The Longitudinal Analysis of Convergent Antibody VDJ Regions in SARS-CoV-2 Positive Patients Using RNA-seq

The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has infected over 600 million individuals and caused over 6.5 million deaths. To understand the immune response individuals have from the SARS-CoV-2 infection, we studied the immunoglobulins against the viruss antigens. The diversified complementarity determining region 3 (CDR3) can be used to characterize an antibody. We downloaded four public RNA-seq data sets that were collected be-tween March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. In total, there were 269 SARS-CoV-2 positive patients and 26 negative patients who served as a control group. Samples were grouped based on their SARS-CoV-2 variant type and/or the time they were collected. Among 629,137 immunoglobulin V(D)J sequences identified by reconstructing the V(D)J sequences, we found 1011 common V(D)Js (same V gene, J gene and CDR3 sequences in each SARS-CoV-2 positive group) shared by more than one patient in each group and no common V(D)Js were from the negative control group. In our clustering analysis, we identified 129 convergent clusters from the SARS-CoV-2 positive groups. One of these convergent clusters matched the protein sequence of crystal 3D structures of the antibodies against SARS-CoV-2 in the Protein Data Bank (PDB). In our longitudinal analysis between the Alpha and Omicron variant, we found 2.7% of common CDR3s were shared although the longitudinal profiling of common V(D)Js was variant specific. Although diverse immunoglobulin profiles were observed, the convergence of common V(D)Js suggests that there exists antibodies with similar antigenic specificities across patients in different groups over various stages of the pandemic.

Evaluation of external contamination on the vial surfaces of some hazardous drugs that commonly used in Chinese hospitals and comparison between environmental contamination generated during robotic compounding by IV: Dispensing robot vs. manual compounding in biological safety cabinet.

OBJECTIVES: The aims of the study were to evaluate the external contamination of hazardous drug vials used in Chinese hospitals and to compare environmental contamination generated by a robotic intelligent dispensing system (WEINAS) and a manual compounding procedure using a biological safety cabinet (BSC). METHODS: Cyclophosphamide, fluorouracil, and gemcitabine were selected as the representative hazardous drugs to monitor surface contamination of vials. In the comparative analysis of environmental contamination from manual and robotic compounding, wipe samples were taken from infusion bags, gloves, and the different locations of the BSC and the WEINAS robotic system. In this study, high-performance liquid chromatography coupled with double mass spectrometer (HPLC-MS/MS) was employed for sample analysis. RESULTS: (1) External contamination was measured on vials of all three hazardous drugs. The contamination detected on fluorouracil vials was the highest with an average amount up to 904.33 ng/vial, followed by cyclophosphamide (43.51 ng/vial), and gemcitabine (unprotected vials of 5.92 ng/vial, protected vials of 0.66 ng/vial); (2) overall, the environmental contamination induced by WEINAS robotic compounding was significantly reduced compared to that by manual compounding inside the BSC. Particularly, compared with manual compounding, the surface contamination on the infusion bags during robotic compounding was nearly nine times lower for cyclophosphamide (10.62 ng/cm2 vs 90.43 ng/cm2), two times lower for fluorouracil (3.47 vs 7.52 ng/cm2), and more than 23 times lower for gemcitabine (2.61 ng/cm2 vs 62.28 ng/cm2). CONCLUSIONS: The external contamination occurred extensively on some hazardous drug vials that commonly used in Chinese hospitals. Comparison analysis for both compounding procedures revealed that robotic compounding can remarkably reduce environmental contamination.

Predictive value of MRI pelvic measurements for "difficult pelvis" during total mesorectal excision / 中华胃肠外科杂志

Objective: Total mesorectal resection (TME) is difficult to perform for rectal cancer patients with anatomical confines of the pelvis or thick mesorectal fat. This study aimed to evaluate the ability of pelvic dimensions to predict the difficulty of TME, and establish a nomogram for predicting its difficulty. Methods: The inclusion criteria for this retrospective study were as follows: (1) tumor within 15 cm of the anal verge; (2) rectal cancer confirmed by preoperative pathological examination; (3) adequate preoperative MRI data; (4) depth of tumor invasion T1-4a; and (5) grade of surgical difficulty available. Patients who had undergone non-TME surgery were excluded. A total of 88 patients with rectal cancer who underwent TME between March 2019 and November 2021 were eligible for this study. The system for scaling difficulty was as follows: Grade I, easy procedure, no difficulties; Grade II, difficult procedure, but no impact on specimen quality (complete TME); Grade III, difficult procedure, with a slight impact on specimen quality (near-complete TME); Grade IV: very difficult procedure, with remarkable impact on specimen quality (incomplete TME). We classified Grades I-II as no surgical difficulty and grades III-IV as surgical difficulty. Pelvic parameters included pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the difficulty of TME, and a nomogram predicting the difficulty of the procedure was established. Results: The study cohort comprised 88 patients, 30 (34.1%) of whom were classified as having undergone difficult procedures and 58 (65.9%) non-difficult procedures. The median age was 64 years (56-70), 51 patients were male and 64 received neoadjuvant therapy. The median pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance were 12.0 cm, 11.0 cm, 8.6 cm, 4.9 cm, 12.6 cm, 3.7 cm, 3.0 cm, 13.3 cm, 10.2 cm, and 12.2 cm, respectively. Multivariable analyses showed that preoperative chemoradiotherapy (OR=4.97,95% CI: 1.25-19.71, P=0.023), distance between the tumor and the anal verge (OR=1.31, 95% CI: 1.02-1.67, P=0.035) and pubic tubercle height (OR=3.36, 95% CI: 1.56-7.25, P=0.002) were associated with surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC = 0.795, 95%CI: 0.696-0.895). Conclusion: Our research demonstrated that our system for scaling surgical difficulty of TME is useful and practical. Preoperative chemoradiotherapy, distance between tumor and anal verge, and pubic tubercle height are risk factors for surgical difficulty. These data may aid surgeons in planning appropriate surgical procedures.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus vectored vaccines expressing spike (S) protein have advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Behavioural changes during the COVID-19 pandemic: Results of a nationwide survey in Singapore

INTRODUCTION@#As part of infection control measures for COVID-19, individuals have been encouraged to adopt both preventive (such as handwashing) and avoidant behavioural changes (e.g. avoiding crowds). In this study, we examined whether demographics predicted the likelihood that a person would adopt these behaviours in Singapore.@*METHODS@#A total of 1,145 participants responded to an online survey conducted between 7 March and 21 April 2020. We collected demographic information and asked participants to report which of 17 behaviour changes they had undertaken because of the COVID-19 outbreak. Regression analyses were performed to predict the number of behavioural changes (preventive, avoidant, and total) as a function of demographics. Finally, we sought to identify predictors of persons who declared that they had not undertaken any of these measures following the outbreak.@*RESULTS@#Most participants (97%) reported at least one behavioural change on account of the pandemic, with changes increasing with the number of local COVID-19 cases (@*CONCLUSION@#Our characterisation of behavioural changes provides a baseline for public health advisories. Moving forward, health authorities can focus their efforts on encouraging segments of the population who do not readily adopt infection control measures against COVID-19.

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic / 医学前沿

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Patient characteristics, clinical care, resource use, and outcomes associated with hospitalization for COVID-19 in the Toronto area

BackgroundPatient characteristics, clinical care, resource use, and outcomes associated with hospitalization for coronavirus disease (COVID-19) in Canada are not well described. MethodsWe described all adult discharges from inpatient medical services and medical-surgical intensive care units (ICU) between November 1, 2019 and June 30, 2020 at 7 hospitals in Toronto and Mississauga, Ontario. We compared patients hospitalized with COVID-19, influenza and all other conditions using multivariable regression models controlling for patient age, sex, comorbidity, and residence in long-term-care. ResultsThere were 43,462 discharges in the study period, including 1,027 (3.0%) with COVID-19 and 783 (2.3%) with influenza. Patients with COVID-19 had similar age to patients with influenza and other conditions (median age 65 years vs. 68 years and 68 years, respectively, SD<0.1). Patients with COVID-19 were more likely to be male (59.1%) and 11.7% were long-term care residents. Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared to influenza, patients with COVID-19 had significantly greater mortality (unadjusted 19.9% vs 6.1%, aRR: 3.47, 95%CI: 2.57, 4.67), ICU use (unadjusted 26.4% vs 18.0%, aRR 1.52, 95%CI: 1.27, 1.83) and hospital length-of-stay (unadjusted median 8.7 days vs 4.8 days, aRR: 1.40, 95%CI: 1.20, 1.64), and not significantly different 30-day readmission (unadjusted 8.6% vs 8.2%, aRR: 1.01, 95%CI: 0.72, 1.42). InterpretationAdults hospitalized with COVID-19 during the first wave of the pandemic used substantial hospital resources and suffered high mortality. COVID-19 was associated with significantly greater mortality, ICU use, and hospital length-of-stay than influenza.

Syndromic Surveillance for COVID-19 in Canada

BackgroundSyndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. MethodsData sources consisted of two distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. ResultsWe found that 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month over March-April 2020. Across the three surveys, SARS-CoV-2-testing was reported in 2-9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Metis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. InterpretationThe low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of current SARS-CoV-2 testing rates.

Study on relevant imaging factors for recurrence of cerebral ischemic stroke / 实用放射学杂志

Objective To analyze the imaging characteristics of patients with recurrence of acute cerebral ischemic stroke,select and predict relevant imaging factors,to guide clinical treatment and prevention.Methods Data of 30 patients with acute cerebral ischemic stroke (recurrent group)and 40 patients with primary cerebral ischemic stroke (non recurrent group)were collected.Imaging characteristics of first onset of recurrent group and non recurrent group were analyzed.Leukoaraiosis,a large area of infarction,cortical infarction,carotid artery plaque,arteriosclerosis,incomplete Willis ring,watershed infarction and other risk factors were screened,to determine the association between these risk factors and recurrent cerebral ischemic stroke.Results Recurrence of cerebral ischemic stroke was associated with leukoaraiosis,carotid artery plaque and incomplete Willis ring (P values were 0.024,0.021,0.003).There was no correlation between recurrence of cerebral ischemic stroke and a large area of infarction,cortical infarction,arteriosclerosis and watershed infarction (P values were 0.233,0.945,0.072,0.375).Conclusion Leukoaraiosis,carotid artery plaque and incomplete Willis ring may be risk factors for recurrence of cerebral ischemic stroke.Those signs can provide imaging evidence for secondary prevention of cerebral ischemic stroke.

An analysis of blinding success in a randomised controlled trial of fish oil omega-3 fatty acids

<p><b>INTRODUCTION</b>Incidental reports collected in clinical trials suggest that amongst participants, omega-3 fatty acids derived from fish oil ('omega-3') may be difficult to blind.</p><p><b>MATERIALS AND METHODS</b>We conducted a systematic evaluation of blinding success in a 24-week trial of omega-3 versus an oil-based placebo. Within 1 week of supplement commencement (Week 1), a blinding questionnaire was completed by 131 children enrolled in a trial of omega-3 for the treatment of disruptive behaviour disorders. A version of the questionnaire was also completed by their parents at Week 1, and by the children at the end of supplement administration (Week 24).</p><p><b>RESULTS</b>Participants were unable to differentiate omega-3 from placebo, and accuracy did not improve as a function of: the confidence of guesses, reason for guesses, notice of any change, beliefs about what should change, or time. Child and parent guesses also showed high concordance.</p><p><b>CONCLUSION</b>Taken together, these data provide strong evidence that the identity of omega-3 can be blinded to participants.</p>

Study on steroids of Cacalia tangutica / 中国中药杂志

Seven steroids and two cumarins were isolated from the petroleum ether extract of the specie Cacalia tangutica of the family Compositae which were collected in Minhe county, Qinhai province of China. The structures were identified as Stigmast4-en-3beta, 6beta-diol (1), 24-ethyl-5alpha-cholestane-3beta, 5, 6beta-triol (2), 7beta- methoxy-stigmast-5-en-3beta-ol (3), Schleicherastatin 1 (4), Stigmast-5-en-3beta, 7alpha-diol (5), umbelliferone (6) and hydrangetin (7) by the means of chemical and modern spectroscopic analysis (MS, 1H-NMR, 13C-NMR, DEPT). The compounds 1-5 were isolated from Cacalia tangutica for the first time.

Chemical constituents of Hedysarum polybotrys Hand.-Mazz / 中国中药杂志

Butanedioic acid was isolated from the ethyl alcohol extract of Hedysarum polybotrys. The methylated carboxylic acid was identified by GC-MS method.