Background Males experience increased severity of illness and mortality from SARS-CoV-2 compared to females but the mechanisms of male susceptibility are unclear. Methods We performed a retrospective cohort analysis of SARS-CoV-2 testing and admission data at 5 hospitals in the Maryland/Washington DC area. Using age-stratified logistic regression models we quantified the impact of male sex on the risk of the composite outcome of severe disease or death (WHO score 5-8), and tested the impact of demographics, comorbidities, health behaviors, and laboratory inflammatory markers on the sex effect. Results Among 213,175 SARS-CoV-2 tests, despite similar positivity rates, males in age strata between 18 and 74 years were more frequently hospitalized. For the 2,626 hospitalized individuals, clinical inflammatory markers (IL-6, CRP, ferritin, absolute lymphocyte count and neutrophil:lymphocyte ratio) were more favorable for females than males (p< 0.001). Among 18-49 year-olds, male sex carried a higher risk of severe outcomes; both early (odds ratio (OR) 3.01, 95%CI 1.75,5.18) and at peak illness during hospitalization (OR 2.58, 95%CI 1.78,3.74). Despite multiple differences in demographics, presentation features, comorbidities and health behaviors, these variables did not change the association of male sex with severe disease. Only clinical inflammatory marker values modified the sex effect, reducing the OR for severe outcomes in males ages 18-49 years to 1.81 (95%CI 1.00,3.26) early and 1.39 (95%CI 0.93,2.08) at peak illness. Conclusions Higher inflammatory laboratory test values were associated with increased risk of severe COVID-19 for males. A sex-specific inflammatory response to SARS-CoV-2 infection may underlie the sex differences in outcomes.

Surgery cancellations waste scarce operative resources and hinder patients’ access to operative services. In this study, the Wilcoxon and chi-square tests were used for predictor selection, and three machine learning models – random forest, support vector machine, and XGBoost – were used for the identification of surgeries with high risks of cancellation. The optimal performances of the identification models were as follows: sensitivity − 0.615; specificity − 0.957; positive predictive value − 0.454; negative predictive value − 0.904; accuracy − 0.647; and area under the receiver operating characteristic curve − 0.682. Of the three models, the random forest model achieved the best performance. Thus, the effective identification of surgeries with high risks of cancellation is feasible with stable performance. Models and sampling methods significantly affect the performance of identification. This study is a new application of machine learning for the identification of surgeries with high risks of cancellation and facilitation of surgery resource management.

Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called “97Q” and “myogenic” SBMA models. The 97Q model globally overexpresses a full length human AR with 97 glutamine repeats whereas the myogenic model of SBMA overexpresses a wild-type rat androgen receptor (AR) only in skeletal muscle fibers. Using quantitative PCR, we find that muscle BDNF mRNA declines in an androgen-dependent manner in both models, paralleling changes in motor function, with robust deficits (6-8 fold) in both fast and slow twitch muscle of impaired Tg males. Castration rescues or reverses disease-related deficits in muscle BDNF mRNA in both models, paralleling its effect on motor function. Moreover, when disease is acutely induced in Tg females, both motor function and muscle BDNF mRNA expression plummet, with the deficit in muscle BDNF emerging before overt motor dysfunction. That androgen-dependent motor dysfunction is tightly associated with a robust and early down-regulation of muscle BDNF mRNA suggests that BDNF delivered to muscle may have therapeutic value for SBMA.

Medicine-food homology is a long-standing concept in traditional Chinese medicine. YiNianKangBao (YNKB) tea is a medicine-food formulation based on Sichuan dark tea (Ya’an Tibetan tea), which is traditionally used for its lipid-lowering properties. In this study, we evaluated the effects of YNKB on dyslipidemia and investigated the mechanism underlying its correlation with gut microbiota and serum metabolite regulation. Wild-type mice were fed a normal diet as a control. Male ApoE-/- mice were randomly divided into three high-fat diet (HFD) groups, a model group, and two treated groups (100, 400 mg/kg/d for low, high-dose), and fed by gavage for 12 weeks. Serum lipid levels, composition of gut microbiota, and serum metabolites were then analyzed before treatment with YNKB. We extracted the ingredients of YNKB in boiled water for one hour. YNKB supplementation at a high dose of 400 mg/kg/day reduced bodyweight gains (relative epididymal fat pad and liver weight), and markedly attenuated serum lipid profiles and atherosclerosis index, with no significant differences present between the low-dose treatment and HFD groups. Gut microbiota and serum metabolic analysis indicated that significant differences were observed between normal, HFD, and YNKB treatment groups. These differences in gut microbiota exhibited strong correlations with dyslipidemia-related indexes and serum metabolite levels. Oral administration of high-dose YNKB also showed significant lipid-lowering activity against hyperlipidemia in apoE-deficient mice, which might be associated with composition alterations of the gut microbiota and changes in serum metabolite abundances. These findings highlight that YNKB as a medicine-food formulation derived from Sichuan dark tea could prevent dyslipidemia and improve the understanding of its mechanisms and the pharmacological rationale for preventive use.