tbuckley/cabot-search huggingface dataset:
NIMG-19. USING FUNCTIONAL ULTRASOUND (FUS) TO MAP BRAIN FUNCTIONALITY AND TUMOR VASCULATURE WITH MICROMETER-MILLISECOND PRECISION
Authors: Sadaf Soloukey, Arnaud J P E Vincent, Djaina D Satoer, Frits Mastik, Marion Smits, Clemens M F Dirven, Christos Strydis, Antonius F W van der Steen, Johannes G Bosch, Chris I De Zeeuw, Sebastiaan K E Koekkoek, Pieter Kruizinga
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE In the early 20th century, Dr. Cushing first demonstrated the use of electrical stimulation mapping (ESM) to define motor and sensory cortices during neurosurgical procedures. Essentially, little has changed in what guides a neurosurgeon’s intra-operative decision-making since. Inherent limitations of ESM such as limited depth penetration and risk of seizure elicitation, warrant the development of new image-guided resection tools. Here, we present functional Ultrasound (fUS)-imaging as a new, high-resolution tool to guide intra-operative decision-making during awake tumor removal. METHODS fUS relies on high-frame-rate ultrasound, which offers images at thousands of frames-per-second. As such, fUS is sensitive to very small motions caused by vascular dynamics (µDoppler), allowing measurements of changes in cerebral blood volume (CBV). This facilitates the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling and 2) visualize high-resolution vascular morphology of tumor and healthy tissue. During conventional awake craniotomy surgery, n= 10 patients were asked to perform 60s functional tasks to elicit cortical responses. Simultaneously, a conventional 5 MHz ultrasound probe connected to an experimental acquisition system, was placed over ESM-defined functional areas. After image acquisition, correlation analyses with the corresponding tasks revealed functional and non-functional areas. In addition, 3D vascular maps were reconstructed from subsequent 2D-Power Doppler Images (PDIs). RESULTS fUS was able to detect functional areas as activated using conventional motor tasks, as well as complex language-related tasks. In addition, both 2D-PDIs and 3D-reconstructions revealed the ability of fUS to detect unique high-resolution onco-vascular characteristics in high- and low-grade malignancies. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5-2.0 msec) precision at imaging depths &amp;gt; 5 cm. CONCLUSIONS Applying fUS-imaging successfully in this awake craniotomy series serves as a clear demonstration of the technique’s revolutionary potential for maximizing safe tumor removal.
Lipid-laden Macrophages Are Not Unique to Patients with E-Cigarette or Vaping Product Use–associated Lung Injury
Authors: Arunava Ghosh, Saira Ahmad, Raymond D. Coakley, M. Flori Sassano, Neil E. Alexis, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Lipid-laden Macrophages Are Not Unique to Patients with E-Cigarette or Vaping Product Use–associated Lung Injury." American Journal of Respiratory and Critical Care Medicine, 203(8), pp. 1030–1033
BIOM-63. DIAGNOSIS AND PROGNOSTIC SIGNIFICANCE OF CIRCULATING miR-2276-5p IN PLASMA OF GLIOMA PATIENTS
Authors: Shiguang Zhao
Journal: Neuro-Oncology (2020)

Abstract Circulating microRNAs (miRNAs) in plasma have the potential to become diagnostic and prognostic biomarkers for various cancers. This study hopes to use plasma circulating miRNAs as biomarkers for diagnosis and prognosis of glioma patients. METHOD: In this study, the plasma circulating miRNAs of 124 patients with glioma and 36 controls was collected to detect the relative expression of miR-2276-5p, and the specificity and sensitivity of the diagnosis were verified by ROC curve. The follow-up survival status was analyzed by cox regression analysis. RESULT: In the GSE 139031 database, it was found that the expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of patients with non-gliomas. Using our plasma samples, and it is indicated that the expression of circulating miR-2276-5p in plasma is lower than that of healthy patients, and compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. ROC curve analysis found that the AUC value was 0.851. The low expression of circulating miR-2276-5p in plasma of glioma patients indicates a poor prognosis of glioma patients, After univariate and multifactorial cox regression analysis, which can be used as an independent prognostic risk factor for glioma patients (P&amp;lt; 0.05). CONCLUSION: The expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of the control group, compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. The lower the relative expression of circulating miR-2276-5p indicated that glioma patients had a worse prognosis.
Adjuvant Capecitabine in Triple-Negative Breast Cancer
Authors: Heather A. Parsons, Harold J. Burstein
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 10918: Home Healthcare Post-discharge Outcomes After Heart Failure Hospitalization: An American Heart Association Get With the Guidelines-heart Failure Study
Authors: Madeline R Sterling, Monika M Safford, Lisa M Kern, Christine D Jones, Penny H Feldman, Gregg C Fonarow, Shubin Sheng, Roland Matsouaka, Adam D Devore, Barbara Lytle, Larry A Allen, Anita M Deswal, Clyde W Yancy, Nancy M Albert
Journal: Circulation (2019)

Introduction: After hospitalization for heart failure (HF), some patients receive home healthcare (HHC) services; however, factors associated with use and outcomes are not well studied. Objective: ...
Mechanical Complications of Acute Myocardial Infarction
Authors: Fei Fei Gong, Inga Vaitenas, S. Chris Malaisrie, Kameswari Maganti
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Mechanical complications of acute myocardial infarction include left ventricular free-wall rupture, ventricular septal rupture, papillary muscle rupture, pseudoaneurysm, and true aneurysm. With the introduction of early reperfusion therapies, these complications now occur in fewer than 0.1% of patients following an acute myocardial infarction. However, mortality rates have not decreased in parallel, and mechanical complications remain an important determinant of outcomes after myocardial infarction. Early diagnosis and management are crucial to improving outcomes and require an understanding of the clinical findings that should raise suspicion of mechanical complications and the evolving surgical and percutaneous treatment options. <h3>Observations</h3> Mechanical complications most commonly occur within the first week after myocardial infarction. Cardiogenic shock or acute pulmonary edema are frequent presentations. Echocardiography is usually the first test used to identify the type, location, and hemodynamic consequences of the mechanical complication. Hemodynamic stabilization often requires a combination of medical therapy and mechanical circulatory support. Surgery is the definitive treatment, but the optimal timing remains unclear. Percutaneous therapies are emerging as an alternative treatment option for patients at prohibitive surgical risk. <h3>Conclusions and Relevance</h3> Mechanical complications present with acute and dramatic hemodynamic deterioration requiring rapid stabilization. Heart team involvement is required to determine appropriate management strategies for patients with mechanical complications after acute myocardial infarction.
TBIO-24. USING MOLECULAR GUIDED THERAPY IN PEDIATRIC NEURO ONCOLOGY PATIENTS: THE SUCCESS AND BARRIERS
Authors: Beth Armstrong, Morgan Schmitt, Jayne VonBergen
Journal: Neuro-Oncology (2020)

Abstract Remarkable advances have been made in pediatric brain tumor treatments, however many of these children suffer significant side effects from standard chemotherapy-based treatment. Recent advances in precision medicine offer great hope to pediatric patients in terms of improved therapeutic precision, safety, and efficacy. However, there are barriers to implementing precision medicine that are best approached from a multi-disciplinary perspective. The goals of the Riley Hospital for Children at Indiana University Health Precision Genomics Neuro Oncology program are to optimize the treatment of children by assessing children’s cancers for actionable molecular targets and finding available, affordable therapies that treat those actionable targets. Children are referred to the Riley Precision Genomics Neuro Oncology program at the time of diagnosis or with relapse. Tumor tissue is tested for somatic and germline findings. Riley’s Precision Genomics Neuro Oncology program has received 55 patient referrals. Of these 55 patients, 46 (84%) had molecular analysis completed, and the results of 40 (87%) patients indicated actionable targets. Of the 40 patients with results, 23 (58%) patients went on to receive genomics guided therapy. Limited availability of tissue has accounted for 6 (13%) patients’ lack of results. Many guided therapy options are oral medications, which positively impact patient’s quality of life. The learner will increase their knowledge of how molecular guided therapy is now innovatively being used to treat children with cancer, and the challenges involved.
Are Methods for Evaluating Medications Appropriate for Evaluating Nonpharmacological Treatments for Pain?—Challenges for an Emerging Field of Research
Authors: Daniel C. Cherkin
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 13206: Early Captopril Treatment Mitigates Doxorubicin Cardiomyopathy in Mice: A Cardiac MRI Pilot Study
Authors: George M Cater, Samuel K Wyman, Nathan Salamacha, Ryan Marsden, Shanim Manzoor, Brendan Sestokas, Erik B Schelbert, Timothy C Wong, Yijen L Wu
Journal: Circulation (2019)

Introduction: Use of angiotensin converting enzyme inhibitors (ACEi) for the primary prevention of anthracycline cardiomyopathy (ACM) remains controversial. Prior clinical studies use isolated meas...
Differential expression of PACS-1 in normal versus cervical tumor tissue
Authors: Mysore S. Veena, Rita Chakrabarthi, Kayvan Zainabadi, Leslie J. Redpath, Eric J. Stanbridge, Gary Thomas, Eri S. Srivatsan
Journal: Cancer Research (2005)

5454  Cervical cancer is one of the leading causes of female death worldwide with approximately 500,000 deaths per year. Recent micorsatellite studies on HeLa (a cervical cancer cell line), HeLa cell derived non-tumorigenic and tumorigenic hybrids and primary tumors have localized a putative tumor suppressor gene to a 300 kb interval of chromosome 11q13, between markers D11S4908 and D11S5023. This locus encompasses a 5.7 kb homozygous deletion in a primary tumor, in HeLa cells and in HeLa cell derived tumorigenic hybrids. It is likely that, this homozygous deletion locus represents sequences of the tumor suppressor gene. At least eleven known genes are mapped to this region. One of the genes, Phosphofurin acidic cluster sorter-1 (PACS-1), encodes a protein which has been implicated in intracellular vesicular trafficking of proteins such as furin and mannose-6-phosphate receptor. Northern blot studies with PACS-1 probe showed the presence of an aberrant 8 kb transcript in addition to the expected 4.5 kb messenger in cancer cell lines. Western blotting of normal and cervical tumor tissues using a PACS-1 antibody showed a major protein band of 125 KD in normal and tumor tissues. The tumor samples however contained an additional 114KD protein. The differences between normal and tumor cervical tissues indicate a possible splice variation, mutation, and/or post-translational modification that might play an important role in the development of cervical cancer.
EPEN-07. PATTERNS OF EXTRANEURAL METASTASES IN PEDIATRIC SUPRATENTORIAL EPENDYMOMA: CASE SERIES AND REVIEW OF THE LITERATURE
Authors: Priya P Chan, Nicholas S Whipple, Arie Perry, David A Solomon, Holly Zhou, Luke L Linscott, John R W Kestle, Carol Bruggers
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Ependymomas account for 10% of all malignant pediatric intracranial tumors. Standard therapy includes maximal safe surgical resection followed by involved-field radiation. Up to 50% of localized pediatric ependymomas recur. Extraneural metastases at time of recurrence are rarely reported. OBJECTIVE To describe extraneural metastases of pediatric ependymomas. METHODS Retrospective review of patients’ medical records and literature review. RESULTS Three patients with history of locally recurrent, supratentorial ependymoma developed extraneural metastases: one in a cervical lymph node, one with a scalp nodule, and one with a dural lesion. Each extraneural recurrence had similar histologic and molecular features as the initial diagnosis. The cervical lymph node recurrence was treated with multimodal therapy; she is without disease four years later. The isolated scalp nodule occurred at the exit site of a subgaleal drain placed during prior resection. Following nodule resection, he developed additional scalp and lymph node disease and is receiving palliative care. The isolated dural recurrence occurred at the exit site of a ventriculoperitoneal shunt placed following a previous resection. She died of progressive disease 18 months after dural lesion resection. Reports of lymph node, scalp, and dural metastases of ependymomas are exceedingly rare, and outcomes are poor. CONCLUSIONS Extraneural manifestations of ependymoma are rare. Regional seeding from prior surgical procedures may play a role in metastatic spread. Extraneural metastases should be considered in children previously treated for ependymoma who develop local findings even in the absence of CNS relapse. Salvage therapy with curative intent should be considered using a multimodal approach.
Inhibitory effect of PPARγ on NLRP3 inflammasome activation
Authors: Ching-Chun Yang, Chih-Hsing Wu, Ta-Chun Lin, Yi-Ning Cheng, Chin-Sung Chang, Kuo-Ting Lee, Pei-Jane Tsai, Yau-Sheng Tsai
Journal: Theranostics (2020)

Rationale: Stimulation of the NLRP3 inflammasome by metabolic byproducts is known to result in inflammatory responses and metabolic diseases. However, how the host controls aberrant NLRP3 inflammasome activation remains unclear. PPARγ, a known regulator of energy metabolism, plays an anti-inflammatory role through the inhibition of NF-κB activation and additionally attenuates NLRP3-dependent IL-1β and IL-18 production. Therefore, we hypothesized that PPARγ serves as an endogenous modulator that attenuates NLRP3 inflammasome activation in macrophages. Methods: Mouse peritoneal macrophages with exposure to a PPARγ agonist at different stages and the NLRP3 inflammasome-reconstituted system in HEK293T cells were used to investigate the additional anti-inflammatory effect of PPARγ on NLRP3 inflammasome regulation. Circulating mononuclear cells of obese patients with weight-loss surgery were used to identify the in vivo correlation between PPARγ and the NLRP3 inflammasome. Results: Exposure to the PPARγ agonist, rosiglitazone, during the second signal of NLRP3 inflammasome activation attenuated caspase-1 and IL-1β maturation. Moreover, PPARγ interfered with NLRP3 inflammasome formation by decreasing NLRP3-ASC and NLRP3-NLRP3 interactions as well as NLRP3-dependent ASC oligomerization, which is mediated through interaction between the PPARγ DNA-binding domain and the nucleotide-binding and leucine-rich repeat domains of NLRP3. Furthermore, PPARγ was required to limit metabolic damage-associated molecular pattern-induced NLRP3 inflammasome activation in mouse macrophages. Finally, the mature caspase-1/PPARγ ratio was reduced in circulating mononuclear cells of obese patients after weight-loss surgery, which we define as an "NLRP3 accelerating index". Conclusions: These results revealed an additional anti-inflammatory role for PPARγ in suppressing NLRP3 inflammasome activation through interaction with NLRP3. Thus, our study highlights that PPARγ agonism may be a therapeutic option for targeting NLRP3-related metabolic diseases.
BIOM-47. LONGITUDINAL MONITORING OF PLASMA H3K27M IN DIFFUSE MIDLINE GLIOMA PATIENTS TREATED WITH ONC201
Authors: Rohinton S Tarapore, Amanda Field, D Ashley Hill, Joshua Allen
Journal: Neuro-Oncology (2020)

Abstract Diffuse midline glioma, H3 K27M-mutant (DMG) is a 2016 WHO Grade IV glioma that has no established treatment beyond first-line radiation. ONC201 is an investigational small molecule that has been shown to be clinically active in recurrent DMG clinical trials. While biopsies of DMG are sometimes feasible, many patients defer secondary to complication risk. MR scans have many limitations in monitoring DMG progression, including distinguishing pseudoprogression and pseudoresponse and measuring diffuse lesions that often do not contrast enhance. Digital droplet PCR (ddPCR) is capable of sensitively detecting and quantifying the allelic frequency of circulating-tumor DNA (ctDNA) fragments against a backdrop of non-tumor DNA. Using sequence-specific probes for H3F3A (H3.3 K27M) and HIST1H3B (H3.1 K27M) ddPCR detects very low frequency variants and provides an assessment of mutational burden. A pilot cohort of 5 patients treated with ONC201 who had a range of outcomes were assessed with serial ctDNA analyses. Two patients with immediately progressive disease had a concordant H3 K27M ctDNA increase that precedes radiographic detection by 4 weeks. Two patients with &amp;gt;50% tumor regressions while on ONC201 had concordant H3 K27M ctDNA burden at the onset of response and subsequent radiographic progression was preceded by increases in ctDNA 8–16 weeks prior. One patient who had prolonged stable disease had decreased H3 K27M ctDNA burden over time. Upon radiographic progression, the addition of bevacizumab with ONC201 caused a radiographic pseudoresponse, however H3 K27M ctDNA remained stable. These pilot results suggest H3 K27M ctDNA may be a sensitive and accurate biomarker of disease burden. Longitudinal evaluation of H3 K27M ctDNA in a cohort of 34 recurrent contrast-enhancing H3 K27M-mutant glioma patients while on ONC201 will be reported. Primary tumor locations range across the thalamus, cerebellum, basal ganglia, temporal lobe, and midbrain; median age is 31 years old (range 20–70).
EPCO-15. TUMOR TREATMENT WITH IONIZING RADIATION IS ASSOCIATED WITH A CLINICALLY RELEVANT DELETION SIGNATURE
Authors: Emre Kocakavuk, Kevin Anderson, Kevin Johnson, Frederick Varn, Samirkumar Amin, Floris Barthel, Roel Verhaak
Journal: Neuro-Oncology (2020)

Abstract Diffuse gliomas are highly aggressive brain tumors that invariably relapse despite treatment with chemo- and radiotherapy. Treatment with alkylating chemotherapy can drive tumors to develop a hypermutator phenotype. In contrast, the genomic effects of radiation therapy (RT) remain unknown. We analyzed the mutational spectra following treatment with ionizing radiation in sequencing data from 190 paired primary-recurrent gliomas from the Glioma Longitudinal Analysis (GLASS) dataset and 2249 post-treatment metastatic tumors from the Hartwig Medical Foundation. We identified a significant increase in the frequency of small deletions following radiation therapy that was independent of other factors. These novel deletions demonstrated distinct characteristics when compared to pre-existing deletions present prior to RT-treatment and deletions in RT-untreated tumors. Radiation therapy-acquired deletions were characterized by a larger deletion size (GLASS and metastatic cohort, P = 1.2e-02 and P = 8e-11, respectively; Mann-Whitney U test), an increased distance to repetitive DNA elements (P &amp;lt; 2.2e-16, Kolmogorov-Smirnov test) and a reduction in microhomology at breakpoints (P = 3.2e-02, paired Wilcoxon signed-rank test). These observations suggested that canonical non-homologous end joining (c-NHEJ) was the preferred pathway for DNA double strand break repair of RT-induced DNA damage. Furthermore, radiotherapy resulted in frequent chromosomal deletions and significantly increased frequencies of CDKN2A homozygous deletions. Finally, a high burden of RT-associated deletions was associated with worse clinical outcomes (GLASS and metastatic cohort, P = 4.7e-02, HR = 2.59 [95% CI: 1.01, 6.60] and P = 2.5e-02, HR = 1.43 [95% CI: 1.05, 1.94], respectively; multivariable Cox regression), suggesting that effective repair of RT-induced DNA damage is detrimental to patient survival and that inhibiting c-NHEJ may be a viable strategy for improving the cancer-killing effect of radiotherapy. Taken together, the identified genomic scars as a result of radiation therapy reflect a more aggressive tumor with increased levels of resistance to follow up treatments.
71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results
Authors: D.P. Zandberg, R. Ferris, D. Laux, R. Mehra, L. Nabell, J. Kaczmar, M.K. Gibson, Y.J. Kim, P. Neupane, J. Bauman, R. Julian, D. Adkins, E. Cohen, B. Burtness, C. Bermingham, A. Dupage, A. Desbien, A. Loi, D.S.A. Nuyten, N.F. Saba
Journal: Annals of Oncology (2020)