Search

BackgroundWhile prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron.MethodsWe conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms.ResultsWe enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28).ConclusionsParticipants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste.Trial registrationNCT04610515.

BackgroundThe prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection.MethodsThis was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms.ResultsAmong 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months.ConclusionsWe identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

INTRODUCTION: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. METHODS: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. RESULTS: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). DISCUSSION: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

Objective To explore the application value of automatic nucleic acid extractor combined with vacuum concentrator in forensic DNA extraction. Methods Gradient samples of human peripheral venous blood were collected at 40, 80, 120, 160, 200, 240, 280 and 320 fold dilution. The samples of each gradient were treated with no inhibitor, black oil, rust, fruit acid, tin foil and indigo, respectively. The automatic nucleic acid extractor was used for DNA purification and extraction of the above samples. The extracted DNA eluent （6 μL） was taken for amplification directly, and the rest was concentrated by vacuum concentrator. DNA was amplified and examined using the Investigator 26plex QS kit before and after concentration. Results Only gradient samples treated with fruit acid obtained complete STR typing results at 40 fold dilution. The other 5 methods obtained complete STR typing results at 40-160 fold dilution. The results of STR typing after DNA concentration showed that the average peak height and detection rates of gene loci both increased to a certain extent, but the effect was not obvious. Conclusion The automatic nucleic acid extractor has an efficient inhibitor removal ability and high extracting efficiency of DNA. The vacuum concentrator can concentrate DNA samples to a certain extent. Combining the automatic nucleic acid extractor with the vacuum concentrator can improve the examination success rate of forensic materials.

BackgroundPrior claims analyses suggest that the use of intravenous inotropic therapy for patients hospitalized with heart failure varies substantially by hospital. Whether differences in the clinical characteristics of the patients explain observed differences in the use of inotropic therapy is not known.Methods and resultsWe sought to characterize institutional variation in inotrope use among patients hospitalized with heart failure before and after accounting for clinical factors of patients. Hierarchical generalized linear regression models estimated risk-standardized hospital-level rates of inotrope use within 209 hospitals participating in Get With The Guidelines-Heart Failure (GWTG-HF) registry between 2005 and 2011. The association between risk-standardized rates of inotrope use and clinical outcomes was determined. Overall, an inotropic agent was administered in 7691 of 126 564 (6.1%) heart failure hospitalizations: dobutamine 43%, dopamine 24%, milrinone 17%, or a combination 16%. Patterns of inotrope use were stable during the 7-year study period. Use of inotropes varied significantly between hospitals even after accounting for patient and hospital characteristics (median risk-standardized hospital rate, 5.9%; interquartile range, 3.7%-8.6%; range, 1.3%-32.9%). After adjusting for case-mix and hospital structural differences, model intraclass correlation indicated that 21% of the observed variation in inotrope use was potentially attributable to random hospital effects (ie, institutional preferences). Hospitals with higher risk-standardized inotrope use had modestly longer risk-standardized length of stay (P=0.005) but had no difference in risk-standardized inpatient mortality (P=0.12).ConclusionsUse of intravenous inotropic agents during hospitalization for heart failure varies significantly among US hospitals even after accounting for patient and hospital factors.

After solution treatment at 1300℃ and cold rolling deformation at different reductions, 2205 duplex stainless steel was homogenized at different temperatures for different time intervals. To study the precipitation behavior of σ phase in the steel, the microstructure of specimens was observed by optical microscopy and transmission electron microscopy, and the volume fraction of σ phase in the microstructure was calculated by Image Tool software. The results show that when the steel is homogenized at 950℃, the precipitation time of σ phase is shortened from 30min to 3 rain with the increase of cold rolling reduction from 50% to 85%. As to specimens with a cold rolling reduction of 85%, the volume fraction of σ phase increases from 1.2% to 11.8% when the homogenizing time is prolonged from 3 min to 30 min at 950℃ However, after homogenization for 5 min, the volume fraction of σ phase decreases from 8.9% to 3.6% with the rise of temperature from 875 to 950℃; moreover, when the homogenizing temperature is 975℃, No phase exists in the specimen.

Background The current acute kidney injury (AKI) risk prediction model for patients undergoing percutaneous coronary intervention (PCI) from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) employed regression techniques. This study aimed to evaluate whether models using machine learning techniques could significantly improve AKI risk prediction after PCI. Methods and findings We used the same cohort and candidate variables used to develop the current NCDR CathPCI Registry AKI model, including 947,091 patients who underwent PCI procedures between June 1, 2009, and June 30, 2011. The mean age of these patients was 64.8 years, and 32.8% were women, with a total of 69,826 (7.4%) AKI events. We replicated the current AKI model as the baseline model and compared it with a series of new models. Temporal validation was performed using data from 970,869 patients undergoing PCIs between July 1, 2016, and March 31, 2017, with a mean age of 65.7 years; 31.9% were women, and 72,954 (7.5%) had AKI events. Each model was derived by implementing one of two strategies for preprocessing candidate variables (preselecting and transforming candidate variables or using all candidate variables in their original forms), one of three variable-selection methods (stepwise backward selection, lasso regularization, or permutation-based selection), and one of two methods to model the relationship between variables and outcome (logistic regression or gradient descent boosting). The cohort was divided into different training (70%) and test (30%) sets using 100 different random splits, and the performance of the models was evaluated internally in the test sets. The best model, according to the internal evaluation, was derived by using all available candidate variables in their original form, permutation-based variable selection, and gradient descent boosting. Compared with the baseline model that uses 11 variables, the best model used 13 variables and achieved a significantly better area under the receiver operating characteristic curve (AUC) of 0.752 (95% confidence interval [CI] 0.749-0.754) versus 0.711 (95% CI 0.708-0.714), a significantly better Brier score of 0.0617 (95% CI 0.0615-0.0618) versus 0.0636 (95% CI 0.0634-0.0638), and a better calibration slope of observed versus predicted rate of 1.008 (95% CI 0.988-1.028) versus 1.036 (95% CI 1.015-1.056). The best model also had a significantly wider predictive range (25.3% versus 21.6%, p < 0.001) and was more accurate in stratifying AKI risk for patients. Evaluated on a more contemporary CathPCI cohort (July 1, 2015-March 31, 2017), the best model consistently achieved significantly better performance than the baseline model in AUC (0.785 versus 0.753), Brier score (0.0610 versus 0.0627), calibration slope (1.003 versus 1.062), and predictive range (29.4% versus 26.2%). The current study does not address implementation for risk calculation at the point of care, and potential challenges include the availability and accessibility of the predictors. Conclusions Machine learning techniques and data-driven approaches resulted in improved prediction of AKI risk after PCI. The results support the potential of these techniques for improving risk prediction models and identification of patients who may benefit from risk-mitigation strategies., Author(s): Chenxi Huang 1, Karthik Murugiah 2, Shiwani Mahajan 1, Shu-Xia Li 1, Sanket S. Dhruva 3,4, Julian S. Haimovich 5, Yongfei Wang 1, Wade L. Schulz 1,6, Jeffrey M. [...]

Previous investigations have shown that [approximately equal to] 35% of the 90 tumors analyzed to date contain mutations within the DNA polymerase [beta] (pol [beta]) gene. The existence of pol [beta] mutations in a substantial fraction of human tumors studied suggests a link between DNA pol [beta] and cancer. A DNA pol [beta] variant, in which Lys-289 has been altered to Met, was identified previously in a colorectal carcinoma. The K289M protein was expressed in mouse L cells containing the [lambda] cll mutational target. The [lambda] DNA was packaged and used to infect bacterial cells to obtain the spontaneous mutation frequency. We found that expression of K289M in the mouse cells resulted in a 2.5-fold increase in the mutation frequency. What was most interesting was that expression of K289M in these cells resulted in a 16-fold increase in the frequency of C to G or G to C base substitutions at a specific site within the cll target. By using this cll target sequence, kinetic analysis of the purified K289M protein revealed that it was able to misincorporate dCTP opposite template C and dGTP opposite template G with significantly higher efficiency than the wild-type pol [beta] protein. We provide evidence that misincorporation of nucleotides by K289M results from altered positioning of the DNA within the active site of the enzyme. Our data are consistent with the interpretation that misincorporation of nucleotides resulting from altered DNA positioning by the K289M protein has the potential to result in tumorigenesis or neoplastic progression.

DNA polymerase [Beta] (pol [Beta]) is a 39-kDa protein that functions in DNA repair processes in mammalian cells. As a first step toward understanding mechanisms of polymerase fidelity, we developed a genetic method to identify mammalian pol [Beta] mutator mutants. This screen takes advantage of a microbial genetics assay and the ability of rat pol [Beta] to substitute for Escherichia coli DNA polymerase I in DNA replication in vivo. Using this screen, we identified 13 candidate pol [Beta] mutator routants. Three of the candidate mutator routants were further characterized in vivo and shown to confer an increased spontaneous mutation frequency over that of wild-type pol [Beta] to our bacterial strain. Purification and subsequent analysis of one of our putative mutator proteins, the pol [Beta]-14 protein, showed that it possesses intrinsic mutator activity in four different assays that measure the fidelity of DNA synthesis. Therefore, residue 265, which is altered in pol [Beta]-14 and another of our mutant proteins, pol [Beta]-166, is probably critical for accurate DNA synthesis by pol [Beta]. Thus, our genetic method of screening for pol [Beta] mutator routants is useful in identifying active mammalian DNA polymerase mutants that encode enzymes that catalyze DNA synthesis with altered fidelity compared with the wild-type pol [Beta] enzyme.

Background: New methods such as machine learning techniques have been increasingly used to enhance the performance of risk predictions for clinical decision-making. However, commonly reported performance metrics may not be sufficient to capture the advantages of these newly proposed models for their adoption by health care professionals to improve care. Machine learning models often improve risk estimation for certain subpopulations that may be missed by these metrics.Methods and Results: This article addresses the limitations of commonly reported metrics for performance comparison and proposes additional metrics. Our discussions cover metrics related to overall performance, discrimination, calibration, resolution, reclassification, and model implementation. Models for predicting acute kidney injury after percutaneous coronary intervention are used to illustrate the use of these metrics.Conclusions: We demonstrate that commonly reported metrics may not have sufficient sensitivity to identify improvement of machine learning models and propose the use of a comprehensive list of performance metrics for reporting and comparing clinical risk prediction models. [ABSTRACT FROM AUTHOR]