riation. Conclusions and relevance Compared with QHPs in the Northeast, QHPs in the South were almost 16 times as likely to require prior authorization for PrEP, and the reasons for these disparities are unknown. The prior authorization requirement is a possible barrier to PrEP access in the South, which is the region of the United States with the most annual new HIV diagnoses. There is limited regulation of QHPs’ prior authorization requirements. Federal- or state-level health policy laws may be necessary to remove this system-level barrier to ending the HIV epidemic in the United States.Importance The association of mental disorders with premature mortality published in the Global Burden of Disease (GBD) studies has been underestimated because these analyses have recommended using only a small number of mental disorders as causes of death to estimate years of life lost (YLL). Alternative methods have been introduced, such as estimating life-years lost (LYL), to compare individuals with mental disorders with the general population. Objectives To generate register-based YLL and LYL estimates and to use these measurement methods to assess the association of specific mental disorders with premature mortality. Design, setting, and participants This population-based cohort study included all persons with and without mental disorders aged 0 to 94 years who were living in Denmark between January 1, 2000, and December 31, 2015. Data were analyzed from January to December 2019. Main outcomes and measures Danish health registers were used to identify mental disorder diagnoses, dates of death, and causevel YLLs and LYLs, and both measurement methods are informative for health care planning. Compared with YLL, the novel LYL measurement approach may more precisely capture the association of mental disorders with premature mortality and facilitates the exploration of comorbidity and specific causes of death in individuals with mental disorders.Importance An increasing proportion of US smokers smoke at low intensity and not every day. Some nondaily smokers have always had this pattern, whereas others previously smoked daily. The effect of reducing the level of smoking from daily to nondaily smoking and the dose response at low smoking levels are poorly understood. Objective To evaluate risk of all-cause and cause-specific mortality among nondaily and daily cigarette smokers, by cigarettes per month, years after reducing from daily to nondaily smoking, and years since quitting. Design, setting, and participants A prospective cohort study using harmonized data from multiple cycles of the Tobacco Use Supplements to the Current Population Survey (TUS-CPS), linked to the National Death Index, were analyzed during the period from 2018 to 2020. Adults completed the 1992-1993, 1995-1996, 1998-1999, 2000, 2001-2002, 2003, 2006-2007, or 2010-2011 TUS-CPS. Cigarette smokers were classified as daily or nondaily users; current nondaily smokers were further categore years of nondaily smoking as lifelong nondaily smokers (HR vs never smokers, 1.73; 95% CI, 1.56-1.92). Yet, their risks were higher than former smokers who quit 10 or more years before (HR vs never smokers, 1.18; 95% CI, 1.15-1.22). Conclusions and relevance Although reducing smoking from daily to nondaily was associated with decreased mortality risk, cessation was associated with far greater benefit. Lifelong nondaily smokers have higher mortality risks than never smokers, even among those smoking 6 to 10 cigarettes per month. Thus, all smokers should quit, regardless of how infrequently they smoke.Importance There is a lack of studies exploring the performance of a deep learning survival neural network in non-small cell lung cancer (NSCLC). Objectives To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network. Design, setting, and participants In this population-based cohort study, a deep learning-based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59; P less then .001), which was verified by propensity score-matched groups. selleckchem The deep learning survival neural network model visualization was realized by a user-friendly graphic interface. Conclusions and relevance The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer-specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.Pharmacological inhibitors of Bruton tyrosine kinase (BTK) have revolutionized treatment of B-lymphocyte malignancies and show great promise for dampening autoimmunity. The predominant BTK inhibitors tether irreversibly by covalently binding to cysteine 481 in the BTK catalytic domain. Substitution of cysteine 481 for serine (C481S) is the most common mechanism for acquired drug resistance. We generated a novel C481S knock-in mouse model and, using a battery of tests, no overt B-lymphocyte phenotype was found. B lymphocytes from C481S animals were resistant to irreversible, but sensitive to reversible, BTK inhibitors. In contrast, irreversible inhibitors equally impaired T-lymphocyte activation in mice, mimicking the effect of treatment in patients. This demonstrates that T-lymphocyte blockage is independent of BTK. We suggest that the C481S knock-in mouse can serve as a useful tool for the study of BTK-independent effects of irreversible inhibitors, allowing for the identification of novel therapeutic targets and pinpointing potential side effects.