High-Throughput Image-Based Assay for Identifying Hepatocyte Microtubule Disruption.

Disruption of microtubule stability in mammalian cells may lead to genotoxicity and carcinogenesis. The ability to screen for microtubule destabilization or stabilization is therefore a useful and efficient approach to aid in the design of molecules that are safe for human health. In this study, we developed a high-throughput 384-well assay combining immunocytochemistry with high-content imaging to assess microtubule disruption in the metabolically competent human liver cell line: HepaRG.

In Vitro Predictions of Acute Fish Toxicity for Development of Sustainable Crop Protection Products.

New agrochemicals must demonstrate safety to numerous ecological systems, including aquatic systems, and aquatic vertebrate toxicity is typically evaluated by using the in vivo acute fish toxicity (AFT) test. Here, we investigated two alternative in vitro assays using a cell line isolated from rainbow trout () gill tissue: (i) adenosine triphosphate (ATP) luminescence and (ii) cell painting. The former assay measures cytotoxicity, while the latter measures changes in cellular morphology in response to chemical exposure.

Cost-effectiveness Analysis of Colorectal Cancer Screening Strategies Using Active Learning and Monte Carlo Simulation.

Introduction: Detection of colorectal cancer (CRC) in the early stages through available screening tests increases the patient's survival chances. Multimodal screening policies can benefit patients by providing more diverse screening options and balancing the risks and benefits of screening tests. We investigate the cost-effectiveness of a wide variety of multimodal CRC screening policies.

Prediction of the number of COVID-19 confirmed cases based on K-means-LSTM.

COVID-19 is a pandemic disease that began to rapidly spread in the US, with the first case detected on January 19, 2020, in Washington State. March 9, 2020, and then quickly increased with total cases of 25,739 as of April 20, 2020. Although most people with coronavirus 81%, according to the U.

Ion-Selective Membrane-Coated Graphene-Hexagonal Boron Nitride Heterostructures for Field-Effect Ion Sensing.

An intrinsic ion sensitivity exceeding the Nernst-Boltzmann limit and an sp -hybridized carbon structure make graphene a promising channel material for realizing ion-sensitive field-effect transistors with a stable solid-liquid interface under biased conditions in buffered salt solutions. Here, we examine the performance of graphene field-effect transistors coated with ion-selective membranes as a tool to selectively detect changes in concentrations of Ca, K, and Na in individual salt solutions as well as in buffered Locke's solution. Both the shift in the Dirac point and transconductance could be measured as a function of ion concentration with repeatability exceeding 99.

Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity.

Goal: We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans.

Study: We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers. Natural language processing identified the most advanced finding and location (proximal, distal).

Tailoring Surveillance Colonoscopy in Patients With Advanced Adenomas.

Background & Aims: Patients with advanced colorectal adenomas (AAs) are directed to undergo intensive surveillance. However, the benefit derived from surveillance may be outweighed by the risk of death from non-colorectal cancer (CRC) causes, leading to uncertainty on how best to individualize follow-up. The aim of this study was to derive a risk prediction model and risk index that estimate and stratify the risk for non-CRC cancer mortality (NCM) subsequent to diagnosis and removal of AA.

Evaluating the Cost-Effective Use of Follow-Up Colonoscopy Based on Screening Findings and Age.

Introduction: Colorectal cancer (CRC), if not detected early, can be costly and detrimental to one's health. Colonoscopy can identify CRC early as well as prevent the disease. The benefit of screening colonoscopy has been established, but the optimal frequency of follow-up colonoscopy is unknown and may vary based on findings from colonoscopy screening and patient age.

Closed-Loop Intravenous Drug Administration Using Photoplethysmography.

An optically-based injection control system has been developed for preclinical use for an intravenous drug delivery application. Current clinical drug delivery for oncology typically provides for intravenous administration without an awareness of achieved plasma concentration, yet interpatient variability produces consequences ranging from toxicity to ineffectual treatments. We report a closed-loop injection system integrating a pulse-photoplethysmograph to measure the concentration of an injected agent in the circulating blood system using a previously described technique.

Patterns of computed tomography surveillance in survivors of colorectal cancer at Veterans Health Administration facilities.

Background: Annual computed tomography (CT) scans are a component of the current standard of care for the posttreatment surveillance of survivors of colorectal cancer (CRC) after curative-intent resection. The authors conducted a retrospective study with the primary aim of assessing patient, physician, and organizational characteristics associated with the receipt of CT surveillance among veterans.

Methods: The Department of Veterans Affairs Central Cancer Registry was used to identify patients diagnosed with AJCC collaborative stage I to III CRC between 2001 and 2009.

The accuracy and completeness for receipt of colorectal cancer care using Veterans Health Administration administrative data.

Background: The National Comprehensive Cancer Network and the American Society of Clinical Oncology have established guidelines for the treatment and surveillance of colorectal cancer (CRC), respectively. Considering these guidelines, an accurate and efficient method is needed to measure receipt of care.

Methods: The accuracy and completeness of Veterans Health Administration (VA) administrative data were assessed by comparing them with data manually abstracted during the Colorectal Cancer Care Collaborative (C4) quality improvement initiative for 618 patients with stage I-III CRC.

Suppression of the reticuloendothelial system using λ-carrageenan to prolong the circulation of gold nanoparticles.

Aim: Gold nanoparticles are employed for imaging and treatment of surgically inaccessible tumors owing to their inherent optical absorption and ability to extravasate through intravenous distribution. These nanoparticles are cleared from the blood by the reticuloendothelial system (RES) as expected given their size.

Materials & Methods: This study demonstrates the effects of RES blockade through the intravenous administration of λ-carrageenan, resulting in a decrease in the median clearance rate from 18.

Multi-center colonoscopy quality measurement utilizing natural language processing.

Background: An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP).

Methods: From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports.

Clinical trial simulation to evaluate population pharmacokinetics and food effect: capturing abiraterone and nilotinib exposures.

The objectives of this study were to determine (1) the accuracy with which individual patient level exposure can be determined and (2) whether a known food effect can be identified in a trial simulation of a typical population pharmacokinetic trial. Clinical trial simulations were undertaken using NONMEM VII to assess a typical oncology pharmacokinetic trial design. Nine virtual trials for each compound were performed for combinations of different levels of between-occasion variability, number of patients in the trial, and magnitude of a food covariate on oral clearance.

A risk index for advanced neoplasia on the second surveillance colonoscopy in patients with previous adenomatous polyps.

Background: Predicting the risk of advanced colorectal neoplasia on the second surveillance colonoscopy could help tailor surveillance.

Objective: To derive and validate a risk index for advanced neoplasia on the second surveillance colonoscopy.

Design: Retrospective cohort.

A predictive model of longitudinal, patient-specific colonoscopy results.

We suggest a model framework, in which an individual patient's risk for colonic neoplasia varies based on findings from his previous colonoscopies, to predict longitudinal colonoscopy results. The neoplasia natural history model describes progression through four neoplasia development states with patient age. Multiple natural history model parameter sets are assumed to act concurrently on the colon and parameter set prevalence combinations, whose a priori likelihoods are a function of patient sex, provide a basis set for patient-level predictions.

A genetic algorithm based global search strategy for population pharmacokinetic/pharmacodynamic model selection.

The current algorithm for selecting a population pharmacokinetic/pharmacodynamic model is based on the well-established forward addition/backward elimination method. A central strength of this approach is the opportunity for a modeller to continuously examine the data and postulate new hypotheses to explain observed biases. This algorithm has served the modelling community well, but the model selection process has essentially remained unchanged for the last 30 years.

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds.

Population pharmacokinetic analysis of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in adult patients with solid tumors.

Purpose: To identify sources of exposure variability for the tumor growth inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using a population pharmacokinetic analysis.

Methods: A total 67 solid tumor patients at 2 centers were given 1 h infusions of 17-DMAG either as a single dose, daily for 3 days, or daily for 5 days. Blood samples were extensively collected and 17-DMAG plasma concentrations were measured by liquid chromatography/mass spectrometry.

The effect of colonoscopy preparation quality on adenoma detection rates.

Background: Colonoscopy reduces the risk of colorectal cancer mortality by removing precancerous adenomas. The detection rate of subcentimeter (<10 mm) polyps is lower for procedures with inadequate preparation quality.

Objective: To compare the adenoma detection rates of small (6-9 mm) and diminutive (≤ 5 mm) adenomas in patients with poor and fair quality preparations with those with adequate quality preparations.

Provider acceptance, safety, and effectiveness of a computer-based decision tool for colonoscopy preparation.

Purpose: To assess provider acceptance of recommendations by a decision tool that scans the electronic medical record and determines whether sodium phosphate may be taken. In addition, to determine decision tool effects on a composite outcome of colonoscopies canceled, rescheduled, aborted, or repeated sooner than recommended due to preparation (prep) quality; prep quality; colonoscopy duration; and patient satisfaction with and tolerance of the preparation.

Methods: We used 4 alternating 4-week periods to compare the decision tool with usual care for outpatient colonoscopy.

Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration.

Estimation of likely cancer cure using first- and second-order product densities of population balance models.

The objective of chemotherapy is to eradicate all cancerous cells. However, due to the stochastic behavior of cells, the elimination of all cancerous cells must be discussed probabilistically. We hypothesize, and demonstrate in the results, that the mean and standard deviation of a cancer cell population, derived through the probabilistic interpretation of population balance equations, are sufficient to estimate the likelihood of cancer eradication.