Publications by authors named "Ortiz Michael"

Background: Complicated mild traumatic brain injury (cmTBI) is a common neurosurgical disorder that consumes a significant amount of healthcare resources without a clearly established benefit. Best practices for the management of cmTBI regarding triage, hospital admission, and the necessity for repeat imaging are controversial. Our objective is to describe the rate of radiographic progression and neurologic decline for isolated traumatic subarachnoid hemorrhage (itSAH) patients admitted to the hospital.

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ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

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The treatment of spinal pathologies has evolved significantly from the times of Hippocrates and Galen to the current era. This evolution has led to the development of cutting-edge technologies to improve surgical techniques and patient outcomes. The University of Missouri Health System is a high-volume, tertiary care academic medical center that serves a large catchment area in central Missouri and beyond.

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Purpose: To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST).

Methods: A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery.

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We present a class of model-free Data-Driven solvers that effectively enable the utilization of in situ and in vivo imaging data directly in full-scale calculations of the mechanical response of the human brain to sonic and ultrasonic stimulation, entirely bypassing the need for analytical modeling or regression of the data. The well-posedness of the approach and its convergence with respect to data are proven analytically. We demonstrate the approach, including its ability to make detailed spatially resolved patient-specific predictions of wave patterns, using public-domain MRI images, MRE data and commercially available solid-mechanics software.

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Background: The optimal target post-procedure stenosis after percutaneous angioplasty and stent placement (PTAS) for intracranial stenosis is unknown. We determined the effect of post-procedure stenosis after intracranial PTAS on subsequent clinical events in patients with severe symptomatic intracranial stenosis.

Methods: We categorized the severity of post-procedure stenosis as '<30%', '30-49%', and '≥50%' among 207 patients who underwent PTAS in a multicenter randomized clinical trial.

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Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer.

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The small-molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities in adults and children. Its preclinical antitumor activity in pediatric malignancies, however, is largely unknown. We here assessed the preclinical activity of elimusertib in 38 cell lines and 32 patient-derived xenograft (PDX) models derived from common pediatric solid tumor entities.

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Article Synopsis
  • - The study of Wilms tumour, which began with Alfred Knudson's 'two-hit' model, has advanced significantly over the last 50 years, leading to important discoveries in its genetics and biology.
  • - Research has focused on identifying prognostic biomarkers to improve treatment outcomes, although variability in these biomarkers within tumors creates challenges for individual patient care.
  • - Despite progress, ongoing investigations aim to deepen molecular understanding of Wilms tumour, including causes of relapse and bilateral cases, with international collaboration being key to addressing these complex issues.
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Unlabelled: Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma.

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Article Synopsis
  • DNA damage response inhibitors could be really helpful in treating childhood cancers, but we still need to figure out the best way to use them and who should get them.
  • There aren't many kids with cancer to test these drugs, which makes it tricky to find the right way to prioritize their use in treatments.
  • Some specific types of drugs, like CHK1 inhibitors, show promise for certain pediatric tumors and should be made available for trials quickly.
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During infections with the malaria parasites , patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock [Rijo-Ferreira, , 746-753 (2020); Smith .

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Article Synopsis
  • - Wilms tumors (WT) have excellent outcomes for most patients, but certain high-risk subgroups have survival rates around 50% or less.
  • - The classification of high-risk WT has evolved over time, now including patients with metastatic or poorly differentiated types, those who relapse after extensive treatment, and socio-economically disadvantaged groups in lower income settings.
  • - Conventional treatments are often insufficient for high-risk WT patients, making it crucial to advance research into new therapies through laboratory and early-phase clinical trials.
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Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

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Multiple large-scale tumor genomic profiling efforts have been undertaken in osteosarcoma, however, little is known about the spatial and temporal intratumor heterogeneity and how it may drive treatment resistance. We performed whole-genome sequencing of 37 tumor samples from eight patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site.

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Article Synopsis
  • The majority of patients with Wilms tumors (WT) have excellent outcomes, but certain high-risk subgroups have survival rates of around 50% or lower.
  • The classification of high-risk WT has evolved due to improvements in treatment, now including various types of metastatic tumors and those with multiple relapses.
  • There is an urgent need for research into new active treatments for high-risk WT patients, especially in low-resource settings where socio-economic factors can further impact survival rates.
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Background: Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.

Methods: Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity.

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SMARCB1 biallelic inactivation resulting in SMARCB1/INI1 deficiency drives a wide range of malignancies, including many mesenchymal tumors. However, the specific types of SMARCB1 alterations and spectrum of cooperating mutations among various types of sarcomas has not been well investigated. We profiled SMARCB1 genetic alterations by targeted DNA sequencing and fluorescence in situ hybridization (FISH) in a large cohort of 118 soft tissue and bone tumors, including SMARCB1-deficient sarcomas (78, 66%): epithelioid sarcomas, epithelioid peripheral nerve sheath tumors, poorly differentiated chordomas, malignant rhabdoid tumors, and soft tissue myoepithelial tumors, as well as non-SMARCB1-deficient sarcomas (40, 34%) with various SMARCB1 genetic alterations (mutations, copy number alterations).

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Acoustic reporter genes based on gas vesicles (GVs) have enabled the use of ultrasound to noninvasively visualize cellular function in vivo. The specific detection of GV signals relative to background acoustic scattering in tissues is facilitated by nonlinear ultrasound imaging techniques taking advantage of the sonomechanical buckling of GVs. However, the effect of geometry on the buckling behavior of GVs under exposure to ultrasound has not been studied.

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