Sellersmerrill3822
To present a generalizability assessment method that compares baseline clinical characteristics of trial participants (TP) to potentially eligible (PE) patients as presented in their electronic health record (EHR) data while controlling for clinical setting and recruitment period.
For each clinical trial, a clinical event was defined to identify patients of interest using available EHR data from one clinical setting during the trial's recruitment timeframe. The trial's eligibility criteria were then applied and patients were separated into two mutually exclusive groups (1) TP, which were patients that participated in the trial per trial enrollment data; (2) PE, the remaining patients. The primary outcome was standardized differences in clinical characteristics between TP and PE per trial. A standardized difference was considered prominent if its absolute value was greater than or equal to 0.1. The secondary outcome was the difference in mean propensity scores (PS) between TP and PE per trial, in which thent, but may be a result of other factors such as small sample size or site recruitment strategy. These inconsistent findings suggest eligibility criteria alone are sometimes insufficient in defining a target group to generalize to. With caveats in limited scalability, EHR data quality, and lack of patient perspective on trial participation, this generalizability assessment method that incorporates control for temporality and clinical setting promise to better pinpoint clinical patterns and trial considerations.Different statistical methods include various subjective criteria that can prevent over-testing. However, no unified framework that defines generalized objective criteria for various diseases is available to determine the appropriateness of diagnostic tests recommended by doctors. We present the clinical decision-making framework against over-testing based on modeling the implicit evaluation criteria (CDFO-MIEC). The CDFO-MIEC quantifies the subjective evaluation process using statistics-based methods to identify over-testing. Furthermore, it determines the test's appropriateness with extracted entities obtained via named entity recognition and entity alignment. More specifically, implicit evaluation criteria are defined-namely, the correlation among the diagnostic tests, symptoms, and diseases, confirmation function, and exclusion function. Additionally, four evaluation strategies are implemented by applying statistical methods, including the multi-label k-nearest neighbor and the conditional probability algorithms, to model the implicit evaluation criteria. Finally, they are combined into a classification and regression tree to make the final decision. The CDFO-MIEC also provides interpretability by decision conditions for supporting each clinical decision of over-testing. We tested the CDFO-MIEC on 2,860 clinical texts obtained from a single respiratory medicine department in China with the appropriate confirmation by physicians. The dataset was supplemented with random inappropriate tests. The proposed framework excelled against the best competing text classification methods with a Mean_F1 of 0.9167. This determined whether the appropriate and inappropriate tests were properly classified. The four evaluation strategies captured the features effectively, and they were imperative. Therefore, the proposed CDFO-MIEC is feasible because it exhibits high performance and can prevent over-testing.Varroa destructor is an ectoparasite mite that attacks bees leading to colony disorders worldwide. microRNAs (miRNAs) are key molecules used by eukaryotes to post-transcriptional control of gene expression. Nevertheless, still lack information aboutV. destructor miRNAs and its regulatory networks. Here, we used an integrative strategy to characterize the miRNAs in the V. destructor mite. We identified 310 precursors that give rise to 500 mature miRNAs, which 257 are likely mite-specific elements. miRNAs showed canonical length ranging between 18 and 25 nucleotides and 5' uracil preference. Top 10 elements concentrated over 80% of total miRNA expression, with bantam alone representing ~50%. We also detected non-templated bases in precursor-derived small RNAs, indicative of miRNA post-transcriptional regulatory mechanisms. Finally, we note that conserved miRNAs control similar processes in different organisms, suggesting a conservative role. Altogether, our findings contribute to the better understanding of the mite biology that can assist future studies on varroosis control.
Detection and surveillance of SARS-CoV-2 is of eminent importance, particularly due to the rapid emergence of variants of concern (VOCs). In this study we evaluated if a commercially available quantitative real-time PCR (qRT-PCR) assay can identify SARS-CoV-2 B.1.1.7 lineage samples by a specific Ngene dropout or Ct value shift compared with the S or RdRp gene.
VOC B.1.1.7 and non-B.1.1.7 SARS-CoV-2-positive patient samples were identified via whole-genome sequencing and variant-specific PCR. Confirmed B.1.1.7 (n=48) and non-B.1.1.7 samples (n=58) were analysed using the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay for presence of SARS-CoV-2 S, RdRp and N genes. The N gene coding sequence of SARS-CoV-2 with and without the D3L mutation (specific for B.1.1.7) was cloned into pCR™II-TOPO™ vectors to validate polymorphism-dependent N gene dropout with the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay.
All studied B.1.1.7-positive patient samples showed significantly higher Ct values in qRT-PCR (Δ6-10, N gene dropout on Ct values>29) of N gene than the corresponding values of S (p≤0.0001) and RdRp (p≤0.0001) genes. The assay reliably discriminated B.1.1.7 and non-B.1.1.7 positive samples (area under the curve=1) in a receiver operating characteristic curve analysis. see more Identical Ct value shifts (Δ7-10) were detected in reverse genetic experiments, using isolated plasmids containing N gene coding sequences corresponding to D3 or 3L variants.
An N gene dropout or Ct value shift is shown for B.1.1.7-positive samples in the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay. This approach can be used as a rapid tool for B.1.1.7 detection in single assay high throughput diagnostics.
An N gene dropout or Ct value shift is shown for B.1.1.7-positive samples in the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay. This approach can be used as a rapid tool for B.1.1.7 detection in single assay high throughput diagnostics.
To compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021.
In this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all).
A total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p<0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p<0.0001 and aOR 0.27, p<0.0001, respectively).
The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.
The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.
To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.
In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8days were recruited. A total of 176 eligible patients were randomly assigned (11) to CDCM or placebo. Three rinses daily were performed for 7days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.
The intention-to-treat analysis demonstrated that, over the course of 1day, CDCM was significantly more effective than placebo 4hours after the first dose (p 0.036), with a median percentage (log
copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log
copies/mL; IQR 0-4.19), compared with placebo (3.31 log
copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log
copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis.
This trial supports the relevance of using CDCM on day 1 (4hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.
This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.
To evaluate the molecular mechanisms of ceftazidime/avibactam (CAZ/AVI) resistance in six Klebsiella pneumoniae strains that co-produce K.pneumoniae carbapenemase (KPC)-2 and a novel variant of CMY cephalosporinase in a Chinese hospital.
Antimicrobial susceptibility was determined by broth microdilution. Whole-genome sequencing (WGS) was performed to investigate potential resistance determinants. Plasmid conjugation, electroporation, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) hybridization and cloning experiment were carried out to investigate the resistance plasmids and genes.
A high level of CAZ/AVI resistance was observed in six KPC-Kp strains (MIC 128 mg/L). Five strains were isolated in 2015 and one in 2016, before the approval of CAZ/AVI in China. Sequence analysis indicated that all the strains belonged to sequence type (ST) 11 and uniformly carried a novel CMY AmpC β-lactamase gene, designated bla
. When compared with CMY-2, CMY-172 has a deletion of three consecutive amino acids (K290, V291 and A292) in the R2-loop region and a non-synonymous amino acid substitution at position 346 (N
I).