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We reported computed tomographic (CT) imaging findings of 3 patients with coronavirus disease 2019 (COVID-19) pneumonia with initially negative results before CT examination and finally confirmed positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reversetranscription polymerase chain reaction assay.

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BackgroundLimited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Relevant data about mortality of XDR-TB patients in literature are limited and likely underestimate the real situation in China, since the majority of patients with XDR-TB are lost to follow-up after discharge from TB hospitals. In this study, we sought to investigate the mortality and associated risk factors of Human Immunodeficiency Virus (HIV)-negative patients with XDR-TB in China.MethodsAll patients who were diagnosed with XDR-TB for the first time in four TB care centers across China between March 2013 and February 2015 were consecutively enrolled. Active tracking through contacting patients or family members by phone or home visit was conducted to obtain patients’ survival information by February 2017. Multivariable Cox regression models were used to evaluate factors associated with mortality.ResultsAmong 67 patients enrolled, the mean age was 48.7 (Standard Deviation [SD] = 16.7) years, and 51 (76%) were men. Fourteen patients (21%) were treatment naïve at diagnosis indicating primary transmission. 58 (86.8%) patients remained positive for sputum smear or culture when discharged. During a median follow-up period of 32 months, 20 deaths occurred, with an overall mortality of 128 per 1000 person-years. Among patients who were dead, the median survival was 5.4 months (interquartile range [IQR]: 2.2–17.8). Seventeen (85%) of them died at home, among whom the median interval from discharge to death was 8.4 months (IQR: 2.0–18.2). In Cox proportional hazards regression models, body mass index (BMI) < 18.5 kg/m2 (adjusted hazard ratio [aHR] = 4.5, 95% confidence interval [CI]: 1.3–15.7), smoking (aHR = 4.7, 95%CI:1.7–13.2), or a clinically significant comorbidity including heart, lung, liver, or renal disorders or auto-immune diseases (aHR = 3.5, 95%CI: 1.3–9.4), were factors independently associated with increased mortality.ConclusionOur study suggested an alarming situation of XDR-TB patients in China with a sizable proportion of newly transmitted cases, a high mortality rate, and a long period in community. This observation calls for urgent actions to improve XDR-TB case management in China, including providing regimens with high chances of cure and palliative care, and enhanced infection control measures.

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ObjectiveTo investigate the picture between vitamin D levels and clinical outcomes of SARS-CoV-2 Omicron subvariant BA.2 in children.MethodsA retrospective, longitudinal cohort study was performed. All included hospitalized cases were divided into the sufficient (sVD) and insufficient vitamin D (iVD) groups according to whether their serum 25-hydroxyvitamin D [25(OH)D] concentration was ≥30 ng/mL. Dynamic changes in clinical parameters were observed for seven time periods within 28 days after admission.ResultsSerum 25(OH)D concentrations were significantly negatively correlated with age in the included cases (r = −0.6; P &lt; 0.001). Compared with the iVD group (n = 80), the sVD group (n = 36) had higher interleukin-6 (18.4 vs. 12.9; P = 0.003) within the first day; higher procalcitonin within the first (0.15 vs. 0.1; P = 0.03), 2–3 (0.14 vs. 0.07; P = 0.03), 4–5 (0.21 vs. 0.07; P = 0.02) days; more lymphocytes within the first (1.6 vs. 1.2; P = 0.02), 2–3 (3.7 vs. 2; P = 0.001), 4–5 (3.9 vs. 2.1; P = 0.01) and 6–7 (4.9 vs. 2.7; P = 0.02) days; notably, higher cycle threshold for N gene (30.6 vs 19.8; P = 0.03) or ORF1ab gene (31.4 vs 20.1; P = 0.03) within 2 to 3 days. Pneumonia lesions were found in eleven and six cases in the iVD and sVD groups, respectively, without significant difference on computed tomography at admission. Six out of eleven and five out of six had a repeat computed tomography after 1–2 weeks. Lesion improvement was more significant in the sVD group (P = 0.04).ConclusionsChildren with vitamin D insufficiency might have poorer clinical outcomes in Omicron subvariant BA.2 infection, especially in older pediatric patients. Further studies are needed to assess effectiveness of supplements in reducing the same.

The inhibition of glutaminase 1 (GLS1) represents a potential treatment of malignant tumors. Structural analysis led to the design of a novel series of macrocyclic GLS1 allosteric inhibitors. Through extensive structure–activity relationship studies, a promising candidate molecule 13b (LL202) was identified with robust GLS1 inhibitory activity (IC50 = 6 nM) and high GLS1 binding affinity (SPR, K d = 24 nM; ITC, K d = 37 nM). The X-ray crystal structure of the 13b–GLS1 complex was resolved, revealing a unique binding mode and providing a novel structural scaffold for GLS1 allosteric inhibitors. Importantly, 13b clearly adjusted the cellular metabolites and induced an increase in the ROS level by blocking glutamine metabolism. Furthermore, 13b exhibited a similar in vivo antitumor activity as CB839. This study adds to the growing body of evidence that macrocyclization provides an alternative and complementary approach for the design of small-molecule inhibitors, with the potential to improve the binding affinity to the targets.