Phase separation promotes a highly active oligomeric scaffold of the MLL1 core complex for regulation of histone H3K4 methylation.

Enzymes that regulate the degree of histone H3 lysine 4 (H3K4) methylation are crucial for proper cellular differentiation and are frequently mutated in cancer. The Mixed lineage leukemia (MLL) family of enzymes deposit H3K4 mono-, di-, or trimethylation at distinct genomic locations, requiring precise spatial and temporal control. Despite evidence that the degree of H3K4 methylation is controlled in part by a hierarchical assembly pathway with key subcomplex components, we previously found that the assembled state of the MLL1 core complex is not favored at physiological temperature.

Assessing the accuracy of electronic health record gender identity and REaL data at an academic medical center.

Background: Collection of accurate patient race, ethnicity, preferred language (REaL) and gender identity in the electronic health record (EHR) is essential for equitable and inclusive care. Misidentification of these factors limits quality measurement of health outcomes in at-risk populations. Therefore, the aim of our study was to assess the accuracy of REaL and gender identity data at our institution.

Lithium-Induced Bradycardia and Cardiomyopathy in a Patient With Bipolar Disorder and Paranoid Schizophrenia.

Lithium is primarily known to cause neurological and gastrointestinal side effects, however, cardiac effects have been rarely reported. We present a unique case of lithium cardiotoxicity causing bradyarrhythmia and cardiomyopathy. A 68-year-old man with a history of paranoid schizophrenia and bipolar disorder presented with altered mental status.

Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.

Transcription factors play a major role in regulation and orchestration of immune responses. The immunological context of the response can alter the regulatory networks required for proper functioning. While these networks have been well-studied in canonical immune contexts like infection, the transcription factor landscape during alloactivation remains unclear.

Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways.

Type 1 (T1D) or type 2 diabetes (T2D) are caused by a deficit of functional insulin-producing β cells. Thus, the identification of β cell trophic agents could allow the development of therapeutic strategies to counteract diabetes. The discovery of SerpinB1, an elastase inhibitor that promotes human β cell growth, prompted us to hypothesize that pancreatic elastase (PE) regulates β cell viability.

Associations Between Opioid Prescriptions and Use of Hospital-Based Services Among US Adults with Longstanding Physical Disability or Inflammatory Conditions Compared to Other Adults in the Medical Expenditure Panel Survey, 2010-2015.

Purpose: To investigate the association of filling opioid prescriptions with healthcare service utilization among a nationally representative sample of adults with disability.

Materials And Methods: The Medical Expenditure Panel Survey (MEPS) for 2010-2015, Panels 15-19, was used to identify adults who were prescribed opioids during each two-year period. We examined the data for associations between opioid prescription filling and the number of emergency department (ED) visits and hospitalizations.

NSC95397 is a Novel HIV-1 Latency Reversing Agent.

The latent viral reservoir represents one of the major barriers of curing HIV-1. Focus on the "kick and kill" approach, in which virus expression is reactivated then cells producing virus are selectively depleted, has led to the discovery of many latency reversing agents (LRAs) that have furthered our understanding of the mechanisms driving HIV-1 latency and latency reversal. Thus far, individual compounds have yet to be robust enough to work as a therapy, highlighting the importance of identifying new compounds that target novel pathways and synergize with known LRAs.

Liquid biopsies and minimal residual disease in lymphoid malignancies.

Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted.

A Rare Case of Skin Necrosis Following Extravasation of Prothrombin Complex Concentrate (PCC) Infusion During Warfarin Reversal.

Warfarin-induced skin necrosis is a well-documented complication that can occur following commencement of warfarin. However, skin necrosis following extravasation of prothrombin complex concentrate (PCC) infusion is a very rare adverse event that is not commonly documented. This case illustrates the possibility of developing skin necrosis following the administration of an anticoagulation reversal agent rather than from anticoagulation itself.

Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients.

Impact of Poorly Controlled Diabetes and Glycosylated Hemoglobin Values in Geriatric Hip Fracture Mortality Risk Assessment.

Introduction The presence of poorly-controlled diabetes in the setting of geriatric hip fractures has been shown to increase all-cause mortality and worsen outcomes. This study aimed to assess whether the addition of a patient's glycated hemoglobin (A1c) value to a validated geriatric inpatient risk tool improves the predictive capacity of the risk tool. Methods A cohort of 2430 patients >55 years old treated for low-energy mechanism hip fractures between October 2014 to November 2021 were reviewed for demographics (including diabetes diagnoses and their respective hemoglobin A1c values at the time of admission), injury details, hospital quality measures, and mortality.

Spontaneous Tumor Lysis Syndrome in a Patient With a Known History of Chronic Lymphocytic Leukemia Prior to Cytotoxic Chemotherapy.

Tumor lysis syndrome (TLS) is an oncological emergency resulting in an imbalance of electrolytes released upon tumor cell death leading to life-threatening acute renal failure. Typically, TLS is triggered by cytotoxic chemotherapy; however, it can rarely occur spontaneously. Our case report presents a patient with a known malignancy, but not on any cytotoxic chemotherapy, who presents to the emergency department with metabolic derangements suggestive of spontaneous TLS.

An Extremely Rare Case of Prostate and Bladder Wall Involvement of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and is characterized by monoclonal proliferation of B-cell lymphocytes which are morphologically mature, but immunologically dysfunctional. The primary sites of disease involvement include peripheral blood, lymph nodes, spleen, and bone marrow. CLL can also present locally and aggressively at extranodal sites.

Purification of human β- and γ-actin from budding yeast.

Biochemical studies of human actin and its binding partners rely heavily on abundant and easily purified α-actin from skeletal muscle. Therefore, muscle actin has been used to evaluate and determine the activities of most actin regulatory proteins but there is an underlying concern that these proteins perform differently from actin present in non-muscle cells. To provide easily accessible and relatively abundant sources of human β- or γ-actin (i.

Etiology and management of hypofibrinogenemia in trauma.

Purpose Of Review: Fibrin polymerization is essential for stable clot formation in trauma, and hypofibrinogenemia reduces hemostasis in trauma. This review considers fibrinogen biology, the changes that fibrinogen undergoes after major trauma, and current evidence for lab testing and treatment.

Recent Findings: Fibrinogen is a polypeptide that is converted to fibrin by the action of thrombin.

Hierarchical assembly of the MLL1 core complex regulates H3K4 methylation and is dependent on temperature and component concentration.

Enzymes of the mixed lineage leukemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases are critical for cellular differentiation and development and are regulated by interaction with a conserved subcomplex consisting of WDR5, RbBP5, Ash2L, and DPY30. While pairwise interactions between complex subunits have been determined, the mechanisms regulating holocomplex assembly are unknown. In this investigation, we systematically characterized the biophysical properties of a reconstituted human MLL1 core complex and found that the MLL1-WDR5 heterodimer interacts with the RbBP5-Ash2L-DPY30 subcomplex in a hierarchical assembly pathway that is highly dependent on concentration and temperature.

Glutamine metabolism and radiosensitivity: Beyond the Warburg effect.

Mounting data suggest that cancer cell metabolism can be utilized therapeutically to halt cell proliferation, metastasis and disease progression. Radiation therapy is a critical component of cancer treatment in curative and palliative settings. The use of metabolism-based therapeutics has become increasingly popular in combination with radiotherapy to overcome radioresistance.

Latest updates on cellular and molecular biomarkers of gliomas.

Gliomas are the most common central nervous system malignancies, compromising almost 80% of all brain tumors and is associated with significant mortality. The classification of gliomas has shifted from basic histological perspective to one that is based on molecular biomarkers. Treatment of this type of tumors consists currently of surgery, chemotherapy and radiation therapy.