Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication.

Background: Neddylation (NAE) inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report the cytotoxic vulnerability to NAE inhibitors in a subset of glioblastoma (GBM) preclinical models and identify genetic alterations and biological processes underlying differential response.

Methods: GBM DNA sequencing and transcriptomic data were queried for genes associated with response to NAE inhibition; candidates were validated by molecular techniques.

Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for Patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT.

Purpose: Patients with glioblastoma (GBM) have a dismal prognosis. Although the DNA alkylating agent temozolomide (TMZ) is the mainstay of chemotherapy, therapeutic resistance rapidly develops in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models.

Synthesis, microstructural and optical characterizations of sol-gel grown gadolinium doped cerium oxide ceramics.

In this study, through the utilization of the sol-gel combustion tactic, gadolinium (Gd)-doped cerium oxide (CeO), CeGdO ( = 0.00, 0.10, 0.

Large Cell Neuroendocrine Carcinoma of the Gallbladder: Where Survival Is a Rare Entity - Case Report and Review of the Literature.

Introduction: Carcinoma of the gallbladder is extremely rare, papillary adenocarcinoma comprises 90% of these cases. Although neuroendocrine neoplasms (NENs) comprise 0.5% of the cases of gallbladder cancer, the incidence is rising.

Performance of HDP-Gestosis Score and Ophthalmic Artery Doppler in Prediction of Pre-eclampsia.

Purpose Of Study: To study the predictive accuracy of maternal characteristics, mean arterial pressure, uterine artery doppler and maternal ophthalmic artery doppler in second trimester for subsequent development of pre-eclampsia.

Methods: A prospective cohort study of 440 women at 19-24 weeks' gestation. It included recording of maternal demographic characteristics and calculation of HDP Gestosis Score, measurement of MAP and ultrasound evaluation for fetal anatomy, Uterine artery doppler and maternal ophthalmic artery doppler.

Sodium Alginate-CuS Nanostructures Synthesized at the Gel-Liquid Interface: An Efficient Photocatalyst for Redox Reaction and Water Remediation.

The use of visible light to propel chemical reactions is an exciting area of study that is crucial in the current socioeconomic environment. However, various photocatalysts have been developed to harness visible light, which consume high energy during synthesis. Thus, synthesizing photocatalysts at gel-liquid interfaces in ambient conditions is of scientific importance.

Takotsubo Cardiomyopathy Associated With Acute Pancreatitis.

Takotsubo cardiomyopathy is classically associated with emotional stress in middle-aged women. In clinical practice, physical stressors are a more common cause of Takotsubo cardiomyopathy. Here, we present two patients who had acute pancreatitis as a physical stressor that caused Takotsubo cardiomyopathy, and an additional 13 cases identified in the literature.

Granular Cell Tumor of the Ascending Colon.

Granular cell tumor (GCT) was first described by Abrikossoff in 1926. It is a mostly benign tumor with rare malignant transformation. It is defined as a soft tissue neoplasm with abundant eosinophilic cytoplasm.

Preclinical target validation for non-addictive therapeutics development for pain.

Introduction: The Helping to End Addiction Long-term Initiative supports a wide range of programs to develop new or improved prevention and opioid addiction treatment strategies. An essential component of this effort is to accelerate development of non-opioid pain therapeutics. In all fields of medicine, therapeutics development is an arduous process and late-stage translational efforts such as clinical trials to validate targets are particularly complex and costly.

Trends in Palliative Care, Hospice Utilization, and Outcomes in Hospitalized Pancreatic Cancer Patients: A Nationwide Analysis.

Background and objective The prognosis of pancreatic cancer (PC) is generally poor. PC responds only modestly to chemotherapy and chemoradiation, and surgical resection remains the only curative option. The risk of recurrence is high.

Morphology-Tuned Electrochemical Immunosensing of a Breast Cancer Biomarker Using Hierarchical Palladium Nanostructured Interfaces.

Metallic nanostructures are considered attractive candidates for designing novel biosensors due to their enormously significant surface area, accelerated kinetics, and improved affinity. Controllable morphological tuning of metallic nanostructures on sensing interfaces is crucial for attaining clinically relevant sensitivity and exquisite selectivity in a complex biological environment. Therefore, a facile, convenient, and robust one-step electroreduction method was employed to develop different morphological variants of palladium (Pd) nanostructures supported onto oxidized carbon nanotubes to facilitate label-free electrochemical immunosensing of HER2.

A platinum nanoparticle doped self-assembled peptide bolaamphiphile hydrogel as an efficient electrocatalyst for the hydrogen evolution reaction.

Noble metal-based nanomaterials have shown great potential for catalytic application with higher selectivity and activity. Owing to their self-assembly properties with various molecular interactions, peptides play an essential role in the controlled synthesis of noble metal-based catalysts with high surface area. In this work, a phenylalanine (F) and tyrosine (Y) based peptide bolaamphiphile is prepared by solution-phase peptide synthesis.

Early Colonoscopy in Hospitalized Patients With Acute Lower Gastrointestinal Bleeding: A Nationwide Analysis.

Background: Performing colonoscopy within 24 h of presentation to the hospital is the accepted standard of care for patients with an acute lower gastrointestinal bleed (LGIB). Previous studies have failed to demonstrate the benefit of early colonoscopy (EC) on mortality. In this study, we wanted to see if there was a change in inpatient deaths (primary outcome), length of stay (LOS), and hospitalization charges (TOTCHG) (secondary outcomes) with EC compared to previous studies.

Ingested Potassium Chloride Pills on Imaging Misdiagnosed As Foreign Bodies in the Stomach: An Insight on Radiopaque/Hyperdense Substances in the Gastrointestinal Tract.

Foreign bodies are very common in the GI tract. Around 100,000 cases are reported each year in the United States. A total of 80% of those foreign body ingestions occur in the pediatric population.

Artificial intelligence optimized image segmentation techniques for renal cyst detection.

The vast number of image modalities available nowadays has given rise and access to a number of medical images. These images perhaps suffer issues such as low contrast, noise, ill-defined boundaries and poor visualisation. Therefore, a need for effective segmentation arises.

An Extremely Rare Case of Rectal Signet Ring Cell Carcinoma.

Signet ring cell carcinoma of the rectum is a rare variant of colorectal cancer. When found, it is often diagnosed in late stages and has poor prognosis. This case depicts a patient with a history of Crohn's disease who presented to the hospital for perirectal abscesses.

Improving Surgical Triage in Spine Clinic: Predicting Likelihood of Surgery Using Machine Learning.

Background: Correctly triaging patients to a surgeon or a nonoperative provider is an important part of the referral process. Clinics typically triage new patients based on simple intake questions. This is time-consuming and does not incorporate objective data.

A focus on the neural exposome.

Many neurological disorders have complex etiologies that include noninheritable factors, collectively called the neural exposome. The National Institute of Neurological Disorders and Stroke is developing a new office with goals to advance our understanding of the multiple causes of neurological illness and to enable the development of more effective interventions.

PTEN loss drives resistance to the neddylation inhibitor MLN4924 in glioblastoma and can be overcome with TOP2A inhibitors.

Background: Neddylation inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report vulnerability to MLN4924 or pevonedistat (a neddylation inhibitor) in a subset of glioblastoma (GBM) preclinical models and identify biomarkers, mechanisms, and signatures of differential response.

Methods: GBM sequencing data were queried for genes associated with MLN4924 response status; candidates were validated by molecular techniques.

Stroke: What's Sleep Got to Do With It?

Ischemic strokes most often occur between 6 am and 12 am after awakening from sleep but up to 30% occur during sleep. Wake-up strokes (WUS) are new focal neurological deficit(s) persisting for ≥ 24 hours attributable to an ischemic event present on patient awakening. Obstructive sleep apnea (OSA) is a major risk factor for WUS because it compounds the instability of the morning environment and increases the likelihood of cardiovascular events, including hypertension, atrial fibrillation, right-to-left shunts, and stroke.

Idiopathic Sclerosing Mesenteritis: An Extremely Rare Cause of Mesenteric Mass.

Idiopathic sclerosing mesenteritis (ISM) is an extremely rare condition in which mesenteric adipose tissue undergoes necrotic and fibrotic changes. It is also known as "retractile mesenteritis", "mesenteric panniculitis" or "fat necrosis of the mesentery". Most cases are seen in Caucasian males between the fifth and seventh decades of life.

Recurrent aseptic liver abscesses in a patient with Crohn's disease: True infection or a Crohn's flare?

A liver abscess is identified as a rare extraintestinal manifestation of Crohn's disease, with an incidence of approximately 150 in 100,000 patients with this condition. In many of these patients, infectious causes are identified, and the patient's condition is often noted to improve with antibiotics. An aseptic abscess (AA) is an increasingly recognized entity, especially in patients with inflammatory bowel disease, where repetitive evaluations to identify the infectious cause are futile.

Neuromuscular and Vascular Hamartoma: Starting Point in Crohn's Disease?

Neuromuscular and vascular hamartoma (NMVH) is a benign and rare lesion comprising abnormal proliferation of cellular elements in the mucosa of the small intestine. NMVH shares certain histological features with inflammatory conditions like Crohn's disease, radiation and ischemic enteritis, and has been a part of ongoing debate since it was first described in 1982. We intend to describe an interesting case of small bowel obstruction caused by NMVH and emphasize the importance of keeping it as an important differential diagnosis in cases of small bowel obstructions for general practitioners and gastroenterologists.

Efficacy of a Smart Insulin Pen Cap for the Management of Patients with Uncontrolled Type 2 Diabetes: A Randomized Cross-Over Trial.

Background: We studied a smart insulin pen cap that can be plugged to several brand of insulin pens, to track insulin administration via smart-phone Bluetooth technology, with alarm/reminder system aiming.

Methods: This pilot randomized, cross-over design study assessed the use of a smart insulin pen cap in improving adherence, glycemic control and patient satisfaction in insulin-treated patients with poorly controlled type 2 diabetes. Eighty patients on basal insulin ± oral agents with hemoglobin A1C (HbA1c) between 7.

Gastropancreatic Fistula: A Rare Complication of Peptic Ulcer Disease.

Peptic ulcer disease (PUD) has a significant health burden. Penetration is a rare complication of PUD, where an ulcer erodes into another organ. To the best of our knowledge, we present the fourth case in the literature where a gastric ulcer has penetrated the pancreas.