3,620 results match your criteria: "FL ∥University of Pennsylvania[Affiliation]"

Article Synopsis
  • Dystonia is a common movement disorder with a complex genetic background, showing significant variability in its clinical presentation and genetics.
  • The study involved exome sequencing of nearly 1,924 patients, mainly from two major registries, focusing on those with genetic prescreening negative results and early age at onset.
  • Researchers discovered 137 likely pathogenic variants in 51 genes among the patients, with many being novel, highlighting the challenges in diagnosing and understanding the disorder's genetic links.
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Background: Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory/immune mechanisms are induced by TSE, play a key role in the recovery process versus development of post-TSE chronic pain, and are sex specific. In this study, we tested the hypothesis that the inflammatory marker C-reactive protein (CRP) is associated with chronic pain after TSE in a sex-specific manner.

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Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration.

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Purpose: This study developed and validated a novel deep learning radiomic biomarker to estimate response to immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) using real-world data (RWD) and clinical trial data.

Materials And Methods: Retrospective RWD of 1,829 patients with advanced NSCLC treated with PD-(L)1 ICIs were collected from 10 academic and community institutions in the United States and Europe. The RWD included data sets for discovery (Data Set A-Discovery, n = 1,173) and independent test (Data Set B, n = 458).

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Article Synopsis
  • The study investigates the genetic variance (variome) of the Turkish population, focusing on how admixture and consanguinity influence their genomic makeup related to diseases.
  • Exome sequencing data from 773 affected individuals and 643 unaffected relatives revealed that Turkish genomes are closely related to Europeans, with two main subpopulations showing different levels of genetic mixing.
  • The analysis identified that higher inbreeding coefficients and longer runs of homozygosity in affected individuals are linked to rare harmful genetic variants, emphasizing their role in hereditary diseases within this population.
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The precise mechanisms by which the complement system contributes to the establishment of an immunosuppressive tumor microenvironment (TME) and promotes tumor progression remain unclear. In this study, we investigated the expression and function of complement C5a receptor 1 (C5aR1) in human and mouse cancer-associated dendritic cells (DCs). First, we observed an overexpression of C5aR1 in tumor-infiltrating DCs, compared to DCs from blood or spleen.

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Introduction: Service academy members are at high risk for concussions as a result of participation in both sports and military-specific training activities. Approximately 17% of active duty service members are female, and they face unique challenges in achieving timely recovery from concussions. Understanding the unique characteristics affecting return to unrestricted activity (RTA) among female service academy members is imperative for the ever-growing proportion of females across the U.

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Widespread distribution of transduced brain cells following delivery of AAV vectors into the cerebrospinal fluid (CSF) of the cisterna magna (CM) has been demonstrated in large animal brains. In humans, intraventricular injection is preferred to intracisternal injection for CSF delivery due to the risk of brain stem injury. One study in the dog reported adverse reactions to AAV vectors expressing GFP injected into the lateral ventricle but not when injected into the CM.

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Current State of Community-Driven Radiological AI Deployment in Medical Imaging.

JMIR AI

December 2024

Clinical Scientific Computing, Medical Physics, Newton's Tree, London, United Kingdom.

Artificial intelligence (AI) has become commonplace in solving routine everyday tasks. Because of the exponential growth in medical imaging data volume and complexity, the workload on radiologists is steadily increasing. AI has been shown to improve efficiency in medical image generation, processing, and interpretation, and various such AI models have been developed across research laboratories worldwide.

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Purpose: The TRK inhibitor larotrectinib is US Food and Drug Administration approved for fusion-positive solid tumors that lack a satisfactory alternative or have progressed after treatment but has not been systematically studied as a frontline therapy with a defined duration of treatment. ADVL1823 evaluated larotrectinib in patients with newly diagnosed fusion-positive solid tumors with response-adapted duration of therapy and local control.

Methods: Patients received larotrectinib twice daily in 28-day cycles for a predefined duration of treatment, ranging from 6 to 26 cycles depending on response to therapy and surgical resectability.

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A Guideline-Directed Approach to Obesity Treatment.

Diabetes Spectr

November 2024

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

This article summarizes and compares 18 sets of guidelines for adult obesity treatment, highlighting key recommendations for patient evaluation, lifestyle intervention, anti-obesity medications (AOMs), and metabolic and bariatric surgery. Guidelines are consistent in many regards, although there is divergence regarding preferred AOMs. Metabolic and bariatric surgery is still recognized as the most durable form of obesity treatment, and newer guidelines suggest these procedures at lower BMI thresholds for people with uncontrolled type 2 diabetes.

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Background: Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to genetic evaluations will enable strategies to enhance precision medicine care.

Methods: An online survey was conducted in June 2024 among cardiologist investigators of the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs to collect demographics, training, program characteristics, genetic evaluation practices for DCM, and implementation needs.

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Article Synopsis
  • This study analyzed decisions regarding decompressive hemicraniectomy (DHC) and early withdrawal of life-sustaining therapy (WLST) in patients with large vessel occlusion (LVO) and large ischemic strokes from the SELECT2 trial.* -
  • Among 352 patients, DHC was utilized in 55 patients, and WLST was chosen for 81, showing no significant differences in usage between those receiving endovascular thrombectomy (EVT) and those treated medically.* -
  • About 21% of DHC patients were able to walk independently after one year, indicating that DHC did not negatively impact the benefits of thrombectomy, while WLST generally resulted in poor outcomes.*
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Article Synopsis
  • The text discusses the importance of forecasting future health issues in the USA for effective planning and public awareness regarding disease and injury burdens.
  • It describes the methodology for predicting life expectancy, cause-specific mortality, and disability-adjusted life-years (DALYs) from 2022 to 2050 using the Global Burden of Diseases framework.
  • The forecasting includes various scenarios to assess the potential impacts of health risks and improvements across the country, focusing on demographic trends and health-related risk factors.
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This article reviews the psychological distress experienced by NICU families, including anxiety, postpartum depression (PPD), and post-traumatic stress disorder (PTSD), in addition to providing recommendations for clinicians at the individual, institutional, and national level. Currently, mental health screenings, specialized evaluations, and treatment options are not routinely offered to NICU families and are frequently under-utilized when offered. Here we provide expert opinion recommendations to address challenges in supporting universal screening, offering bedside interventions, including trained mental health professionals in care plans, updating neonatology training competencies, and advocating for policies that support the mental health of NICU families.

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EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function.

Cancer Cell

January 2025

Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address:

T cell-based immunotherapies have demonstrated effectiveness in treating diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) but predicting response and understanding resistance remains a challenge. To address this, we developed syngeneic models reflecting the genetics, epigenetics, and immunology of human FL and DLBCL. We show that EZH2 inhibitors reprogram these models to re-express T cell engagement genes and render them highly immunogenic.

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Background: Spetzler-Martin (SM) Grade III brain arteriovenous malformations (BAVMs) represent a transitional risk zone between low- and high-grade BAVMs, characterized by diverse angioarchitecture. The primary treatment options are endovascular embolization, microsurgical resection (MS), and stereotactic radiosurgery (SRS). This study compares the efficacy and outcomes of MS and SRS.

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Neurodevelopmental disorders are thought to arise from intrinsic brain abnormalities. Alternatively, they may arise from disrupted crosstalk among tissues. Here we show the local reduction of two vestibulo-cerebellar lobules, the paraflocculus and flocculus, in mouse models and humans with 22q11.

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Article Synopsis
  • - In the last decade, significant advancements have been made in treating adults with newly diagnosed B-cell acute lymphoblastic leukaemia, driven by better understanding of the disease and innovative treatment strategies like incorporating immunotherapy and tyrosine kinase inhibitors.
  • - Despite these advancements, adults still have worse outcomes compared to children, facing higher rates of treatment failure and complications, leading to ongoing use of transplant consolidation for high-risk cases.
  • - The article emphasizes the need for new trial designs to further improve treatment strategies and personalize care for adults with acute lymphoblastic leukaemia, sharing insights from practices across Europe and other continents.
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X-chromosome-wide association study for Alzheimer's disease.

Mol Psychiatry

December 2024

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France.

Article Synopsis
  • A study was conducted to investigate the X-chromosome's role in Alzheimer's Disease (AD), which had been overlooked in previous genome-wide association studies.
  • The research included 115,841 AD cases and 613,671 controls, considering different X-chromosome inactivation (XCI) states in females.
  • While no strong genetic risk factors for AD were found on the X-chromosome, seven significant loci were identified, suggesting areas for future research.
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Most homicides in the United States are committed using a handgun, but little research examines gun carrying over critical stages of the life course and changing contexts of violence. Notably, although most of the handgun homicides are committed by adults, most research on concealed gun carrying focuses on adolescents in single cohort studies. Using more than 25 years of longitudinal multicohort data from Chicago, 1994-2021, we show that pathways of concealed gun carrying are distinct between adolescence and adulthood.

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Article Synopsis
  • The outpatient continuity clinic is vital for internal medicine residency training, and the Primary Care Exception Rule (PCER) allows indirect supervision of residents during less complex patient visits.
  • The existing literature on the effects of the PCER is limited, yet it raises questions about its impact on patients, residents, attending physicians, and health systems.
  • Recommendations include avoiding PCER for critical diagnosis situations, advocating for competency-based supervision, and expanding the PCER to cover moderate-complexity visits, along with a call for further research in this area.
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Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status.

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