised methods to identify dietary patterns of individuals with IBD and evaluated their association with symptoms activity. METHODS: This retrospective study of adults with IBD collected current clinical data and typical diet recalled from the time when in clinical remission. Discrete dietary structures were defined by k-means clustering. Multivariable logistic regression evaluated the relationship between diet clusters and the presence of active symptoms, while adjusting for age, sex, disease duration, disease behavior, and medication use. RESULTS: Of 691 participants, 36% had Crohn's disease (CD) and 64% had ulcerative colitis (UC) or IBD-unclassified. Five major dietary clusters were identified: 2 resembled a Western diet (WD) (WD1, WD2), 1 resembled a balanced diet, and 2 resembled a plant-based diet (PB) (PB1, PB2). Compared with WD1, PB2 was associated with lower odds of active symptoms for CD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.83) and UC (OR, 0.31; 95% CI, 0.15-0.62). PB1 was associated with lower odds of active symptoms for participants with UC (OR, 0.45; 95% CI, 0.23-0.90) but not for participants with CD (OR, 0.95; 95% CI, 0.36-2.51). CONCLUSIONS: Diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with CD.

The study used machine learning methods to provide minimally biased classifications of dietary patterns among individuals with inflammatory bowel diseases, followed by an evaluation of the association between the different diet clusters and symptoms activity.