Publications by authors named "Levine R"

Dynamical symmetries, time-dependent operators that almost commute with the Hamiltonian, extend the role of ordinary symmetries. Motivated by progress in quantum technologies, we illustrate a practical algebraic approach to computing such time-dependent operators. Explicitly we expand them as a linear combination of time-independent operators with time-dependent coefficients.

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Pediatric high-grade gliomas (pHGG) and pediatric diffuse midline gliomas (pDMG) are devastating diseases without durable and curative options. Although targeted immunotherapy has shown promise, the field lacks immunocompetent animal models to study these processes in detail. To achieve this, we developed a fully immunocompetent, genetically engineered mouse model (GEMM) for pDMG and pHGG that incorporates the glioma-associated antigen, interleukin 13 receptor alpha 2 (IL13RA2).

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Background: Spatial repellent products are used for prevention of insect bites, and a body of evidence exists on spatial repellent entomological efficacy. A new option for vector control, spatial repellent products are designed to release active ingredient into the air for disruption of human-vector contact thereby reducing human exposure to mosquito-borne pathogens. Clinical trials have shown spatial repellent epidemiological efficacy against Aedes-borne viruses but inconclusive outcomes against malaria.

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Ca/calmodulin-dependent protein kinase II α (CaMKIIα) "autonomous" activation induced by Thr286 phosphorylation has a crucial role in synaptic plasticity. Previous studies showed that in Alzheimer's disease brain, CaMKIIα autophosphorylation at Thr286 is reduced while the level of cysteine-oxidized CAMKIIα is elevated. We performed tryptic mapping of the oxidized CaMKIIα and discovered the formation of a disulfide between the N-terminal Cys6 and the regulatory domain Cys280.

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Background: Gender inequity persists in high-level leadership within academic medicine. Understanding the perspectives of early career women faculty could clarify how to recruit and support women who pursue high-level leadership. This study explored the specific priorities and concerns that may influence the recruitment of women leaders in the future.

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Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

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Background: In the United States (US) and worldwide alcohol is a major contributor to premature mortality and morbidity. We explored US trends in alcohol related mortality from 1999 to 2020 overall and by age, gender, race, and region METHODS: Publicly available US Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) and the underlying cause of death file from CDC WONDER using ICD-10 codes.

Results: In 1999, there were 19,356 alcohol-related deaths, a mortality rate of 10.

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Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes.

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Article Synopsis
  • Researchers are merging unstructured patient data with structured health records to create the MSK-CHORD dataset, consisting of varied cancer types from nearly 25,000 patients at Memorial Sloan Kettering Cancer Center.
  • This dataset allows for in-depth analysis of cancer outcomes using advanced techniques like natural language processing, revealing new relationships that smaller datasets may not show.
  • Using MSK-CHORD for machine learning models, findings suggest that incorporating features from these unstructured texts can better predict patient survival than relying solely on genomic data or cancer staging.
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Background: Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved.

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BTX-A51, a first-in-class oral small molecule inhibitor of casein kinase 1α (CK1α) and cyclin dependent kinase (CDK) 7 and 9, induces apoptosis of leukemic cells by activating p53 and inhibiting expression of . Here, we report on the results of the phase 1 clinical trial of BTX-A51 in patients with relapsed or refractory AML and MDS. Thirty-one patients were enrolled into 8 dose-escalation cohorts at BTX-A51 doses ranging from 1mg to 42mg dosed three days/week for 21 or 28 days out a 28-day cycle.

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Article Synopsis
  • * Hematologic cancers, unlike solid tumors, generally have fewer genetic mutations, making their study more complicated due to their complex microenvironment.
  • * Focusing on external factors is vital for preventing myeloid malignancies, especially in older patients with poor prognoses, and can help identify effective interventions and predict outcomes.
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  • Hyperglycemia in diabetes leads to the buildup of Advanced glycation end products (AGEs), which is linked to cardiovascular issues via their impact on cholesterol levels.
  • The study investigated how plasma from poorly controlled adolescents with type 1 diabetes affects cholesterol handling in human macrophages, using THP-1 cells in a lab setting.
  • Findings revealed that T1D plasma increased certain proteins related to cholesterol uptake and foam cell formation, suggesting that AGEs exacerbate atherosclerosis in diabetes by disrupting cholesterol transport processes.
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Anaplastic thyroid cancer (ATC) is a clinically aggressive malignancy with a dismal prognosis. Combined BRAF/MEK inhibition offers significant therapeutic benefit in patients with -mutant ATCs. However, relapses are common and overall survival remains poor.

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Article Synopsis
  • * The study analyzed data from 1,189 patients to assess how severe MR affects outcomes like mortality and heart complications, finding that those with severe MR faced worse health risks over a five-year period.
  • * Results indicated that severe MR significantly increased the risk of mortality and the need for aortic valve replacement (AVR), but AVR greatly improved survival rates, particularly in patients with severe MR.
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Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected.

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Dental implants are a reliable treatment option for restoring missing teeth, but adequate bone quantity and quality are crucial for success. This case series presents four cases treated by different clinicians, all following very similar concepts for combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB. All cases involved a severe periodontal defect requiring either extraction of the adjacent tooth or periodontal regeneration.

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Aims: Rheumatic mitral stenosis (MS) frequently leads to impaired left atrial (LA) function because of pressure overload, highlighting the underlying atrial pathology. Two-dimensional speckle tracking echocardiography (2D-STE) offers early detection of LA dysfunction, potentially improving risk assessment in patients with MS. This study aims to evaluate the predictive value of LA function assessed by 2D-STE for clinical outcomes in patients with MS.

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Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells.

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Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells.

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Impostor phenomenon (IP) describes feelings of inadequacy often experienced by individuals struggling to internalize success despite evidence to the contrary. IP is common in medicine and can be experienced as a cycle following exposure to an achievement-focused task, leading to fear of being found out as an impostor. Prior research describes IP characteristics, yet few studies have identified factors that mitigate IP among medical residents.

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Article Synopsis
  • The European LeukemiaNet (ELN) previously created genetic risk classifications using data from younger adults who underwent intensive chemotherapy.
  • New research has emerged analyzing patients who receive less-intensive therapies, highlighting the need for tailored classifications.
  • This has led to a proposal for a new ELN genetic risk classification specifically designed for patients undergoing these alternative treatment options.
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  • Chemotherapy often leads to side effects that can negatively affect treatment outcomes, while exercise during treatment has shown benefits for physical functioning and mental health, but its impact on clinical outcomes like chemotherapy dose intensity is uncertain.
  • The ENICTO Consortium, funded by the National Cancer Institute, aims to fill this knowledge gap by exploring how exercise and nutrition may improve chemotherapy-related outcomes and detailing distinct research projects within their framework.
  • The findings from ENICTO could change oncology care practices, making exercise and nutrition support a standard part of cancer treatment alongside chemotherapy to enhance overall effectiveness and patient outcomes.
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