Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer.

Background And Objective: Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC.

Prosthetic Nasal Reconstruction.

Prosthetic nasal reconstruction provides a restorative option for patients with nasal defects, and these can be retained with a variety of methods including adhesives and implants. These prostheses can significantly improve appearance, self-esteem, and quality of life for patients and they restore many functions of the external nose. Traditional fabrication methods are often used by the skilled professionals who make these custom prostheses, but digital technology is improving the workflow for design and fabrication of silicone nasal prostheses.

Pharmacy Students' Perspectives on Human Resource Management: An Examination of Knowledge and Attitudes.

(1) Background: This study aims to examine pharmacy students' perceptions of their knowledge and competencies in human resource management (HRM) while also investigating their attitudes toward the educational content provided in a didactic HRM course. (2) Methods: A survey evaluating both course knowledge (pre and post) and attitudes was administered to students enrolled in an HRM class. Data were analyzed using descriptive statistics and measures of associations.

Longitudinal Monitoring of Circulating Tumor DNA to Assess the Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Genitourinary Malignancies.

Purpose: Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker demonstrating improved assessment of treatment response in patients receiving immune checkpoint inhibitors (ICIs). Here, we performed a pilot study to support the role of ctDNA for longitudinal treatment response monitoring in patients with advanced genitourinary (GU) malignancies receiving ICIs.

Materials And Methods: Patients with histologically confirmed advanced GU malignancies were prospectively enrolled.

Elucidation of the GSK3α Structure Informs the Design of Novel, Paralog-Selective Inhibitors.

Glycogen synthase kinase 3 (GSK3) remains a therapeutic target of interest for diverse clinical indications. However, one hurdle in the development of small molecule GSK3 inhibitors has been safety concerns related to pan-inhibition of both GSK3 paralogs, leading to activation of the Wnt/β-catenin pathway and potential for aberrant cell proliferation. Development of GSK3α or GSK3β paralog-selective inhibitors that could offer an improved safety profile has been reported but further advancement has been hampered by the lack of structural information for GSK3α.

Adsorption and Electropolymerization of -Aminophenol Reduces Reproducibility of Electrochemical Immunoassays.

This paper investigates the electrochemical behavior of -aminophenol (PAP) on commercially available carbon screen-printed electrodes (CSPEs) and gold screen-printed electrodes (GSPEs) at neutral and basic pHs for the development of inexpensive immunoassays. The electrochemical oxidative signal from PAP results from its adsorption to the electrode. The formation of self-assembled monolayers on gold electrodes prevented PAP adsorption but also reduced its oxidative current, confirming that adsorption increases signal production.

Clinical Impact and Generalizability of a Computer-Assisted Diagnostic Tool to Risk-Stratify Lung Nodules With CT.

Objective: To evaluate whether an imaging classifier for radiology practice can improve lung nodule classification and follow-up.

Methods: A machine learning classifier was developed and trained using imaging data from the National Lung Screening Trial (NSLT) to produce a malignancy risk score (malignancy Similarity Index [mSI]) for individual lung nodules. In addition to NLST cohorts, external cohorts were developed from a tertiary referral lung cancer screening program data set and an external nonscreening data set of all nodules detected on CT.

Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin.

Elevated levels of circulating cell-free hemoglobin (CFH) are an integral feature of several clinical conditions including sickle cell anemia, sepsis, hemodialysis and cardiopulmonary bypass. Oxidized (Fe, ferric) hemoglobin contributes to the pathophysiology of these disease states and is therefore widely studied in experimental models, many of which use commercially sourced CFH. In this study, we treated human endothelial cells with commercially sourced ferric hemoglobin and observed the appearance of dense cytoplasmic aggregates (CAgg) over time.

Trace Oxygen Affects Osmium Redox Polymer Synthesis for Wired Enzymatic Biosensors.

Electrochemical sensors that utilize enzymes are a sensitive, inexpensive means of detecting biologically relevant analytes. These sensors are categorized based on their construction and method of signal transport. Type I sensors consist of a crosslinked enzyme on an electrode surface and are potentially subject to interference from byproducts and other biological analytes.

Longitudinal EEG model detects antisense oligonucleotide treatment effect and increased UBE3A in Angelman syndrome.

Angelman syndrome is a neurodevelopmental disorder caused by deficiency of the maternally inherited gene in neurons. Antisense oligonucleotide therapies are under development to reinstate UBE3A protein production. Non-invasive biomarkers to detect target engagement and treatment response are needed to support clinical trials.

Caring callers: the impact of the telephone reassurance program on homebound older adults during COVID-19.

During the COVID-19 pandemic, older adults experienced great levels of social isolation and feelings of loneliness. We developed a telephone reassurance program, Caring Callers, to provide a weekly phone call to socially isolated older adults. Dyads were created which comprised of a Senior Companion volunteer and a homebound older adult.

Altered Blood Flow in the Ophthalmic and Internal Carotid Arteries in Patients with Age-Related Macular Degeneration Measured Using Noncontrast MR Angiography at 7T.

Background And Purpose: Age-related macular degeneration is associated with reduced perfusion of the eye; however, the role of altered blood flow in the upstream ophthalmic or internal carotid arteries is unclear. We used ultra-high-field MR imaging to investigate whether the diameter of and blood flow in the ophthalmic artery and/or the ICA are altered in age-related macular degeneration and whether any blood flow changes are associated with disease progression.

Materials And Methods: Twenty-four patients with age-related macular degeneration and 13 similarly-aged healthy controls participated.

Discovery of Potent and Brain-Penetrant Tau Tubulin Kinase 1 (TTBK1) Inhibitors that Lower Tau Phosphorylation In Vivo.

Structural analysis of the known NIK inhibitor bound to the kinase domain of TTBK1 led to the design and synthesis of a novel class of azaindazole TTBK1 inhibitors exemplified by (cell IC: 571 nM). Systematic optimization of this series of analogs led to the discovery of , a potent (cell IC: 315 nM) and selective TTBK inhibitor with suitable CNS penetration (rat K: 0.32) for in vivo proof of pharmacology studies.

Radiomics in the evaluation of lung nodules: Intrapatient concordance between full-dose and ultra-low-dose chest computed tomography.

Purpose: The purpose of this study was to retrospectively evaluate the quantitative and qualitative intrapatient concordance of pulmonary nodule risk assessment by commercially available radiomics software between full-dose (FD) chest-CT and ultra-low-dose (ULD) chest CT.

Materials And Methods: Between July 2013 and September 2015, 68 patients (52 men and16 women; mean age, 65.5±10.

Temporal Progression of Excitotoxic Calcium Following Distal Middle Cerebral Artery Occlusion in Freely Moving Mice.

Ischemic stroke is recognized as one of the leading causes of adult disability, morbidity, and death worldwide. Following stroke, acute neuronal excitotoxicity can lead to many deleterious consequences, one of which is the dysregulation of intracellular calcium ultimately culminating in cell death. However, to develop neuroprotective treatments that target neuronal excitotoxicity, it is essential to know the therapeutic time window for intervention following an ischemic event.

Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells.

Background: Appropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect.

Acute inhibition of the CNS-specific kinase TTBK1 significantly lowers tau phosphorylation at several disease relevant sites.

Hyperphosphorylated tau protein is a pathological hallmark of numerous neurodegenerative diseases and the level of tau pathology is correlated with the degree of cognitive impairment. Tau hyper-phosphorylation is thought to be an early initiating event in the cascade leading to tau toxicity and neuronal death. Inhibition of tau phosphorylation therefore represents an attractive therapeutic strategy.

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility.

Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy).

Utilizing the Senior Companion Program as a platform for a culturally informed caregiver intervention: Results from a mixed methods pilot study.

To address the need for accessible, affordable, and sustainable Alzheimer's disease and related dementia caregiver interventions with minority populations, we developed the Senior Companion Program Plus, a three-phase pilot study that used a mixed methods experimental design. The intent was to determine if participation in a lay provider, peer-led psychoeducational intervention designed for African American Alzheimer's disease and related dementia caregivers ( = 16) improved caregiver burden and/or stress, coping skills, and social support. Focus groups with Senior Companions informed the intervention design.

Beyond Linear Elastic Modulus: Viscoelastic Models for Brain and Brain Mimetic Hydrogels.

With their high degree of specificity and investigator control, in vitro disease models provide a natural complement to in vivo models. Especially in organs such as the brain, where anatomical limitations make in vivo experiments challenging, in vitro models have been increasingly used to mimic disease pathology. However, brain mimetic models may not fully replicate the mechanical environment in vivo, which has been shown to influence a variety of cell behaviors.

Dorsiflexion Range of Motion in Copers and Those with Chronic Ankle Instability.

The Cumberland Ankle Instability Tool (CAIT) is used to classify individuals as ankle sprain copers, or as one suffering from chronic ankle instability (CAI). However, literature examining factors contributing to these classifications on the CAIT is lacking, as the CAIT itself does not offer explanations for specific anthropometric measures that influence a patient's classification. Therefore, the purpose was to determine if there was a difference between dorsiflexion active range of motion (AROM) between copers, those with CAI, and a healthy control group.

Effect of Electrospun Fiber Mat Thickness and Support Method on Cell Morphology.

Electrospun fiber mats (EFMs) are highly versatile biomaterials used in a myriad of biomedical applications. Whereas some facets of EFMs are well studied and can be highly tuned (e.g.