FUSE: Improving the estimation and imputation of variant impacts in functional screening.

Deep mutational scanning enables high-throughput functional assessment of genetic variants. While phenotypic measurements from screening assays generally align with clinical outcomes, experimental noise may affect the accuracy of individual variant estimates. We developed the FUSE (functional substitution estimation) pipeline, which leverages measurements collectively within screening assays to improve the estimation of variant impacts.

Summer Cancer Research Experience for High School Students from Historically Marginalized Populations in Kansas City.

The Accelerate Cancer Education (ACE) summer research program at The University of Kansas Cancer Center (KUCC) is a six-week, cancer-focused, summer research experience for high school students from historically marginalized populations in the Kansas City metropolitan area. Cancer affects all populations and continues to be the second leading cause of death in the United States, and a large number of disparities impact racial and ethnic minorities, including increased cancer incidence and mortality. Critically, strategies to bolster diversity, equity, inclusion, and accessibility are needed to address persistent cancer disparities.

What Do Patients Encounter When Searching Online About Meniscal Surgery? An Analysis of Internet Trends.

Background: Many patients use the internet to learn about their orthopaedic conditions and find answers to their common questions. However, the sources and quality of information available to patients regarding meniscal surgery have not been fully evaluated.

Purpose: To determine the most frequently searched questions associated with meniscal surgery based on question type and topic, as well as to assess the website source type and quality.

Indications for Surgery, Activities After Surgery, and Pain Are the Most Commonly Asked Questions in Anterior Cruciate Ligament Injury and Reconstruction.

Purpose: To leverage Google's search algorithms to summarize the most commonly asked questions regarding anterior cruciate ligament (ACL) injuries and surgery.

Methods: Six terms related to ACL tear and/or surgery were searched on a clean-installed Google Chrome browser. The list of questions and their associated websites on the Google search page were extracted after multiple search iterations performed in January of 2022.

Delirium detection using wearable sensors and machine learning in patients with intracerebral hemorrhage.

Objective: Delirium is associated with worse outcomes in patients with stroke and neurocritical illness, but delirium detection in these patients can be challenging with existing screening tools. To address this gap, we aimed to develop and evaluate machine learning models that detect episodes of post-stroke delirium based on data from wearable activity monitors in conjunction with stroke-related clinical features.

Design: Prospective observational cohort study.

Estimating clinical risk in gene regions from population sequencing cohort data.

While pathogenic variants can significantly increase disease risk, it is still challenging to estimate the clinical impact of rare missense variants more generally. Even in genes such as BRCA2 or PALB2, large cohort studies find no significant association between breast cancer and rare missense variants collectively. Here, we introduce REGatta, a method to estimate clinical risk from variants in smaller segments of individual genes.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we substantially improve the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake.

A molecular glue approach to control the half-life of CRISPR-based technologies.

Cas9 is a programmable nuclease that has furnished transformative technologies, including base editors and transcription modulators (e.g., CRISPRi/a), but several applications of these technologies, including therapeutics, mandatorily require precision control of their half-life.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake.

Joint estimation and imputation of variant functional effects using high throughput assay data.

Deep mutational scanning assays enable the functional assessment of variants in high throughput. Phenotypic measurements from these assays are broadly concordant with clinical outcomes but are prone to noise at the individual variant level. We develop a framework to exploit related measurements within and across experimental assays to jointly estimate variant impact.

Estimating clinical risk in gene regions from population sequencing cohort data.

While pathogenic variants significantly increase disease risk in many genes, it is still challenging to estimate the clinical impact of rare missense variants more generally. Even in genes such as or , large cohort studies find no significant association between breast cancer and rare germline missense variants collectively. Here we introduce REGatta, a method to improve the estimation of clinical risk in gene segments.

Associating Social Determinants of Health With PROMIS CAT Scores and Health Care Utilization After ACL Reconstruction.

Background: The term "social determinants of health" (SDOH) refers to social and economic factors that influence a patient's health status. The effect of SDOH on the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive test (CAT) scores and postoperative resource utilization in patients with anterior cruciate ligament reconstruction (ACLR) have yet to be thoroughly studied.

Purpose: To investigate the impact SDOH have on PROMIS CAT outcomes and postoperative resource utilization in patients with ACLR.

Informing variant assessment using structured evidence from prior classifications (PS1, PM5, and PVS1 sequence variant interpretation criteria).

Purpose: This study aimed to explore whether evidence of pathogenicity from prior variant classifications in ClinVar could be used to inform variant interpretation using the American College of Medical Genetics and Genomics/Association for Molecular Pathology clinical guidelines.

Methods: We identified distinct single-nucleotide variants (SNVs) that are either similar in location or in functional consequence to pathogenic variants in ClinVar and analyzed evidence in support of pathogenicity using 3 interpretation criteria.

Results: Thousands of variants, including many in clinically actionable disease genes (American College of Medical Genetics and Genomics secondary findings v3.

Causes and predictors of failed same-day home discharge following primary hip and knee total joint arthroplasty: a Canadian perspective.

Purpose: Same-day home (SDH) discharge in total joint arthroplasty (TJA) has increased in popularity in recent years. The objective of this study was to evaluate the causes and predictors of failed discharges in planned SDH patients.

Methods: A consecutive cohort of patients who underwent total knee (TKA) or total hip arthroplasty (THA) that were scheduled for SDH discharge between 01 April 2019 and 31 March 2021 were retrospectively reviewed.

Peptide fusion improves prime editing efficiency.

Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites.

Publications search optimization: Comparison of a homegrown-API approach versus manual publication searches at an NCI designated cancer center.

One measure of research productivity within the University of Kansas Cancer Center (KU Cancer Center) is peer-reviewed publications. Considerable effort goes into searching, capturing, reviewing, storing, and reporting cancer-relevant publications. Traditionally, the method of gathering relevant information to the publications is done manually.

World trends in sugar-sweetened beverage and dietary sugar intakes in children and adolescents: a systematic review.

Objective: To provide a systematic overview of world dietary sugar and sugar-sweetened beverage (SSB) intake trends in children and adolescents.

Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched through January 2019 to identify longitudinal follow-up studies with time-trend data and repeated cross-sectional studies.

Data Extraction: Data from studies reporting ≥ 2 measurements (sugars, SSB, or sweets/candy) over ≥ 2 years and included ≥ 20 healthy, normal- or overweight children or adolescents aged 1-19 years.

Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics.

The adenosine analogue remdesivir has emerged as a front-line antiviral treatment for SARS-CoV-2, with preliminary evidence that it reduces the duration and severity of illness.Prior clinical studies have identified adverse events, and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments, yet little is known about the specific genetic pathways involved in cellular remdesivir metabolism and cytotoxicity. Through genome-wide CRISPR-Cas9 screening and RNA sequencing, we show that remdesivir treatment leads to a repression of mitochondrial respiratory activity, and we identify five genes whose loss significantly reduces remdesivir cytotoxicity.

General fluid/inductive reasoning battery for a high-ability population.

The validity of studies investigating interventions to enhance fluid intelligence (Gf) depends on the adequacy of the Gf measures administered. Such studies have yielded mixed results, with a suggestion that Gf measurement issues may be partly responsible. The purpose of this study was to develop a Gf test battery comprising tests meeting the following criteria: (a) strong construct validity evidence, based on prior research; (b) reliable and sensitive to change; (c) varying in item types and content; (d) producing parallel tests, so that pretest-posttest comparisons could be made; (e) appropriate time limits; (f) unidimensional, to facilitate interpretation; and (g) appropriate in difficulty for a high-ability population, to detect change.

Topological inversions in coalescing granular media control fluid-flow regimes.

Sintering-or coalescence-of viscous droplets is an essential process in many natural and industrial scenarios. Current physical models of the dynamics of sintering are limited by the lack of an explicit account of the evolution of microstructural geometry. Here, we use high-speed time-resolved x-ray tomography to image the evolving geometry of a sintering system of viscous droplets, and use lattice Boltzmann simulations of creeping fluid flow through the reconstructed pore space to determine its permeability.

Detergency and Its Implications for Oil Emulsion Sieving and Separation.

Separating petroleum hydrocarbons from water is an important problem to address in order to mitigate the disastrous effects of hydrocarbons on aquatic ecosystems. A rational approach to address the problem of marine oil-water separation is to disperse the oil with the aid of surfactants in order to minimize the formation of large slicks at the water surface and to maximize the oil-water interfacial area. Here we investigate the fundamental wetting and transport behavior of such surfactant-stabilized droplets and the flow conditions necessary to perform sieving and separation of these stabilized emulsions.

Comparison of three-dimensional analysis and stereological techniques for quantifying lithium-ion battery electrode microstructures.

Lithium-ion battery performance is intrinsically linked to electrode microstructure. Quantitative measurement of key structural parameters of lithium-ion battery electrode microstructures will enable optimization as well as motivate systematic numerical studies for the improvement of battery performance. With the rapid development of 3-D imaging techniques, quantitative assessment of 3-D microstructures from 2-D image sections by stereological methods appears outmoded; however, in spite of the proliferation of tomographic imaging techniques, it remains significantly easier to obtain two-dimensional (2-D) data sets.

Repeated crack healing in MAX-phase ceramics revealed by 4D in situ synchrotron X-ray tomographic microscopy.

MAX phase materials are emerging as attractive engineering materials in applications where the material is exposed to severe thermal and mechanical conditions in an oxidative environment. The Ti2AlC MAX phase possesses attractive thermomechanical properties even beyond a temperature of 1000 K. An attractive feature of this material is its capacity for the autonomous healing of cracks when operating at high temperatures.

Transgranular liquation cracking of grains in the semi-solid state.

Grain refinement via semi-solid deformation is desired to obtain superior mechanical properties of cast components. Using quantitative in situ synchrotron X-ray tomographic microscopy, we show an additional mechanism for the reduction of grain size, via liquation assisted transgranular cracking of semi-solid globular microstructures. Here we perform localized indentation of Al-15wt.

Integrated approach to the data processing of four-dimensional datasets from phase-contrast x-ray tomography.

Phase contrast X-ray tomography (PCT) enables the study of systems consisting of elements with similar atomic numbers. Processing datasets acquired using PCT is nontrivial because of the low-pass characteristics of the commonly used single-image phase retrieval algorithm. In this study, we introduce an image processing methodology that simultaneously utilizes both phase and attenuation components of an image obtained at a single detector distance.