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Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (<11.2% coefficient of variation). [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has forced many universities to move to online learning to sustain students' education. Today's Students are digital natives. They grew up with digital technologies and have different learning styles, new attitude to the learning process and higher requirements for teaching and learning. Indeed, there is a need to develop new e-learning models that transform education to sustain goals and achieve education's objectives. Modern pedagogical paradigms and trends in education, reinforced by the use of ICT, create prerequisites for use of new approaches and techniques in order to implement active learning. Gamification is one of these trends as applying gamification in a non-gaming environment motivates students and also keeps them engaged in learning. The purpose of this research is to empirically investigate gamification intention to use in E-learning through student attitude in the Egyptian Private Higher Education Institutions (HIEs). This study proposes to integrate the personal characteristics including the dimensions (computer anxiety, enjoyment, self-efficacy) which extends the Technology Acceptance Model (TAM) including dimensions (Perceived usefulness, perceived ease of use). The objectives of this research are: to examine how gamification affects intention to use in E-learning, to identify how gamification affects student's attitude, to investigate how student's attitude affects intention to use gamification. Data in this study came from a survey of 4.3 acceptable responses. the results were analysed employing by Structural Equation Modeling technique (SEM) using Analysis Moment of Structures (AMOS) software. The main conclusions drawn from this study are: the direct effect between gamifications and intention to use gamification in E-learning is statistically significant, the direct effect between gamification and student's attitude towards gamification is statistically significant, the direct effect between student's attitude towards gamification and intention to use gamification in E-learning is statistically significant, and finally, student's attitude mediates the relationship between gamification and intention to use Egyptian higher education institutions. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACi) are cancer therapeutics that operate at the epigenetic level and which have recently gained wide attention. However, the applications of HDACi are generally hindered by their poor physicochemical characteristics and unfavorable pharmacokinetic profile. Inspired by the approved nanomedicine-based drugs in the market, nanocarriers could provide a resort to circumvent the limitations imposed by HDACi. Enhanced tumor targeting, improved cellular uptake and reduced toxicity are major advantages offered by HDACi-loaded nanoparticles. More importantly, site-specific drug delivery can be achieved via engineered stimuli-responsive nanosystems. In this review we elucidate the anticancer mechanisms of HDACi and their structure–activity relationships, with a special focus on their nanomedicine-based delivery, different drug loading concepts and their implications. [ABSTRACT FROM AUTHOR]

Background: Greater purpose in life is associated with lower rates of certain chronic diseases. Whether purpose in life can protect against development of prediabetes or type 2 diabetes is unknown.Purpose: To examine the association between purpose in life and blood glucose control among adults ≥50 years.Methods: We conducted a longitudinal cohort study of 3,907 participants of the Health and Retirement Study who at baseline did not have type 2 diabetes or prediabetes. Baseline purpose in life was measured using the Ryff and Keyes' Scales of Psychological Well-Being and grouped into tertiles (high, medium, and low). We used multivariable linear regression to examine the association between baseline purpose in life and HbA1c over 4 years. Multivariable logistic regression was used to examine the association between baseline purpose and incident prediabetes or type 2 diabetes over the same period.Results: After adjusting for sociodemographic factors, body mass index, physical activity, and physical and mental health factors, HbA1c was 0.07 percentage points lower among participants with high purpose than those with low purpose (95% confidence interval [CI] -0.12 to -0.02; p = .011). Participants with high purpose had lower odds of developing prediabetes or type 2 diabetes than those with low purpose (adjusted odds ratio 0.78; 95% CI 0.62 to 0.98; p = .037).Conclusions: Among older adults, greater purpose in life is associated with a lower incidence of prediabetes or type 2 diabetes. Strategies to promote greater purpose in life should be tested as a part of type 2 diabetes prevention efforts. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The purpose of this paper was to review studies of behavioral economic interventions (financial incentives, choice architecture modifications, or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk patients or improve self-management among patients with T2DM.Recent Findings: We found 15 studies that used varied study designs and outcomes to test behavioral economic interventions in clinical, workplace, or health plan settings. Of four studies that focused on prevention of T2DM, two found that financial incentives increased weight loss and completion of a fasting blood glucose test, and two choice architecture modifications had mixed effects in encouraging completion of tests to screen for T2DM. Of 11 studies that focused on improving self-management of T2DM, four of six tests of financial incentives demonstrated increased engagement in recommended care processes or improved biometric measures, and three of five tests of choice architecture modifications found improvements in self-management behaviors. Though few studies have tested behavioral economic interventions for prevention or treatment of T2DM, those that have suggested such approaches have the potential to improve patient behaviors and such approaches should be tested more broadly. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment of prediabetes and type 2 diabetes mellitus (T2DM) can prevent future health problems, yet many individuals with these conditions are undiagnosed. This could be due, in part, to primary care physicians' (PCP) screening practices, about which little is known. The objectives of this study were to identify factors that influence PCPs' decisions to screen patients for T2DM and to characterize their interpretation and communication of screening test results to patients. Methods: We conducted semi-structured chart-stimulated recall interviews with 20 University of Michigan Health System (UMHS) primary care physicians. PCPs were asked about their recent decisions to screen or not screen 134 purposively sampled non-diabetic patients who met American Diabetes Association criteria for screening for T2DM. Interviews were audio-recorded, transcribed, and analyzed using qualitative directed content analysis. Data on patient demographic characteristics and comorbidities were abstracted from the electronic health record. Results: The most common reasons PCPs gave for not screening 63 patients for T2DM were knowledge of a previously normal screening test (49%) and a visit for reasons other than a health maintenance examination (48%). The most common reasons PCPs gave for screening 71 patients for T2DM were knowledge of a previously abnormal screening test (49%), and patients' weight (42%) and age (38%). PCPs correctly interpreted 89% of screening test results and communicated 95% of test results to patients. Among 24 patients found to have prediabetes, PCPs usually (58%) recommended weight loss and increased physical activity but never recommended participation in a Diabetes Prevention Program or use of metformin. Conclusions: Previous screening test results, visit types, and patients' weight and age influenced PCPs' decisions to screen for T2DM. When patients were screened, test results were generally correctly interpreted and consistently communicated. Recommendations to patients with prediabetes could better reflect evidence-based strategies to prevent T2DM. [ABSTRACT FROM AUTHOR]

Purpose Of Review: This study aims to summarize the recent peer-reviewed literature on workplace interventions for prevention of type 2 diabetes mellitus (T2DM), including studies that translate the Diabetes Prevention Program (DPP) curriculum to workplace settings (n = 10) and those that use different intervention approaches to achieve the specific objective of T2DM prevention among employees (n = 3).Recent Findings: Weight reduction was achieved through workplace interventions to prevent T2DM, though such interventions varied substantially in their effectiveness. The greatest weight loss was reported among intensive lifestyle interventions (i.e., at least 4 months in duration) that implemented the structured DPP curriculum (n = 3). Weight reduction was minimal among less intensive interventions, including those that substantially modified the DPP curriculum (n = 2) and those that used non-DPP intervention approaches to prevent T2DM (n = 3). Most studies (n = 12) reported increased levels of physical activity following the intervention. Implementation of the DPP in workplaces may be an effective strategy to prevent T2DM among employees. [ABSTRACT FROM AUTHOR]

The article discusses the resident-led implementation of National Diabetes Prevention Program (NDPP) of Centers for Disease Control and Prevention (CDC) at a resident community clinic in the Fall of 2013. Topics discussed include pilot grant received through "Fostering Innovation Grant" program, and work to expand NDPP to other primary care sites of University Michigan Health System (UMHS) with Adult Diabetes Education team under Division of Metabolism, Endocrinology and Diabetes (MEND).

Motivation: Pre-mRNA cleavage and polyadenylation are essential steps for 3′-end maturation and subsequent stability and degradation of mRNAs. This process is highly controlled by cis-regulatory elements surrounding the cleavage/polyadenylation sites (polyA sites), which are frequently constrained by sequence content and position. More than 50% of human transcripts have multiple functional polyA sites, and the specific use of alternative polyA sites (APA) results in isoforms with variable 3′-untranslated regions, thus potentially affecting gene regulation. Elucidating the regulatory mechanisms underlying differential polyA preferences in multiple cell types has been hindered both by the lack of suitable data on the precise location of cleavage sites, as well as of appropriate tests for determining APAs with significant differences across multiple libraries.Results: We applied a tailored paired-end RNA-seq protocol to specifically probe the position of polyA sites in three human adult tissue types. We specified a linear-effects regression model to identify tissue-specific biases indicating regulated APA; the significance of differences between tissue types was assessed by an appropriately designed permutation test. This combination allowed to identify highly specific subsets of APA events in the individual tissue types. Predictive models successfully classified constitutive polyA sites from a biologically relevant background (auROC = 99.6%), as well as tissue-specific regulated sets from each other. We found that the main cis-regulatory elements described for polyadenylation are a strong, and highly informative, hallmark for constitutive sites only. Tissue-specific regulated sites were found to contain other regulatory motifs, with the canonical polyadenylation signal being nearly absent at brain-specific polyA sites. Together, our results contribute to the understanding of the diversity of post-transcriptional gene regulation.Availability: Raw data are deposited on SRA, accession numbers: brain SRX208132, kidney SRX208087 and liver SRX208134. Processed datasets as well as model code are published on our website: http://www.genome.duke.edu/labs/ohler/research/UTR/Contact: uwe.ohler@duke.edu [ABSTRACT FROM AUTHOR]