Role of scaffold proteins in the heterogeneity of glioblastoma.

Glioblastoma (GB) is a highly heterogeneous type of incurable brain cancer with a low survival rate. Intensive ongoing research has identified several potential targets; however, GB is marred by the activation of multiple pathways, and thus common targets are highly sought. The signal regulatory scaffold IQGAP1 is an oncoprotein implicated in GB.

Early-Stage Moderate Alcohol Feeding Dysregulates Insulin-Related Metabolic Hormone Expression in the Brain: Potential Links to Neurodegeneration Including Alzheimer's Disease.

Background: Alzheimer's disease (AD), one of the most prevalent causes of dementia, is mainly sporadic in occurrence but driven by aging and other cofactors. Studies suggest that excessive alcohol consumption may increase AD risk.

Objective: Our study examined the degree to which short-term moderate ethanol exposure leads to molecular pathological changes of AD-type neurodegeneration.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests.

Ever Expanding Morphologic Patterns of Mesonephric-like Adenocarcinomas of the Uterine Corpus: A Report of Two Tumors and a Brief Review of the Literature.

Mesonephric-like adenocarcinoma (MLA) of the endometrium shows a variety of morphologic appearances, including small glands, tubules with eosinophilic materials in the lumen, prominent papillary patterns, spindled cells, solid formations, and corded and hyalinized patterns. Unique morphology, characteristic immunohistochemical staining patterns, molecular alterations, and awareness of the pathologists make it possible to identify this tumor accurately. This report of two additional morphologic patterns, intestinal goblet cells mimicking intestinal-type mucinous carcinoma and squamous differentiation with spindle and epithelioid cells mimicking carcinosarcoma of the endometrium will expand the literature on MLA.

Agent Orange Herbicidal Toxin-Initiation of Alzheimer-Type Neurodegeneration.

Background: Agent Orange (AO) is a Vietnam War-era herbicide that contains a 1 : 1 ratio of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Emerging evidence suggests that AO exposures cause toxic and degenerative pathologies that may increase the risk for Alzheimer's disease (AD).

Objective: This study investigates the effects of the two main AO constituents on key molecular and biochemical indices of AD-type neurodegeneration.

Long-term Treatment of Pediatric Metastatic Papillary Thyroid Cancer With Lenvatinib.

Papillary thyroid carcinoma (PTC) is the most common pediatric thyroid malignancy and incidence is increasing. Standard treatment for PTC in pediatric patients includes surgical intervention, suppression of TSH with levothyroxine, and radioactive iodine therapy (RAI) in select patients. In the setting of metastatic PTC or PTC refractory to RAI therapy, tyrosine kinase inhibitors (TKIs), such as lenvatinib, may be used.

Complexity, Lethality, and the Perverse Imagination: Modelling Nonstate Actors' Means of Attack.

In the pursuit of security, state actors presume a linear relationship between the lethality and complexity of various means of attack. They deploy resources and research programs to overcome the inherent or "analytic" complexity of increasingly lethal means of their own (think of programs to develop nuclear weapons and other highly lethal munitions), and they impose security, legal and regulatory regimes to increase the imposed or "synthetic" complexity opponents must overcome to appropriate or adopt the means they develop. Nonstate actors such as terrorists overcome the challenges of complexity by imaginatively seeking new ways to operate in an alternative high lethality/low complexity space.

Association of maternal education, neighborhood deprivation, and racial segregation with gestational age at birth by maternal race/ethnicity and United States Census region in the ECHO cohorts.

Background: In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region.

Methods: We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019.

Research Priorities for Expansion of Opioid Use Disorder Treatment in the Community Pharmacy.

In the last decade, the U.S. opioid overdose crisis has magnified, particularly since the introduction of synthetic opioids, including fentanyl.

Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer's Disease (Type 3 Diabetes).

Malignant brain aging corresponds to accelerated age-related declines in brain functions eventually derailing the self-sustaining forces that govern independent vitality. Malignant brain aging establishes the path toward dementing neurodegeneration, including Alzheimer's disease (AD). The full spectrum of AD includes progressive dysfunction of neurons, oligodendrocytes, astrocytes, microglia, and the microvascular systems, and is mechanistically driven by insulin and insulin-like growth factor (IGF) deficiencies and resistances with accompanying deficits in energy balance, increased cellular stress, inflammation, and impaired perfusion, mimicking the core features of diabetes mellitus.

Bilateral Tibial Tubercle Avulsion Fractures With an Associated Patellar Tendon Avulsion in an Adolescent Patient.

Tibial tubercle fractures in pediatric patients are increasing in frequency as more children participate in sports. These injuries are often seen in boys engaging in jumping activities before closure of their proximal tibial physis. Bilateral tibial tubercle fractures have been reported in the literature, but less frequent are associated patellar tendon ruptures with fracture of the tubercle.

Agent Orange Causes Metabolic Dysfunction and Molecular Pathology Reminiscent of Alzheimer's Disease.

Background: Agent Orange, an herbicide used during the Vietnam War, contains 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Agent Orange has teratogenic and carcinogenic effects, and population-based studies suggest Agent Orange exposures lead to higher rates of toxic and degenerative pathologies in the peripheral and central nervous system (CNS).

Objective: This study examines the potential contribution of Agent Orange exposures to neurodegeneration.

Low-level expression of human Epidermal growth Factor Receptor-2 (HER2) in High-Grade Mullerian Tumors: Implications for therapy decision making.

Introduction: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas.

Documented Visio-Vestibular Examination and Anticipatory Guidance for Pediatric Concussion Patients.

Objectives: Pediatric concussion patients are frequently managed in the primary care or acute care settings. Optimal care includes vision and vestibular assessments, as well as targeted anticipatory guidance for return to school and activity. We aimed to examine clinical practices related to the evaluation and management of concussion patients at children's hospital-based emergency department (ED) and primary care/urgent care settings.

Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms.

Background: Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.

Methods: This study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association.

"ARREST ALL STREET MENDICANTS AND BEGGARS:" HOMELESSNESS, SOCIAL COOPERATION, AND THE COMMITMENTS OF DEMOCRATIC POLICING.

In "Are Police the Key to Public Safety?: The Case of the Unhoused," Barry Friedman argues that one of the problems with policing in the United States is that it encompasses too narrow a view of public safety. In the case of homelessness, this narrow view fails to understand that providing shelter and subsistence to the unhoused is providing them with a basic form of safety as well. By this view, enforcing most laws against the behaviors associated with homelessness is unjust because it penalizes people for seeking a form of personal security that the government should have provided them with.