The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank.

Large-scale genome-wide association studies (GWAS) strongly suggest that most traits and diseases have a polygenic component. This observation has motivated the development of disease-specific "polygenic scores (PGS)" that are weighted sums of the effects of disease-associated variants identified from GWAS that correlate with an individual's likelihood of expressing a specific phenotype. Although most GWAS have been pursued on disease traits, leading to the creation of refined "Polygenic Risk Scores" (PRS) that quantify risk to diseases, many GWAS have also been pursued on extreme human longevity, general fitness, health span, and other health-positive traits.

A CRISPR-enhanced metagenomic NGS test to improve pandemic preparedness.

The lack of preparedness for detecting and responding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen (i.e., COVID-19) has caused enormous harm to public health and the economy.

A conditional RNA Pol II mono-promoter drives HIV-inducible, CRISPR-mediated cyclin T1 suppression and HIV inhibition.

Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) targeted to HIV proviral DNA has shown excision of HIV from infected cells. However, CRISPR-based HIV excision is vulnerable to viral escape. Targeting cellular co-factors provides an attractive yet risky alternative to render viral escape irrelevant.

Interrogating the Human Diplome: Computational Methods, Emerging Applications, and Challenges.

Human DNA sequencing protocols have revolutionized human biology, biomedical science, and clinical practice, but still have very important limitations. One limitation is that most protocols do not separate or assemble (i.e.

Nonalcoholic fatty liver disease risk and histologic severity are associated with genetic polymorphisms in children.

Background And Aims: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity.

Accommodating Serial Correlation and Sequential Design Elements in Personalized Studies and Aggregated Personalized Studies.

Single subject, or 'N-of-1,' studies are receiving a great deal of attention from both theoretical and applied researchers. This is consistent with the growing acceptance of 'personalized' approaches to health care and the need to prove that personalized interventions tailored to an individual's likely unique physiological profile and other characteristics work as they should. In fact, the preferred way of referring to N-of-1 studies in contemporary settings is as 'personalized studies.

Cross-Species and Human Inter-Tissue Network Analysis of Genes Implicated in Longevity and Aging Reveal Strong Support for Nutrient Sensing.

Intensive research efforts have been undertaken to slow human aging and therefore potentially delay the onset of age-related diseases. These efforts have generated an enormous amount of high-throughput data covering different levels in the physiologic hierarchy, e.g.

Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities.

A 25-y longitudinal dolphin cohort supports that long-lived individuals in same environment exhibit variation in aging rates.

While it is believed that humans age at different rates, a lack of robust longitudinal human studies using consensus biomarkers meant to capture aging rates has hindered an understanding of the degree to which individuals vary in their rates of aging. Because bottlenose dolphins are long-lived mammals that develop comorbidities of aging similar to humans, we analyzed data from a well-controlled, 25-y longitudinal cohort of 144 US Navy dolphins housed in the same oceanic environment. Our analysis focused on 44 clinically relevant hematologic and clinical chemistry measures recorded during routine blood draws throughout the dolphins' lifetimes.

Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets.

To identify features in the genome of the SARS-CoV-2 pathogen responsible for the COVID-19 pandemic that may contribute to its viral replication, host pathogenicity, and vulnerabilities, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes. Our analyses suggest the presence of unique sequence signatures in the 3'-untranslated region (UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2, SARS-CoV, as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection.

Strategies for Testing Intervention Matching Schemes in Cancer.

Personalized medicine, or the tailoring of health interventions to an individual's nuanced and often unique genetic, biochemical, physiological, behavioral, and/or exposure profile, is seen by many as a biological necessity given the great heterogeneity of pathogenic processes underlying most diseases. However, testing and ultimately proving the benefit of strategies or algorithms connecting the mechanisms of action of specific interventions to patient pathophysiological profiles (referred to here as "intervention matching schemes" (IMS)) is complex for many reasons. We argue that IMS are likely to be pervasive, if not ubiquitous, in future health care, but raise important questions about their broad deployment and the contexts within which their utility can be proven.

Guardant360 Circulating Tumor DNA Assay Is Concordant with FoundationOne Next-Generation Sequencing in Detecting Actionable Driver Mutations in Anti-EGFR Naive Metastatic Colorectal Cancer.

Background: Direct comparisons between Guardant360 (G360) circulating tumor DNA (ctDNA) and FoundationOne (F1) tumor biopsy genomic profiling in metastatic colorectal cancer (mCRC) are limited. We aim to assess the concordance across overlapping genes tested in both F1 and G360 in patients with mCRC.

Materials And Methods: We retrospectively analyzed 75 patients with mCRC who underwent G360 and F1 testing.

Power and Design Issues in Crossover-Based N-Of-1 Clinical Trials with Fixed Data Collection Periods.

"N-of-1," or single subject, clinical trials seek to determine if an intervention strategy is more efficacious for an individual than an alternative based on an objective, empirical, and controlled study. The design of such trials is typically rooted in a simple crossover strategy with multiple intervention response evaluation periods. The effect of serial correlation between measurements, the number of evaluation periods, the use of washout periods, heteroscedasticity (i.

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Aims: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA in those with long duration (> 5 years) Type 1 diabetes.

Salt Induced Structural Collapse, Swelling, and Signature of Aggregation of Two ssDNA Strands: Insights from Molecular Dynamics Simulation.

Molecular dynamics simulations elucidate the structural collapse shown by two ssDNAs of the same base sequence in the presence of either Na or Mg, starting from in vivo ionic concentration to higher concentrations. Initially, an increase in ion concentration facilitates the structural distortion of individual ssDNA and helps to bring them close, and for this, Mg is better than Na. However, further addition of ions leads to structural reswelling of the DNA strands and inhibits their proximity.

Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation.

Background: Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL.

Rectal Cancer Survivors' Participation in Productive Activities.

Context: Rectal cancer and its treatment impair survivors' productivity.

Objective: To assess determinants of market and nonmarket employment, job search, volunteering, and homemaking among survivors five years or longer after diagnosis.

Design: We mailed questionnaires to 1063 survivors who were members of Kaiser Permanente (Northern California, Northwest) during 2010 and 2011.

Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations.

Background: Enhanced recovery following surgery can be achieved through the introduction of evidence-based perioperative maneuvers. This review aims to present a consensus for optimal perioperative management of patients undergoing breast reconstructive surgery and to provide evidence-based recommendations for an enhanced perioperative protocol.

Methods: A systematic review of meta-analyses, randomized controlled trials, and large prospective cohorts was conducted for each protocol element.

Participation in Activities Associated With Quality of Life for Long-Term Survivors of Rectal Cancer.

Context: Cancer patients' participation in social, recreational, and civic activities is strongly associated with quality of life (QOL), but these activities are not well integrated into cancer survivorship research or interventions.

Objective: Test the hypothesis that for long-term (≥ 5 years) survivors of rectal cancer, clinical factors (type of surgery and bowel function) are associated with long-term participation in activities and that participation in activities is associated with long-term QOL.

Design: Observational study with longitudinal and cross-sectional components.