Publications by authors named "Silberstein J"

Serological and histological examinations have unveiled the presence of free β subunit of human chorionic gonadotropin (β-hCG) in some cases of colorectal adenocarcinoma. The present study describes an unusual case of a young female patient afflicted with rapidly advancing adenocarcinoma of the sigmoid colon. Despite the absence of pregnancy indications on an ultrasound and curettage, a notable elevation of β-hCG was detected in the serum, alongside positive staining in the tumor tissue.

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Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function.

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This study aimed to determine the diagnostic yield of singleton exome sequencing and subsequent research-based trio exome analysis in children with a spectrum of brain malformations seen commonly in clinical practice. We recruited children ≤ 18 years old with a brain malformation diagnosed by magnetic resonance imaging and consistent with an established list of known genetic causes. Patients were ascertained nationally from eight tertiary paediatric centres as part of the Australian Genomics Brain Malformation Flagship.

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The use of low-cost sensors (LCSs) for the mobile monitoring of oil and gas emissions is an understudied application of low-cost air quality monitoring devices. To assess the efficacy of low-cost sensors as a screening tool for the mobile monitoring of fugitive methane emissions stemming from well sites in eastern Colorado, we colocated an array of low-cost sensors (XPOD) with a reference grade methane monitor (Aeris Ultra) on a mobile monitoring vehicle from 15 August through 27 September 2023. Fitting our low-cost sensor data with a bootstrap and aggregated random forest model, we found a high correlation between the reference and XPOD CH concentrations (r = 0.

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Cardiovascular CT is being widely used in the diagnosis of cardiovascular disease due to the rapid technological advancements in CT scanning techniques. These advancements include the development of multi-slice CT, from early generation to the latest models, which has the capability of acquiring images with high spatial and temporal resolution. The recent emergence of photon-counting CT has further enhanced CT performance in clinical applications, providing improved spatial and contrast resolution.

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Article Synopsis
  • Osteoporotic vertebral fractures (OVFs) often go undetected in chest radiographs, especially in post-menopausal women over 60, necessitating an effective detection tool.
  • The study evaluated the AI tool Ofeye 1.0's performance in identifying OVFs on lateral chest x-rays, finding that it detected missed fractures in 28.8% of cases and had improved sensitivity compared to original radiologist reports.
  • While Ofeye 1.0 showed high specificity (92.8%) and moderate overall accuracy (80.3%), its lower sensitivity (49%) indicates it should be used as a complementary tool alongside traditional radiology.
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Three-dimensional (3D) printing plays an important role in cardiovascular disease through the use of personalised models that replicate the normal anatomy and its pathology with high accuracy and reliability. While 3D printed heart and vascular models have been shown to improve medical education, preoperative planning and simulation of cardiac procedures, as well as to enhance communication with patients, 3D bioprinting represents a potential advancement of 3D printing technology by allowing the printing of cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large-scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs.

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  • Early mortality in multiple myeloma is a significant issue, particularly affecting older adults, with an overall rate of 8.3% in a study of patients treated in community oncology practices.
  • The study analyzed 7512 newly diagnosed patients, identifying key predictors of early mortality such as age ≥70 years, poor performance status (ECOG PS ≥ 2), advanced disease stage (R-ISS stage III), and renal dysfunction.
  • The findings highlight the need for targeted interventions aimed at older patients to improve survival rates and address the disparities in outcomes.
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Introduction: This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period.

Patients And Methods: All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database.

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We report a female child with PCDH19 related developmental and epileptic encephalopathy with drug-resistant seizures, cognitive and language impairment, autism spectrum disorder and sleep dysfunction. Her seizures, which started at 10 months of age, were resistant to multiple anti-seizure medications. Developmental stagnation followed by regression occurred after the onset of recurrent seizures.

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Background: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended.

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Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS).

Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer.

Design, Setting, And Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites.

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Adoptive cell therapy is a rapidly advancing approach to cancer immunotherapy that seeks to facilitate antitumor responses by introducing potent effector cells into the tumor microenvironment. Expanded autologous T cells, particularly T cells with engineered T cell receptors (TCR) and chimeric antigen receptor-T cells have had success in various hematologic malignancies but have faced challenges when applied to solid tumors. As a result, other immune subpopulations may provide valuable and orthogonal options for treatment.

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Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS.

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Background: Altered DNA damage response (DDR) has emerged as an important mechanism for the development of aggressive prostate cancer among men of European ancestry but not other ancestry groups. Because common mechanisms for aggressive disease are expected, we explored a large panel of DDR genes and pathways to demonstrate that DDR alterations contribute to development of aggressive prostate cancer in both African American and European American men.

Methods: We performed a case-case study of 764 African American and European American men with lethal or indolent prostate cancer treated at 4 US hospitals.

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The disialoganglioside GD2 is overexpressed on several solid tumors, and monoclonal antibodies targeting GD2 have substantially improved outcomes for children with high-risk neuroblastoma. However, approximately 40% of patients with neuroblastoma still relapse, and anti-GD2 has not mediated significant clinical activity in any other GD2 malignancy. Macrophages are important mediators of anti-tumor immunity, but tumors resist macrophage phagocytosis through expression of the checkpoint molecule CD47, a so-called 'Don't eat me' signal.

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African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions; however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection.

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity.

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Objective: To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear.

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V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint that maintains peripheral T cell quiescence and inhibits anti-tumor immune responses. VISTA functions by dampening the interaction between myeloid cells and T cells, orthogonal to PD-1 and other checkpoints of the tumor-T cell signaling axis. Here, we report the use of yeast surface display to engineer an anti-VISTA antibody that binds with high affinity to mouse, human, and cynomolgus monkey VISTA.

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Introduction: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are useful clinical biomarkers for prognosis in several malignancies. Their predictive value has been less clearly demonstrated with prostate cancer (PCa), particularly, their utility within active surveillance (AS) protocols. We aim to evaluate NLR and PLR in AS patients.

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Background: Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized.

Materials And Methods: A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p<0.

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Background: Most pediatric elevated blood pressure (BP) remains undiagnosed. The American Academy of Pediatrics states "there is limited evidence to support school-based measurement of children's BP." We explored the utility school-based BP screening.

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