Publications by authors named "Shulman D"

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations.

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Purpose: Novel therapies targeting specific genomic alterations are a promising treatment approach for relapsed/refractory cancer. Patients with specific alterations may be more likely to respond. Trial designs should maximize opportunities for such patients to enroll on these trials.

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Purpose: The fragility index (FI) is an adjunctive metric to facilitate the interpretation of p-values in clinical trials. The FI has not been studied in phase 3 trials in pediatric oncology.

Methods: PubMed was used to identify phase 3 pediatric oncology trials published between 1980 and 2020.

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Background: Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial.

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Background: Immune checkpoint inhibitors (ICI) have improved outcomes in a variety of adult cancers and are prescribed with increasing frequency across oncology. However, patterns of off-label use of ICI in pediatrics remain unclear.

Methods: This is a single-institution, retrospective cohort study evaluating off-label ICI use in pediatric and young adult patients with cancer treated at our institution from 2014 to 2022.

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In this paper, we investigate the potential of using a Michelson interferometer to measure the magnetic susceptibility of liquids. The theoretical basis for this measurement technique is presented, including the relevant equations and models used to analyze the data. The proposed method involves using a ring magnet to deform the liquid and passing a laser beam through the liquid to measure the resulting interference pattern using the interferometer.

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Background: Plaque incision/excision and grafting are surgical techniques used to treat patients with Peyronie's disease who are refractory to less invasive interventions, have severe penile curvature, or have an hourglass deformity. However, the procedure carries the risk of penile sensory loss because of the need for dissection of the neurovascular bundle (NVB). The aim of this study was to assess the feasibility of a novel technique for unilateral NVB dissection and its ability to preserve penile sensitivity while maintaining adequate correction of the penile curvature.

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Purpose: Osteosarcoma research advancement requires enhanced data integration across different modalities and sources. Current osteosarcoma research, encompassing clinical, genomic, protein, and tissue imaging data, is hindered by the siloed landscape of data generation and storage.

Materials And Methods: Clinical, molecular profiling, and tissue imaging data for 573 patients with pediatric osteosarcoma were collected from four public and institutional sources.

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Dual tasks requiring sustained visual attention and upright stance are common, yet their impact on standing balance is not well understood. We investigated the role of visual attention in the maintenance of postural control, using the multiple-object tracking (MOT) task. Healthy young adults ( = 12) performed the MOT task at three object movement speeds while seated or standing.

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This study presents a novel and user-friendly technique for detecting the lateral capillary force on a floating spherical particle. The technique leverages the interplay between the capillary attracting forces, hydrostatic pressure forces, and magnetic repulsion forces. A magnetic field is applied to induce a surface curvature in the liquid, resulting in a non-uniform distribution of capillary and hydrostatic pressure forces across the particle's surface.

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During MiniMed™ advanced hybrid closed-loop (AHCL) use by adolescents and adults in the pivotal trial, glycated hemoglobin (A1C) was significantly reduced, time spent in range (TIR) was significantly increased, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA). The present study investigated the same primary safety and effectiveness endpoints during AHCL use by a younger cohort with type 1 diabetes (T1D). An intention-to-treat population ( = 160, aged 7-17 years) with T1D was enrolled in a single-arm study at 13 investigational centers.

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Purpose: Phase 1 study assessing the safety and toxicity of cabozantinib in combination with topotecan and cyclophosphamide for relapsed osteosarcoma and Ewing sarcoma.

Methods: Oral cabozantinib (25 mg/m ) was administered daily for 21 (dose level 1) or 14 (dose level -1B) days. Topotecan (0.

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Purpose: Multitargeted tyrosine kinase inhibitors (mTKIs) are increasingly utilized in the treatment of pediatric sarcomas and other solid tumors. It is unknown whether serial treatment with multiple TKIs provides a benefit and which patients are most likely to benefit from mTKI rechallenge.

Methods: We performed a retrospective cohort study of pediatric cancer patients who received serial mTKI therapy off-study between 2007 and 2020 as either monotherapy or combination therapy.

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Background: Ewing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin-dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF-1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF-1R monoclonal antibody) for patients with relapsed EWS.

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Safety and significant improvement in overall glycated hemoglobin (A1C) and percentage of time spent in (TIR), below (TBR), and above (TAR) glucose range were demonstrated in the pivotal trial of adolescents and adults using the MiniMed™ advanced hybrid closed-loop (AHCL) system with the adjunctive, calibration-required Guardian™ Sensor 3. The present study evaluated early outcomes of continued access study (CAS) participants who transitioned from the pivotal trial investigational system to the approved MiniMed™ 780G system with the non-adjunctive, calibration-free Guardian™ 4 Sensor (MM780G+G4S). Study data were presented alongside those of real-world MM780G+G4S users from Europe, the Middle East, and Africa.

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Introduction: Females with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in transfer RNS (tRNA) fragments (tRFs) targeting cholinergic transcripts (CholinotRFs).

Methods: We analyzed small RNA-sequencing (RNA-Seq) data from the nucleus accumbens (NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation.

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Introduction: Females with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in tRNA fragments (tRFs) targeting cholinergic transcripts (CholinotRFs).

Methods: We analyzed small RNA-sequencing data from the (NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation.

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Transfer RNA fragments (tRFs) have recently been shown to be an important family of small regulatory RNAs with diverse functions. Recent reports have revealed modified tRF blood levels in a number of nervous system conditions including epilepsy, ischemic stroke, and neurodegenerative diseases, but little is known about tRF levels in the cerebrospinal fluid (CSF). To address this issue, we studied age, sex, and Parkinson's disease (PD) effects on the distributions of tRFs in the CSF and blood data of healthy controls and PD patients from the NIH and the Parkinson's Progression Markers Initiative (PPMI) small RNA-seq datasets.

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Background: Ewing sarcoma (EWS) is an aggressive sarcoma with no validated molecular biomarkers. We aimed to determine the frequency of STAG2 protein loss by immunohistochemistry (IHC) and whether loss of expression is associated with outcome.

Methods: We performed a retrospective cohort study of patients with EWS enrolled to Children's Oncology Group studies.

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The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60-80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects.

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Background: Synovial sarcoma (SS) accounts for 8%-10% of all soft-tissue sarcomas. Clinical presentation and outcomes vary, yet discrete risk groups based on validated prognostic indices are not defined for the full spectrum of patients with SS.

Methods: We performed a retrospective cohort study using data from the SEER (surveillance, epidemiology, and end results program) database of SS patients who were <70 years of age at diagnosis.

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Purpose: We sought to determine whether the detection of circulating tumor DNA (ctDNA) in samples of patients undergoing chemotherapy for advanced leiomyosarcoma (LMS) is associated with objective response or survival.

Experimental Design: Using ultra-low-passage whole-genome sequencing (ULP-WGS) of plasma cell-free DNA from patients treated on a prospective clinical trial, we tested whether detection of ctDNA evaluated prior to the start of therapy and after two cycles of chemotherapy was associated with treatment response and outcome. Associations between detection of ctDNA and pathologic measures of disease burden were evaluated.

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We report a successful pregnancy in a young woman with autosomal dominant hypoparathyroidism type 1 (ADH1) due to an activating mutation of the calcium sensing receptor (CASR) (c.2519C>T; p.Ala840Val) who was treated with recombinant human parathyroid hormone (rhPTH) delivered via continuous subcutaneous infusion using an OmniPod pump.

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Somatic gene translocations are key to making an accurate diagnosis in many cancers including many pediatric sarcomas. Currently available molecular diagnostic approaches to identifying somatic pathognomonic translocations have limitations such as minimal multiplexing, high cost, complex computational requirements, or slow turnaround times. We sought to develop a new fusion-detection assay optimized to mitigate these challenges.

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Climate change attributable to human activities has created a global threat to humanity and the natural world. However, there is a tendency for people to view climate change as a threat primarily affecting those in far-away places and there is reluctance to engage in pro-environmental action, which is often costly. It is therefore crucial to understand the factors that shape willingness to engage in pro-environmental behavior.

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