Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer.

Background: Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether IBD susceptibility variants are also associated with skin cancer susceptibility and if such risk is augmented by use of immune-suppressive therapy.

Methods: The discovery cohort included participants in the UK Biobank.

Single cell RNA sequencing of AML initiating cells reveals RNA-based evolution during disease progression.

The prognosis of most patients with AML is poor due to frequent disease relapse. The cause of relapse is thought to be from the persistence of leukemia initiating cells (LIC's) following treatment. Here we assessed RNA based changes in LICs from matched patient diagnosis and relapse samples using single-cell RNA sequencing.

Thioredoxin reductase is a major regulator of metabolism in leukemia cells.

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models.

Integrated Behavioral Health Role in Helping Pediatricians Find Long Term Mental Health Interventions with the Use of Assessments.

This article explores the role of assessments in integrated behavioral health within a pediatric primary care setting, specifically exploring what valid and reliable standardized assessments may be used and for what concerns the assessment be of most use. The article also considers how assessments used by integrated behavioral health may inform the type of evidenced-based intervention that would be most appropriate and efficacious for the patient, as well as assist in determining if longer term or more formal mental health treatment may be required.

A Noncoding Variant Near PPP1R3B Promotes Liver Glycogen Storage and MetS, but Protects Against Myocardial Infarction.

Context: Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation.

Objective: Investigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease.

Proteins inform survival-based differences in patients with glioblastoma.

Background: Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery.

Methods: For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography-mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months).

Gliomas display distinct sex-based differential methylation patterns based on molecular subtype.

Background: Gliomas are the most common type of primary brain tumor and one of many cancers where males are diagnosed with greater frequency than females. However, little is known about the sex-based molecular differences in glioblastomas (GBMs) or lower grade glioma (non-GBM) subtypes. DNA methylation is an epigenetic mechanism involved in regulating gene transcription.

Sexually dimorphic impact of the iron-regulating gene, , on survival in glioblastoma.

Background: The median survival for patients with glioblastoma (GBM), the most common primary malignant brain tumor in adults, has remained approximately 1 year for more than 2 decades. Recent advances in the field have identified GBM as a sexually dimorphic disease. It is less prevalent in females and they have better survival compared to males.

Phase I Trial of Lithium and Tretinoin for Treatment of Relapsed and Refractory Non-promyelocytic Acute Myeloid Leukemia.

Glycogen synthase kinase-3 (GSK3) inhibitors induce differentiation and growth inhibition of acute myeloid leukemia (AML) cells. Our pre-clinical studies showed GSK3 inhibition leads to sensitization of AML cells to tretinoin-mediated differentiation. We conducted a phase I trial of lithium, a GSK3 inhibitor, plus tretinoin for relapsed, refractory non-promyelocytic AML.

Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma.

Background: Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival.

Financial Analysis of Pediatric Resident Physician Primary Care Longitudinal Outpatient Experience.

Objective: To determine whether residency training represents a net positive or negative cost to academic medical centers, we analyzed the cost of a residency program and clinical productivity of residents and faculty in an outpatient primary care practice with or without residents.

Methods: Patient volume and revenue data (Current Procedural Terminology codes) from an academic primary care general pediatric clinic were evaluated for faculty clinics (faculty only) and resident teaching clinics (longitudinal outpatient experience [LOE]) with 1 to 4 residents per faculty. A detailed cost per resident was determined using a departmental financial model that included salary, benefits, faculty and administrative staff effort, nonpersonnel costs, and institutional graduate medical education support.

Brain tumor biobanking in the precision medicine era: building a high-quality resource for translational research in neuro-oncology.

The growth of precision medicine has made access to biobanks with high-quality, well-annotated neuro-oncology biospecimens critical. Developing and maintaining neuro-oncology biobanks is best accomplished through multidisciplinary collaboration between clinicians and researchers. Balancing the needs and leveraging the skills of all stakeholders in this multidisciplinary effort is of utmost importance.

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence.

Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype.

Models of epigenetic age capture patterns of DNA methylation in glioma associated with molecular subtype, survival, and recurrence.

Background: Models of epigenetic aging (epigenetic clocks) have been implicated as potentially useful markers for cancer risk and prognosis. Using 2 previously published methods for modeling epigenetic age, Horvath's clock and epiTOC, we investigated epigenetic aging patterns related to World Health Organization grade and molecular subtype as well as associations of epigenetic aging with glioma survival and recurrence.

Methods: Epigenetic ages were calculated using Horvath's clock and epiTOC on 516 lower-grade glioma and 141 glioblastoma cases along with 136 nontumor (normal) brain samples.

Epidemiology of Intracranial Gliomas.

Gliomas are the most common primary intracranial neoplasms, which cause significant mortality and morbidity that is disproportionate to their relatively rare incidence. Many potential risk factors for glioma have been studied to date, but only few provide explanation for the number of brain tumor cases identified. The most significant findings include increased risk due to exposure to ionizing radiation and decreased risk with the history of allergy or atopic diseases.

A Novel Glycogen Synthase Kinase-3 Inhibitor Optimized for Acute Myeloid Leukemia Differentiation Activity.

Standard therapies used for the treatment of acute myeloid leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, acute promyelocytic leukemia, can be cured by differentiation therapy using regimens containing all-trans retinoic acid.

Computational identification of multi-omic correlates of anticancer therapeutic response.

Background: A challenge in precision medicine is the transformation of genomic data into knowledge that can be used to stratify patients into treatment groups based on predicted clinical response. Although clinical trials remain the only way to truly measure drug toxicities and effectiveness, as a scientific community we lack the resources to clinically assess all drugs presently under development. Therefore, an effective preclinical model system that enables prediction of anticancer drug response could significantly speed the broader adoption of personalized medicine.

Epidemiology of gliomas.

Gliomas are the most common type of primary intracranial tumors. Some glioma subtypes cause significant mortality and morbidity that are disproportionate to their relatively rare incidence. A very small proportion of glioma cases can be attributed to inherited genetic disorders.

Pharmacogenomic approach to identify drug sensitivity in small-cell lung cancer.

There are currently no molecular targeted approaches to treat small-cell lung cancer (SCLC) similar to those used successfully against non-small-cell lung cancer. This failure is attributable to our inability to identify clinically-relevant subtypes of this disease. Thus, a more systematic approach to drug discovery for SCLC is needed.

Memory priming and trial spacing effects in Pavlovian learning.

Conditioning trials that are massed in time produce less conditioning than those that are spaced in time. Four experiments with rat subjects examined whether a recent conditioning trial interferes with conditioning on the next trial by temporarily "priming" information in short-term memory (e.g.

Inhibition of Salmonella typhimurium on agar medium and poultry skin by ultraviolet energy.

Ultraviolet radiation (UV) was effective in destroying Salmonella typhimurium on agar plates and poultry skin. Agar plates inoculated with varying numbers of colony-forming units (CFU) of S. typhimurium (1.

The use of ultraviolet radiation to reduce Salmonella and psychrotrophic bacterial contamination on poultry carcasses.

Broiler carcasses were subjected to ultraviolet (UV) energy (doses range from 82,560 to 86,400 muWs/cm2) at wavelength of 253.7 nm to evaluate the potential of this treatment for improving the microbiological quality of broiler carcasses. Broiler chicken halves were inoculated with a marker strain of Salmonella typhimurium 5 min prior to treatment.

Effects of 42- and 2450-MHz dielectric heating on nutrition-related properties of soybeans.

Dielectric heating at frequencies of 42 and 2450 MHz was applied to whole soybeans of natural moisture content for varies exposure times. The minimum energy absorbed (MEA) was calculated from moisture-loss and temperature-elevation data. Biochemical analyses were performed to determine protein dispersibility index (PDI), nitrogen solubility index (NSI), and trypsin-inhibitor, urease, lipoxygenase, and peroxidase activities.