WD repeat domain 5 (WDR5) inhibitors: a patent review (2016-present).

Introduction: WDR5 is an epigenetic scaffolding protein that has attracted significant interest as an anti-cancer drug target, especially in MLL-rearranged leukemias. The most druggable 'WIN-site' on WDR5, which tethers WDR5 to chromatin, has been successfully targeted with multiple classes of exquisitely potent small-molecule protein-protein interaction inhibitors. Earlier progress has also been made on the development of WDR5 degraders and inhibitors at the 'WBM-site' on the opposite face of WDR5.

A team-based approach to type 2 diabetes and cardiovascular care.

The Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) program is an innovative, patient-centered system of care developed by the University Hospitals Harrington Heart and Vascular Institute in Cleveland, Ohio in the US for the management of high-risk patients with type 2 diabetes (T2D) and prediabetes at high risk for cardiovascular-kidney-metabolic (CKM) syndrome and its consequences. At its core, CINEMA is a multidisciplinary team of care experts, working together outside of traditional silos. The patient meets with the entire team up to 4 times each year to address all aspects of cardiovascular (CV) and T2D care.

An Access-Focused Patient-Centric Value Assessment Framework for Medication Formulary Decision-Making in Immune-Mediated Inflammatory Diseases.

The healthcare system in the United States (US) is complex and often fragmented across national and regional health plans which exhibit substantial variability in benefit design and formulary policies for accessing medications. We propose an access-focused value assessment framework for formulary decision-making for medications to manage immune-mediated inflammatory diseases (IMIDs), where patients are at the center of this framework. Formulary decision-making for IMID medications can be a challenging, even daunting, task with continuously evolving and enhanced treat-to-target goals.

Fis1 regulates mitochondrial morphology, bioenergetics, and removal of mtDNA damage in irradiated glioblastoma cells.

In response to external stress, mitochondrial dynamics is often disrupted, but the associated physiologic changes are often uncharacterized. In many cancers, including glioblastoma (GBM), mitochondrial dysfunction has been observed. Understanding how mitochondrial dynamics and physiology contribute to treatment resistance will lead to more targeted and effective therapeutics.

Outcomes after per oral pyloromyotomy based on gastroparesis etiology.

Background: Per oral pyloromyotomy (POP) has been shown to be effective in patients with gastroparesis. The three most common etiologies of gastroparesis are diabetic, postsurgical, and idiopathic. Our aim was to compare outcomes after POP based on the etiology of gastroparesis.

Consensus Radiation Treatment Planning Guidelines Using (68)Ga-DOTATATE PET/CT For Resected Meningiomas.

Purpose: Meningiomas are the most common primary intracranial tumor. Somatostatin receptor 2 is almost universally expressed in meningioma tissue. For patients who require adjuvant radiation, somatostatin receptor based (68)Ga-DOTATATE positron emission tomography (PET) imaging can detect additional or residual disease not discernible on magnetic resonance imaging.

HIGH BODY MASS INDEX IS ASSOCIATED WITH LOWER ADALIMUMAB SERUM LEVELS AND HIGHER DISEASE ACTIVITY IN NON-INFECTIOUS UVEITIS.

Purpose: Adalimumab, a TNF-alpha inhibitor, is the only FDA-approved biologic for non-infectious uveitis (NIU). However, treatment responses vary, potentially due to interindividual pharmacokinetic differences influenced by body mass index (BMI). This study aimed to evaluate the impact of BMI on adalimumab serum trough levels and therapeutic efficacy in patients with NIU.

Evaluation of a far ultraviolet-C device for decontamination of portable equipment in clinical areas.

Contaminated portable equipment may contribute to transmission of health care-associated pathogens. We demonstrated that a wall-mounted far ultraviolet-C light technology that delivers far ultraviolet-C only when people are not present was effective in reducing contamination on in-use patient transport chairs and physical therapy equipment in equipment rooms. The technology could potentially be used as an adjunctive measure for decontamination of portable equipment in clinical areas.

Diagnostic accuracy of neonatal structural MRI scores to predict 6-year motor outcomes of children born very preterm.

Aims: This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA.

Methods: Infants born < 31-weeks gestational age (GA) returning for 6-year follow-up were included. Early and Term sMRI were scored using a validated method, deriving white matter, cortical grey matter, deep grey matter, cerebellar and global brain abnormality scores (GBAS).

Metastatic Adenoid Cystic Carcinoma to the Pancreas: A Case Report and Review of the Literature.

Although more than 90% of pancreatic tumors represent primary tumors, specifically ductal adenocarcinomas, metastatic tumors are not infrequent at this site. Metastasis of salivary gland tumors to the pancreas is exceedingly rare, with only a few cases reported in the English-language medical literature. Here, we report a patient with metastatic adenoid cystic carcinoma to the pancreas, 24 months following the initial diagnosis, and review the available literature on secondary tumors located in the pancreas with an emphasis on tumors of salivary gland origin.

Psychometric evaluation of the Autism Symptom Dimensions Questionnaire.

Aim: To replicate and extend previous psychometric findings for the Autism Symptom Dimensions Questionnaire (ASDQ).

Method: Using a cross-sectional design in two samples, including a total of 3366 children and adolescents (aged 2-17 years; 1399 with autism spectrum disorder) and a small case series, factor structure, measurement invariance, reliability, construct validity, screening and diagnostic efficiency, and detection of reliable change were examined for the ASDQ.

Results: Strong psychometric properties were observed, including replicable factor structure, strong measurement invariance, adequate-to-excellent scale and conditional reliability, strong convergent and discriminant validity, and good screening efficiency.

Who feels safe calling 911: are prior experiences of anti-Black racial discrimination associated with hesitancy seeking emergency medical services in the event of accidental drug overdose? - a study protocol.

Background: Racial discrimination is associated with health disparities among Black Americans, a group that has experienced an increase in rates of fatal drug overdose. Prior research has found that racial discrimination in the medical setting may be a barrier to addiction treatment. Nevertheless, it is unknown how experiences of racial discrimination might impact engagement with emergency medical services for accidental drug overdose.

Comparing new tools of artificial intelligence to the authentic intelligence of our global health students.

Introduction: The transformative feature of Artificial Intelligence (AI) is the massive capacity for interpreting and transforming unstructured data into a coherent and meaningful context. In general, the potential that AI will alter traditional approaches to student research and its evaluation appears to be significant. With regard to research in global health, it is important for students and research experts to assess strengths and limitations of GenAI within this space.

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).

Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts).

A multicontinental dataset of butterfly thermal physiological traits.

Butterflies serve as key indicators of climate change impacts such as shifts in emergence timing and shifts in geographic range and distribution. However, the development of commonly used ecological forecasts based on butterfly physiological tolerance of temperature change has lagged behind that of other taxonomic groups. Here, we provide a series of related datasets comprising butterfly thermal physiological traits to enable such forecasts.

Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.

The cyclin D1-Cyclin-Dependent Kinases 4 and 6 (CDK4/6) complex is crucial for the development of melanoma. We previously demonstrated that targeting CDK4/6 using small molecule inhibitors (CDK4/6i) suppresses Braf melanoma growth in vitro and in vivo through induction of cellular senescence. However, clinical trials investigating CDK4/6i in melanoma have not yielded successful outcomes, underscoring the necessity to enhance the therapeutic efficacy of CDK4/6i.

Gene Signatures and Oncology Treatment Implications.

Gene expression signatures (GES) are a powerful tool in oncology used for classification, prognostication, and therapeutic response prediction of malignancies. In this article, we review the disease site guidelines by the National Comprehensive Cancer Network that use GES for treatment planning and clinical use. We identified 4 cancer types for which treatment decisions are frequently influenced by GES.

Use of Intraoperative Hemostatic Checklists for Blood Management in Patients Undergoing Cardiac Surgery: A Scoping Review.

Background: Using intraoperative hemostatic checklists may improve rates of surgical re-exploration and utilization of allogenic blood products in patients undergoing cardiac surgery. In this review, the authors explore the current evidence describing the impact of using intraoperative hemostatic checklists on reducing rates of surgical bleeding and perioperative blood product transfusion in this group of patients.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic information was obtained via sources that included Scopus, MEDLINE, EMBASE, and the Cochrane Library.

Predictors and Long-Term Prognostic Significance of Bailout Stenting During Percutaneous Coronary Interventions With Sirolimus-Coated Balloon: A Subanalysis of the Eastbourne Study.

Percutaneous coronary intervention (PCI) with drug-coated balloon (DCB) has been expanding progressively in recent years. Convincing evidence demonstrated the ability of some DCB to promote positive vessel remodeling, with potential clinical benefits at follow-up. When PCI with DCB results in suboptimal angiographic results (residual stenosis >30% or type C to F dissection), bailout stenting (BS) implantation is recommended to mitigate the risk of abrupt vessel occlusion or restenosis.

BEST1 VARIANT ASSOCIATED WITH AN ATYPICAL MACULAR AND PERIPHERAL RETINAL PHENOTYPE.

Purpose: Best vitelliform macular dystrophy is an inherited macular dystrophy associated with over 250 pathogenic variants of the Bestrophin-1 ( BEST1 ) gene. Although several types of lesions of best vitelliform macular dystrophy are well-described, reports of phenotypic variations associated with rare genetic variants are limited.

Methods: This was a retrospective case series performed in 2021 at a tertiary eye care center.