scholarly journals Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

2021 ◽  
Author(s):  
Xianwu Pang ◽  
Pu Li ◽  
Lifeng Zhang ◽  
Lusheng Que ◽  
Min Dong ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
High Frequency ◽  
Mortality Rates ◽  
Rna Seq ◽  
Related Factors ◽  
High Coverage ◽  
Immunogenic Property ◽  
N Protein ◽  
Mitochondrial Permeability ◽  
Treatment And Prevention

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

scholarly journals Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianwu Pang ◽  
Pu Li ◽  
Lifeng Zhang ◽  
Lusheng Que ◽  
Min Dong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
High Coverage ◽  
Reading Frame ◽  
Treatment And Prevention ◽  
High Prevalence ◽  
Enzyme Mutation ◽  
Editing Enzyme

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

scholarly journals Transcriptome Analysis of Ginkgo biloba L. Leaves across Late Developmental Stages Based on RNA-Seq and Co-Expression Network

Forests ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 315
Author(s):  
Hailin Liu ◽  
Xin Han ◽  
Jue Ruan ◽  
Lian Xu ◽  
Bing He
Keyword(s):  
Ginkgo Biloba ◽  
Leaf Development ◽  
Developmental Stages ◽  
Leaf Growth ◽  
Rna Seq ◽  
Final Size ◽  
Dioecious Species ◽  
Related Factors ◽  
New Genes ◽  
Gene Modules

The final size of plant leaves is strictly controlled by environmental and genetic factors, which coordinate cell expansion and cell cycle activity in space and time; however, the regulatory mechanisms of leaf growth are still poorly understood. Ginkgo biloba is a dioecious species native to China with medicinally and phylogenetically important characteristics, and its fan-shaped leaves are unique in gymnosperms, while the mechanism of G. biloba leaf development remains unclear. In this study we studied the transcriptome of G. biloba leaves at three developmental stages using high-throughput RNA-seq technology. Approximately 4167 differentially expressed genes (DEGs) were obtained, and a total of 12,137 genes were structure optimized together with 732 new genes identified. More than 50 growth-related factors and gene modules were identified based on DEG and Weighted Gene Co-expression Network Analysis. These results could remarkably expand the existing transcriptome resources of G. biloba, and provide references for subsequent analysis of ginkgo leaf development.

scholarly journals Related Factors and Clinical Outcomes of Osteosarcopenia: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 291
Author(s):  
Tatsuro Inoue ◽  
Keisuke Maeda ◽  
Ayano Nagano ◽  
Akio Shimizu ◽  
Junko Ueshima ◽  
...  
Keyword(s):  
Older Adults ◽  
Longitudinal Studies ◽  
Clinical Outcomes ◽  
Daily Living ◽  
Community Dwelling ◽  
Related Factors ◽  
Cross Sectional ◽  
Meta Analyses ◽  
Community Dwelling Older Adults

Osteopenia/osteoporosis and sarcopenia are common geriatric diseases among older adults and harm activities of daily living (ADL) and quality of life (QOL). Osteosarcopenia is a unique syndrome that is a concomitant of both osteopenia/osteoporosis and sarcopenia. This review aimed to summarize the related factors and clinical outcomes of osteosarcopenia to facilitate understanding, evaluation, prevention, treatment, and further research on osteosarcopenia. We searched the literature to include meta-analyses, reviews, and clinical trials. The prevalence of osteosarcopenia among community-dwelling older adults is significantly higher in female (up to 64.3%) compared to male (8–11%). Osteosarcopenia is a risk factor for death, fractures, and falls based on longitudinal studies. However, the associations between osteosarcopenia and many other factors have been derived based on cross-sectional studies, so the causal relationship is not clear. Few studies of osteosarcopenia in hospitals have been conducted. Osteosarcopenia is a new concept and has not yet been fully researched its relationship to clinical outcomes. Longitudinal studies and high-quality interventional studies are warranted in the future.

scholarly journals The Influence of Multidrug-Resistant Bacteria on Clinical Outcomes of Diabetic Foot Ulcers: A Systematic Review

2021 ◽  
Vol 10 (9) ◽  
pp. 1948
Author(s):  
Gianmarco Matta-Gutiérrez ◽  
Esther García-Morales ◽  
Yolanda García-Álvarez ◽  
Francisco Javier Álvaro-Afonso ◽  
Raúl Juan Molines-Barroso ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Diabetic Foot ◽  
Mortality Rates ◽  
Multidrug Resistant ◽  
Healing Time ◽  
Cochrane Library ◽  
Foot Ulcers ◽  
Resistant Organism ◽  
Diabetic Foot Ulcers ◽  
Multidrug Resistant Organisms

Multidrug-resistant organism infections have become important in recent years due to the increased prevalence of diabetic foot ulcers and their possible consequences. This study aimed to systematically review and evaluate ulcer duration, healing time, hospital stay, amputation, and mortality rates in patients with diabetic foot ulcers caused by infection with multidrug-resistant organisms. PubMed, the Cochrane Library, and Web of Science were searched in May 2020 to find observational studies in English about the clinical outcomes of multidrug-resistant organism infection in diabetic foot ulcers. Eight studies met the inclusion criteria, and these studies included 923 patients. The overall methodological quality of the study was moderate. Ulcer duration was described in six studies, and there was no practical association with multidrug-resistant organisms. Two out of three studies reported a longer healing time in multidrug-resistant organism infections than in non-multidrug-resistant organism infections. Clinical outcomes included the duration of hospitalisation, surgeries, amputations, and deaths. Lower limb amputation was the most reported clinical outcome in the included studies, and was more prevalent in the multidrug-resistant organism infections. We concluded that there was not enough evidence that multidrug-resistant organisms hindered the healing of diabetic foot ulcers. In contrast to the clinical outcomes, multidrug-resistant organisms affect both amputation rates and mortality rates.

Abstract 381: Clinical Outcomes Following Transcatheter Aortic Valve Replacement Among US Hospitals

2015 ◽  
Vol 8 (suppl_2) ◽  
Author(s):  
Fenton McCarthy ◽  
Katherine M McDermott ◽  
Vinay Kini ◽  
Dale Kobrin ◽  
Nimesh D Desai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Clinical Outcomes ◽  
Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Mortality Rates ◽  
Transcatheter Aortic Valve ◽  
Cardiovascular Interventions

Background: Transcatheter Aortic Valve Replacement (TAVR) demonstrated excellent outcomes in clinical trials of inoperable/high-risk patients. Subsequent approval by the Food and Drug Administration and National Coverage Determination by the Centers for Medicare and Medicaid Services established unique volume requirements for institutions and physicians to perform TAVR. Diffusion of prior cardiovascular interventions has involved less stringent policies and exhibited significant institutional variation in clinical outcomes. Our objective is to compare risk-standardized procedural outcomes across US hospitals performing TAVR to identify hospitals with outlying post-procedure mortality rates. Methods: All Medicare fee-for-service beneficiaries who underwent TAVR between January 1, 2011 and November 30, 2012 were identified. Thirty-day risk-standardized mortality rates (RSMR) were calculated using the Hospital Compare statistical method, a well-validated hierarchical generalized linear model. Results: Claims were examined from 5044 patients undergoing TAVR at 199 hospitals, with a crude 30-day mortality rate of 5.97%. RSMRs modeled using patient-level predictors varied from 4.5 % to 9.0 % (Figure 1). One hospital had a RSMR statistically lower than the national mean (4.5%, P<0.05), and two hospitals had RSMRs statistically higher than the national mean (8.5% and 6.9%, P<0.05). Conclusions: Clinical outcomes among TAVR hospitals in high-risk/inoperable patients demonstrated very little variability, few outliers, and excellent outcomes comparable to pre-approval clinical trials. This may be the result of the unique policy and regulatory environment governing the CMS coverage determination for TAVR institutions. As TAVR disseminates to additional hospitals and other new cardiovascular interventions are inevitably introduced, risk-standardized outcome comparisons across hospitals may facilitate ongoing surveillance to ensure high quality outcomes at all active centers.

scholarly journals RNA Sequencing-Based Transcriptional Overview of Xerotolerance inCronobacter sakazakiiSP291

2018 ◽  
Vol 85 (3) ◽  
Author(s):  
Shabarinath Srikumar ◽  
Yu Cao ◽  
Qiongqiong Yan ◽  
Koenraad Van Hoorde ◽  
Scott Nguyen ◽  
...  
Keyword(s):  
Infant Formula ◽  
Mortality Rates ◽  
Secondary Response ◽  
Ecological Niches ◽  
Infant Food ◽  
Powdered Infant Formula ◽  
Cronobacter Sakazakii ◽  
Rna Seq ◽  
Production Environment ◽  
Content Type

ABSTRACTCronobacter sakazakiiis a xerotolerant neonatal pathogen epidemiologically linked to powdered infant food formula, often resulting in high mortality rates. Here, we used transcriptome sequencing (RNA-seq) to provide transcriptional insights into the survival ofC. sakazakiiin desiccated conditions. Our RNA-seq data show that about 22% of the totalC. sakazakiigenes were significantly upregulated and 9% were downregulated during desiccation survival. When reverse transcription-quantitative PCR (qRT-PCR) was used to validate the RNA-seq data, we found that the primary desiccation response was gradually downregulated during the tested 4 hours of desiccation, while the secondary response remained constitutively upregulated. The 4-hour desiccation tolerance ofC. sakazakiiwas dependent on the immediate microenvironment surrounding the bacterial cell. The removal of Trypticase soy broth (TSB) salts and the introduction of sterile infant formula residues in the microenvironment enhanced the desiccation survival ofC. sakazakiiSP291. The trehalose biosynthetic pathway encoded byotsAandotsB, a prominent secondary bacterial desiccation response, was highly upregulated in desiccatedC. sakazakii.C. sakazakiiSP291 ΔotsABwas significantly inhibited compared with the isogenic wild type in an 8-hour desiccation survival assay, confirming the physiological importance of trehalose in desiccation survival. Overall, we provide a comprehensive RNA-seq-based transcriptional overview along with confirmation of the phenotypic importance of trehalose metabolism inCronobacter sakazakiiduring desiccation.IMPORTANCECronobacter sakazakiiis a pathogen of importance to neonatal health and is known to persist in dry food matrices, such as powdered infant formula (PIF) and its associated production environment. When infections are reported in neonates, mortality rates can be high. The success of this bacterium in surviving these low-moisture environments suggests thatCronobacterspecies can respond to a variety of environmental signals. Therefore, understanding those signals that aid the persistence of this pathogen in these ecological niches is an important step toward the development of strategies to reduce the risk of contamination of PIF. This research led to the identification of candidate genes that play a role in the persistence of this pathogen in desiccated conditions and, thereby, serve as a model target to design future strategies to mitigate PIF-associated survival ofC. sakazakii.

scholarly journals Clinical outcomes of colistin in combination with either 6-g sulbactam or carbapenems for the treatment of extensively drug-resistant Acinetobacter baumannii pneumonia with high MIC to sulbactam, a prospective cohort study

2019 ◽  
Author(s):  
Chutchawan Ungthammakhun ◽  
Vasin Vasikasin ◽  
Dhitiwat Changpradub
Keyword(s):  
Cohort Study ◽  
Length Of Stay ◽  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Mortality Rates ◽  
P Value ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Abstract Background: Extensively drug-resistant Acinetobacter baumannii (XDRAB) is an important cause of nosocomial pneumonia with limited therapeutic options. Colistin based regimen is recommended treatment. Which drugs should be combined with colistin remains uncertain. The aim of this study was to investigate the clinical outcomes of patients with XDRAB pneumonia who were treated with colistin, combined with either 6-g sulbactam or carbapenems, in the setting of high MIC to sulbactam. Methods: In this prospective cohort study, hospitalized patients diagnosed with XDRAB pneumonia in Phramongkutklao Hospital were enrolled. The primary outcome was the 28-day mortality. Secondary outcomes were 7 and 14-day mortality, length of stay, ventilator days and factors associated with mortality. Results: From 1 July 2016 to 30 September 2017, 192 patients were included; 92 received colistin plus sulbactam and 90 received colistin plus carbapenems. Most of the patients were male diagnosed with ventilator associated pneumonia in medical intensive care unit. Overall mortality rates at 7, 14, 28 days were 24.2%, 37.4%, 53.3%, respectively. Mortality rates did not differ between sulbactam group and carbapenems groups at 7 days (19.6% vs. 28.9%, p-value 0.424, adjusted HR 1.277; 95% CI = 0.702-2.322), 14 days (34.8% vs. 40%, p = 0.658, adjusted HR 1.109; 95% CI = 0.703-1.749) and 28 days (51.1% vs. 55.6%, p = 0.857, adjusted HR 1.038; 95% CI = 0.690-1.562). Length of stay, ICU days and ventilator days did not differ. Complications of treatment including acute kidney injury were not statistically different. Conclusions: In XDRAB pneumonia with high MIC to sulbactam, mortality rates were not statistically significant between colistin plus 6-g sulbactam and colistin plus carbapenems. Keywords: XDR A. baumannii pneumonia, mortality rate, colistin based, sulbactam, carbapenems

Abstract TP19: Clinical Outcomes In Patients With Acute Ischemic Stroke Due To Large Vessel Occlusion In The Modern Era: 2010-2011 Experience With 423 Patients.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Maxim Mokin ◽  
Tareq Kass-Hout ◽  
Omar Kass-Hout ◽  
Erol Veznedaroglu ◽  
Fadi Nahab ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Clinical Outcomes ◽  
Medical Management ◽  
Mortality Rates ◽  
Artery Occlusion ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion

Background and Purpose: Acute ischemic stroke due to large vessel occlusion is associated with a poor prognosis. With no consensus about the best treatment option, various treatment modalities including conservative management, intravenous tissue plasminogen activator, and endovascular approach are currently being used. Methods: Retrospective data including demographic information, baseline NIHSS score, site of occlusion (based on CTA, MRA or angiogram), type of treatment and clinical outcomes were collected from 4 centers in the United States during the period of 2010-2011. Results: A total of 423 were included in final analysis: 175 patients received conservative medical management, 54 patients received intravenous (IV) thrombolysis alone, and 194 patients had endovascular treatment (with or without prior IV tPA). Younger patients were more likely to receive endovascular treatment (p<0.001). There was no statistically significant difference among the sex and co-morbid conditions among the three groups. Proximal middle cerebral artery was the most commonly involved vessel. Strokes due to basilar artery occlusion or internal carotid artery occlusion were associated with worst outcomes in all three groups. Conservative medical management had the lowest rates of symptomatic intracerebral hemorrhage but also the highest mortality rates at 3 months. Patients who received endovascular treatment within the first 3 hrs had better outcome and lower mortality rates as compared to patients with intervention during 3-8 hours or beyond 8 hrs. Conclusions: Our study represents real world experience on the management and outcomes of acute ischemic strokes due to large vessel occlusion. Our results help understand natural history of strokes with large vessel occlusion, as well as modern trends in managing these patients with intravenous and intraarterial treatment approaches.

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