Brunlanier3841

Mitigating strategies should be adopted when planning the trial. More transparent reporting of planned and actual design features is required.

Investigators must be aware of the risks of recruitment or implementation challenges when considering the use of an SW-CRT design. Mitigating strategies should be adopted when planning the trial. More transparent reporting of planned and actual design features is required.

We systematically evaluated causal language use in systematic reviews of observational studies and explored the relation between language use and the intent of the investigation.

We searched EMBASE, MEDLINE, and Epistemonikos. We randomly selected 199 reviews published in 2019, stratified in a 11 ratio by use and nonuse of the Grading of Recommendations Assessment, Development and Evaluation approach to rating quality of evidence.

Of 199 reviews of observational studies 56.8% had causal intent. Reviews with causal intent were more likely to investigate therapeutic clinical intervention (33.6% vs. 12.8%). Although 78.8% of those with causal intent used causal language in one or more sections of the title, abstract, or main text, only 4.4% consistently used causal language throughout the manuscript, and 21.2% did not use causal language at all. Of reviews without causal intent, 51.2% used causal language somewhere in the manuscript.

Systematic reviews of observational studies sometimes do and sometimes do not have causal intent. Both those are inconsistent in causal language use and often use language inconsistent with the intent. Journal policies would better serve clarity of thinking and appropriateness of inferences by demanding authors clearly specify their intent and consistently use language consistent with that intent.

Systematic reviews of observational studies sometimes do and sometimes do not have causal intent. Both those are inconsistent in causal language use and often use language inconsistent with the intent. Journal policies would better serve clarity of thinking and appropriateness of inferences by demanding authors clearly specify their intent and consistently use language consistent with that intent.

Methods to quantify overdiagnosis of screen detected cancer have been developed, but methods for quantifying overdiagnosis of noncancer conditions (whether symptomatic or asymptomatic) have been lacking. We aimed to develop a methodological framework for quantifying overdiagnosis that may be used for asymptomatic or symptomatic conditions and used gestational diabetes mellitus as an example of how it may be applied.

We identify two earlier definitions for overdiagnosis, a narrower prognosis-based definition and a wider utility-based definition. Building on the central importance of the concepts of prognostic information and clinical utility of a diagnosis, we consider the following questions within a target population, do people found to have a disease using one diagnostic strategy but found not to have the disease using another diagnostic strategy (so called 'additional diagnoses'), have an increased risk of adverse clinical outcomes without treatment (prognosis evidence), and/or a decreased risk of adverse outcomes with treatment (utility evidence)?

Using Causal Directed Acyclic Graphs and fair umpires, we illuminate the relationships between diagnostics strategies and the frequency of overdiagnosis. We then use the example of gestational diabetes mellitus to demonstrate how the Fair Umpire framework may be applied to estimate overdiagnosis.

Our framework may be used to quantify overdiagnosis in noncancer conditions (and in cancer conditions) and to guide further studies on this topic.

Our framework may be used to quantify overdiagnosis in noncancer conditions (and in cancer conditions) and to guide further studies on this topic.DNA helicases function in many types of nucleic acid transactions, and as such, they are vital for genome integrity. Although they are often considered individually, work from many groups demonstrates that these enzymes often genetically and biochemically interact in vivo. Here, we highlight methods to interrogate such interactions among the PIF1 (Pif1 and Rrm3) and RecQ (Hrq1 and Sgs1) family helicases in Saccharomyces cerevisiae. The interactions among these enzymes were investigated in vivo using deletion and inactivation alleles with a gross-chromosomal rearrangement (GCR) assay. Further, wild-type and inactive recombinant proteins were used to determine the effects of the helicases on telomerase activity in vitro. We found that synergistic increases in GCR rates often occur in double vs. single mutants, suggesting that the helicases function in distinct genome integrity pathways. Further, the recombinant helicases can function together in vitro to modulate telomerase activity. Overall, the data suggest that the interactions among the members of these DNA helicase families are multipartite and argue for a comprehensive systems biology approach to fully elucidate the physiological interplay between these enzymes.Mammalian genomes encode over a hundred different helicases, many of which are implicated in the repair of DNA lesions by acting on DNA structures arising during DNA replication, recombination or transcription. Defining the in vivo substrates of such DNA helicases is a major challenge given the large number of helicases in the genome, the breadth of potential substrates in the genome and the degree of genetic pleiotropy among DNA helicases in resolving diverse substrates. Helicases such as WRN, BLM and RECQL5 are implicated in the resolution of error-free recombination events known as sister chromatid exchange events (SCEs). Single cell Strand-seq can be used to map the genomic location of individual SCEs at a resolution that exceeds that of classical cytogenetic techniques by several orders of magnitude. By mapping the genomic locations of SCEs in the absence of different helicases, it should in principle be possible to infer the substrate specificity of specific helicases. Here we describe how the genome can be interrogated for such DNA repair events using single-cell template strand sequencing (Strand-seq) and bioinformatic tools. SCEs and copy-number alterations were mapped to genomic locations at kilobase resolution in haploid KBM7 cells. Strategies, possibilities, and limitations of Strand-seq to study helicase function are illustrated using these cells before and after CRISPR/Cas9 knock out of WRN, BLM and/or RECQL5.G-quadruplex structures (G4s) form readily in DNA and RNA and play diverse roles in gene expression and other processes, and their inappropriate formation and stabilization are linked to human diseases. G4s are inherently long-lived, such that their timely unfolding depends on a suite of DNA and RNA helicase proteins. Biochemical analysis of G4 binding and unfolding by individual helicase proteins is important for establishing their levels of activity, affinity, and specificity for G4s, including individual G4s of varying sequence and structure. Here we describe a set of simple, accessible methods in which electrophoretic mobility shift assays (EMSA) are used to measure the kinetics of G4 binding, dissociation, and unfolding by helicase proteins. We focus on practical considerations and the pitfalls that are most likely to arise when these methods are used to study the activities of helicases on G4s.

The aim was to report the prevalence of diabetes status in patients hospitalized with COVID-19 and assess the association between the glucometabolic status at admission and 90-day mortality.

Consecutive patients hospitalized with COVID-19 were included in the study. All participants included had an HbA

measurement 60days prior to or within 7days after admission. We studied the association between diabetes status, the glycemic gap (difference between admission and habitual status), admission plasma-glucose, and mortality using Cox proportional hazards regression.

Of 674 patients included, 114 (17%) had normal glucose level, 287 (43%) had pre-diabetes, 74 (11%) had new-onset, and 199 (30%) had diagnosed diabetes. No association between diabetes status, plasma-glucose at admission, and mortality was found. Compared to the 2nd quartile (reference) of glycemic-gap, those with the highest glycemic gap had increased mortality (3rd (HR 2.38 [1.29-4.38], p=0.005) and 4th quartile (HR 2.48 [1.37-4.52], p=0.002).

Abnormal glucose metabolism was highly prevalent among patients hospitalized with COVID-19. Diabetes status per se or admission plasma-glucose was not associated with a poorer outcome. However, a high glycemic gap was associated with increased risk of mortality, suggesting that, irrespective of diabetes status, glycemic stress serves as an important prognostic marker for mortality.

Abnormal glucose metabolism was highly prevalent among patients hospitalized with COVID-19. Diabetes status per se or admission plasma-glucose was not associated with a poorer outcome. However, a high glycemic gap was associated with increased risk of mortality, suggesting that, irrespective of diabetes status, glycemic stress serves as an important prognostic marker for mortality.Intermuscular adipose tissue (IMAT) is an ectopic fat depot found beneath the fascia and within the muscles. IMAT modulates muscle insulin sensitivity and triggers local and systemic chronic low-grade inflammation by producing cytokines and chemokines, which underlie the pathogenesis of Type 2 diabetes mellitus (T2DM). Imaging techniques have been increasingly used to non-invasively quantify IMAT in patients with diabetes in research and healthcare settings. In this study, we systematically reviewed the cell of origin and definition of IMAT, and the use of quantitative and functional imaging technology pertinent to the etiology, risk factors, lifestyle modification, and therapeutic treatment of diabetes. The purpose of this article is to provide important insight into the current understanding of IMAT and future prospects of targeting IMAT for T2DM control.

To evaluate the efficacy of 6 Traditional Chinese patent medicines combined with lifestyle modification in the treatment of prediabetes with network meta-analysis.

The randomized controlled trials (RCTs) of Shen qi jiang tang capsule/granule (Shenqi), Tian mai xiao ke tablet (Tianmai), Tian qi capsule (Tianqi), Jin qi jiang tang tablet (Jinqi), Jin li da granule (Jinlida), Tang mai kang granule (Tangmaikang) in the treatment of prediabetes in PubMed, Web of Science, The Cochrane Library, EMbase, China Knowledge Network (CNKI), WanFang and Weipu databases were searched. Three reviewers independently conducted the screening, extracted the data and assessed methodological quality. Data analysis was performed using Rev Man 5.3 and STATA 15.0 software.

A total of 50 RCTs, including 4594 patients, were included. The addition of Shenqi (OR 0.19 [95%CI 0.07, 0.52]) and Jinqi (OR 0.32 [95%CI 0.15, 0.71]) to existing lifestyle modification resulted in significant lower incidence rate of DM compared with none/placor patients with prediabetes. LJI308 Yet direct comparison and further investigation to explore mechanisms are warranted.

For patients with prediabetes, Shenqi + LM was among the most effective in reducing the incidence of diabetes for patients with prediabetes, while Jinlida + LM was among the least effective. Jinqi + LM and Tianqi + LM might be among the most effective, while western oral drugs + LM, Tianmai + LM, Tangmaikang + LM and Placebo + LM might be among the least effective. In addition, Tangmaikang + LM and Jinlida + LM might be among the most effective in reducing HbA1c, while Tianmai + LM, Tangmaikang + LM, Shenqi + LM, Jinlida + LM and Jinqi + LM might be among the most effective in reducing FPG for patients with prediabetes. Yet direct comparison and further investigation to explore mechanisms are warranted.