Characteristics of patients with liver tumors deemed ineligible for enrollment on Children's Oncology Group trial AHEP1531: An opportunity to expand inclusion criteria and improve outcome.

Background: Specific patients with hepatoblastoma (HB) and hepatocellular carcinoma (HCC) do not meet eligibility criteria for Children's Oncology Group (COG) trials, limiting an understanding of how comorbidities affect the outcome. We define such a population for future-focused care improvements.

Methods: A questionnaire was sent to COG institutional principal investigators to obtain anonymized data regarding patients with a liver tumor diagnosis not enrolled on AHEP1531 due to ineligibility by trial criteria or other reasons (excluding parent/patient preference).

Development of an Apple Snack Enriched with Probiotic : Evaluation of the Refractance Window Drying Process on Cell Viability.

The objective of this study was to develop a dried apple snack enriched with probiotics, evaluate its viability using Refractance Window (RW) drying, and compare it with conventional hot air drying (CD) and freeze-drying (FD). Apple slices were impregnated with and dried at 45 °C using RW and CD and FD. Total polyphenol content (TPC), color (∆E*), texture, and viable cell count were measured, and samples were stored for 28 days at 4 °C.

Application of CO-Laser Micro-Perforation Technology to Freeze-Drying Whole Strawberry (.): Effect on Primary Drying Time and Fruit Quality.

Freeze-drying (FD) processing preserves foods by combining the most effective traditional technologies. FD conserves the structure, shape, freshness, nutritional/bioactive value, color, and aroma at levels similar to or better than those of refrigerated and frozen foods while delivering the shelf-stable convenience of canned/hot-air-dehydrated foods. The mass transfer rate is the essential factor that can slow down the FD process, resulting in an excessive primary drying time and high energy consumption.

Effect of CO Laser Microperforation Pretreatment on the Dehydration of Apple Slices during Refractive Window Drying.

This research studied the use of CO LASER microperforation as a pretreatment for the refractive window (RW) drying of apple slices with respect to total polyphenol content (TPC), antioxidant capacity, color Δ, and product stability under accelerated storage. For this purpose, the processing variables assessed were pore size (200-600 µm), pore density (9-25 pores/cm), and drying temperature (70-90 °C). As baseline criteria, a comparison with respect to the control without microperforations and samples subjected to conventional tunnel and lyophilization were also considered.

Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment.

Introduction: Epigenetic stimuli induce beneficial or detrimental changes in gene expression, and consequently, phenotype. Some of these phenotypes can manifest across the lifespan-and even in subsequent generations. Here, we used a mouse model of vascular cognitive impairment and dementia (VCID) to determine whether epigenetically induced resilience to specific dementia-related phenotypes is heritable by first-generation progeny.

Transmission of SARS-CoV-2 considering shared chairs in outpatient dialysis: a real-world case-control study.

Background: SARS-CoV-2 can remain transiently viable on surfaces. We examined if use of shared chairs in outpatient hemodialysis associates with a risk for indirect patient-to-patient transmission of SARS-CoV-2.

Methods: We used data from adults treated at 2,600 hemodialysis facilities in United States between February 1st and June 8th, 2020.

Machine learning directed interventions associate with decreased hospitalization rates in hemodialysis patients.

Background: An integrated kidney disease company uses machine learning (ML) models that predict the 12-month risk of an outpatient hemodialysis (HD) patient having multiple hospitalizations to assist with directing personalized interdisciplinary interventions in a Dialysis Hospitalization Reduction Program (DHRP). We investigated the impact of risk directed interventions in the DHRP on clinic-wide hospitalization rates.

Methods: We compared the hospital admission and day rates per-patient-year (ppy) from all hemodialysis patients in 54 DHRP and 54 control clinics identified by propensity score matching at baseline in 2015 and at the end of the pilot in 2018.

Transmission of SARS-CoV-2 Considering Shared Chairs in Outpatient Dialysis: A Real-World Case-Control Study.

Background: SARS-CoV-2 is primarily transmitted through aerosolized droplets; however, the virus can remain transiently viable on surfaces.

Objective: We examined transmission within hemodialysis facilities, with a specific focus on the possibility of indirect patient-to-patient transmission through shared dialysis chairs.

Design: We used real-world data from hemodialysis patients treated between February 1 and June 8 , 2020 to perform a case-control study matching each SARS-CoV-2 positive patient (case) to a non-SARS-CoV-2 patient (control) in the same dialysis shift and traced back 14 days to capture possible exposure from chairs sat in by SARS-CoV-2 patients.

Machine Learning for Prediction of Patients on Hemodialysis with an Undetected SARS-CoV-2 Infection.

Background: We developed a machine learning (ML) model that predicts the risk of a patient on hemodialysis (HD) having an undetected SARS-CoV-2 infection that is identified after the following ≥3 days.

Methods: As part of a healthcare operations effort, we used patient data from a national network of dialysis clinics (February-September 2020) to develop an ML model (XGBoost) that uses 81 variables to predict the likelihood of an adult patient on HD having an undetected SARS-CoV-2 infection that is identified in the subsequent ≥3 days. We used a 60%:20%:20% randomized split of COVID-19-positive samples for the training, validation, and testing datasets.

Intra- and intergenerational changes in the cortical DNA methylome in response to therapeutic intermittent hypoxia in mice.

Recent evidence from our laboratory documents functional resilience to retinal ischemic injury in untreated mice derived from parents exposed to repetitive hypoxic conditioning (RHC) before breeding. To begin to understand the epigenetic basis of this intergenerational protection, we used methylated DNA immunoprecipitation and sequencing to identify genes with differentially methylated promoters (DMGPs) in the prefrontal cortex of mice treated directly with the same RHC stimulus (F0-RHC) and in the prefrontal cortex of their untreated F1-generation offspring (F1-*RHC). Subsequent bioinformatic analyses provided key mechanistic insights into how changes in gene expression secondary to promoter hypo- and hypermethylation might afford such protection within and across generations.

Intermittent streptozotocin administration induces behavioral and pathological features relevant to Alzheimer's disease and vascular dementia.

Rationale: Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, on vascular and inflammatory changes within the brain.

Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery.

MicroRNAs are emerging as promising biomarkers for diagnosis of various diseases. Notably, cerebrospinal fluid (CSF) contains microRNAs that may serve as biomarkers for neurological diseases. However, there has been a lack of consistent findings among CSF microRNAs studies.

miR-186 is decreased in aged brain and suppresses BACE1 expression.

Accumulation of amyloid β (Aβ) in the brain is a key pathological hallmark of Alzheimer's disease (AD). Because aging is the most prominent risk factor for AD, understanding the molecular changes during aging is likely to provide critical insights into AD pathogenesis. However, studies on the role of miRNAs in aging and AD pathogenesis have only recently been initiated.

An Exploration of Family and Juvenile Justice Systems to Reduce Youth HIV/STI Risk.

Using in-depth interviews with 20 probation youth (60% female; 35% white; 30% Hispanic; mean age 15years, range=13-17), their caregivers (100% female; mean age 44years, range=34-71) and 12 female probation officers (100% white; mean age 46years, range=34-57), we explored how family and probation systems exacerbate or mitigate sexual risk. We conducted thematic analyses of interviews, comparing narratives of families of sexually risky (9) versus non-sexually risky (11) youth. Family functioning differed by youth sexual risk behavior around quality of relationships, communication, and limit-setting and monitoring.

Tyrosine urea muscarinic acetylcholine receptor antagonists: achiral quaternary ammonium groups.

Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers.

How students' achievement goals shape their beliefs about effective teaching: a 'build-a-professor' study.

Background: Which instructor qualities do students consider most important? The answer likely depends on the student. This study attempted to trace beliefs about the most essential instructor qualities to students' academic achievement goals.

Aims: The present study tested the hypothesis that students pursuing mastery goals favour instructors who stimulate and challenge them intellectually, whereas those pursuing performance goals favour instructors who present material clearly and provide clear cues about how to succeed.

Design, synthesis, and structure-activity relationship of tropane muscarinic acetylcholine receptor antagonists.

Novel tropane derivatives were characterized as muscarinic acetylcholine receptor antagonists (mAChRs). Through optimization of the structure-activity relationship around the tropane scaffold, the quaternary ammonium salt 34 was identified as a very potent M(3) mAChR antagonist. The compound was functionally active and displayed greater than 24 h duration of action in a mouse model of bronchoconstriction.

Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD.

Design and syntheses of a novel series of muscarinic antagonists are reported. These efforts have culminated in the discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.

Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists.

A novel 4-hydroxyl(diphenyl)methyl substituted quinuclidine series was discovered as a very promising class of muscarinic antagonists. The structure-activity relationships of the connectivity of the diphenyl moiety to the quinuclidine core and around the ring nitrogen side chain are described. Computational docking studies using an homology model of the M(3) receptor readily explained the observed structure-activity relationship of the various compounds.

M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines.

Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M(3) muscarinic acetylcholine receptor antagonists such as 14 (pA(2)=11.0) possessing good sub-type selectivity for M(3) over M(2). The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.

Muscarinic acetylcholine receptor antagonists: SAR and optimization of tyrosine ureas.

SAR exploration of multiple regions of a tyrosine urea template led to the identification of very potent muscarinic acetylcholine receptor antagonists such as 10b with good subtype selectivity for M(3) over M(1). The structure-activity relationships (SAR) and optimization of the tyrosine urea series are described.

Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists.

A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.

Discovery of novel and long acting muscarinic acetylcholine receptor antagonists.

High throughput screening and subsequent optimization led to the discovery of novel quaternary ammonium salts as highly potent muscarinic acetylcholine receptor antagonists with excellent selectivity. Compounds 8a, 13a, and 13b showed excellent inhibitory activity and long duration of action in bronchoconstriction in vivo models in two species via intranasal or intratracheal administration. The novel inhaled muscarinic receptor antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease and other bronchoconstriction disorders.

Discovery of novel 8-azoniabicyclo[3.2.1]octane carbamates as muscarinic acetylcholine receptor antagonists.

In the course of our research program to develop novel muscarinic receptor antagonists for the treatment of COPD, new tropane carbamate derivatives were identified as potent anti-muscarinic agents. The synthesis, structure-activity relationships and pharmacological evaluation that led to the identification of compound 5o, are described.