Characteristics Associated With Mental Health Treatment Prior to Suicide Among Youth in the United States.

OBJECTIVE: To examine individual and contextual characteristics associated with receipt of mental health treatment prior to youth suicide. METHOD: Data from the US National Violent Death Reporting System, Area Health Resource File, and Social Vulnerability Index were used to examine characteristics associated with receipt of mental health treatment within 2 months before death among youth suicide decedents aged 5 to 17 years from 2013 to 2020 (N = 6,229). The association between individual (demographic, precipitating circumstances, and clinical characteristics) and contextual-level variables (county health resources, Social Vulnerability Index) and mental health service use was modeled using logistic regression. RESULTS: Mental health treatment was received by 31.6% of youth suicide decedents (n = 1,967) in the 2 months before suicide. Male individuals and youth from all racial and ethnic minority groups were less likely to receive mental health treatment in the 2 months prior to suicide, as were youth residing in non-metropolitan counties and living in counties characterized by high compared to low levels of social vulnerability. A history of family problems, a recent crisis, criminal/legal problems, and suicidal thoughts and attempts were associated with increased odds of receiving mental health services. CONCLUSION: Youth suicide decedents who were male, members of a racial or ethnic minority group, and residing in counties that are non-metropolitan and/or socially disadvantaged were less likely to have received mental health services in the months prior to death. Suicide prevention efforts that focus on improving access to care are essential for these vulnerable populations at risk for suicide.

Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy.

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies are particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment of tumors affects CAR-T cells, limiting the treatment's effectiveness and safety. Therefore, enhancing CAR-T cell infiltration capacity and resolving the immunosuppressive responses within the tumor microenvironment could boost the anti-tumor effect. Specific strategies include structurally altering CAR-T cells combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring the tumor microenvironment and the status of CAR-T cells is beneficial in further investigating the viability of such strategies and advancing CAR-T cell therapy.

Computationally efficient, exact, covariate-adjusted genetic principal component analysis by leveraging individual marker summary statistics from large biobanks.

The popularization of biobanks provides an unprecedented amount of genetic and phenotypic information that can be used to research the relationship between genetics and human health. Despite the opportunities these datasets provide, they also pose many problems associated with computational time and costs, data size and transfer, and privacy and security. The publishing of summary statistics from these biobanks, and the use of them in a variety of downstream statistical analyses, alleviates many of these logistical problems. However, major questions remain about how to use summary statistics in all but the simplest downstream applications. Here, we present a novel approach to utilize basic summary statistics (estimates from single marker regressions on single phenotypes) to evaluate more complex phenotypes using multivariate methods. In particular, we present a covariate-adjusted method for conducting principal component analysis (PCA) utilizing only biobank summary statistics. We validate exact formulas for this method, as well as provide a framework of estimation when specific summary statistics are not available, through simulation. We apply our method to a real data set of fatty acid and genomic data.

Searching for synergistic calcium antagonists and novel therapeutic regimens for coronary heart disease therapy from a Traditional Chinese Medicine, Suxiao Jiuxin Pill.

Coronary heart disease is a vital cause of morbidity and mortality worldwide, and calcium channel blockers (CCBs) are important drugs that can be used to treat cardiovascular diseases. Suxiao Jiuxin Pill (SX), a traditional Chinese medicine, is widely used as an emergency drug for coronary heart disease therapy. However, understanding its potential mechanism in intracellular calcium concentration ([Ca2+]i) modulation remains a challenge. To identify the active pharmacological ingredients (APIs) and reveal a novel combination therapy for ameliorating cardiovascular diseases, the ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) combined with a dual-luciferase reporter [Ca2+]i assay system was applied. Ligustrazine, ferulic acid, senkyunolide I, senkyunolide A and ligustilide were identified as potential calcium antagonists in SX, and the combination of ligustrazine and senkyunolide A showed synergetic calcium antagonistic activity. Additionally, the synergetic mechanism was further investigated by live-imaging analysis with the Ca2+ indicator fluo-4/AM by monitoring fluorescence changes. Our results indicated that ligustrazine can block voltage-operated Ca2+ channels (VDCCs) effectively and senkyunolide A can exert an inhibition effect mostly on ryanodine receptors (RYRs) and partly on VDCCs. Finally, an arterial ring assay showed that the combination of ligustrazine and senkyunolide A exerted a better vasodilatation function than using any components alone. In this study, we first revealed that a pair of natural APIs in combination acting on VDCCs and RYRs was more effective on vasodilatation by regulating [Ca2+]i.