tbuckley/cabot-search huggingface dataset:
Abstract P381: Diabetes Prevention Program Football Club: A 6-month Intervention Among Latino Men
Authors: Jennifer K Frediani, Jianheng Li, Felipe Lobelo
Journal: Circulation (2020)

Purpose: One third of the U.S. adult population is estimated to have prediabetes. Hispanics have a 50% higher type 2 diabetes (T2DM) death rate compared to non-Hispanic whites, yet low participation in lifestyle change programs, making this subgroup an important target for prevention efforts. The purpose of this study was to determine the effects of an intervention implementing the Center for Disease Control and Prevention (CDC) National Diabetes Prevention Program (NDPP) plus recreational soccer (RS) in Hispanic men. Methods: Overweight and obese Hispanic men, aged 30-57 years with prediabetes at screening were recruited from the community. Enrolled participants were divided into three cohorts. Trained soccer coaches led 30-minute facilitated discussion of the NDPP modules after each RS session, with two sessions per week for 3 months and once per week for the following 3 months. The 1-hour RS sessions followed the Football Fitness curriculum structure. Standardized study assessments included body mass index, waist circumference, multi-frequency bioelectrical impedance analysis (InBody 270), blood pressure, hemoglobin A1c, and validated field physical fitness tests (figure of 8 run, handgrip strength, vertical jump, modified sit-ups, dynamic push-ups, one leg stand and Yo-Yo intermittent sprint test). Mixed models assessed the outcomes as a function of time and cohort and incorporated an unstructured covariance structure to examine the difference between baseline and 6 months. All analyses were conducted as intent-to-treat and generated using SAS v 9.4. Results: Hispanic males (n=41; mean age 41.7 [0.1] years) were obese at baseline (mean BMI 32.7, standard error [0.7], mean weight 93.9 [2.2] kg). After 6 months of the NDPP+RS intervention, there were significant changes in systolic and diastolic blood pressure (-6.6 [2.4]; p=0.01 and -6.1 [1.7] mmHg; p&lt;0.001, respectively), HbA1c -0.2 [0.1]; p=0.005, figure of 8-agility run (-0.5 [0.1] sec; p&lt;0.0001), number of modified push-ups in 40 seconds (3.9 [0.6]; p&lt;0.0001), dynamic sit-ups (1.9 [0.4]; p&lt;0.0001), and predicted VO 2 (ml/kg/min) (0.4 [0.2]; p=0.04. Despite significant reductions in weight (-3.8 kg [0.7]; p&lt;0.0001), waist circumference (-6.6 [0.7] cm; p&lt;0.0001), body fat % (-1.9 kg [0.5]; p=0.0002), lean body mass was mostly preserved [-0.9 [0.3]; p=0.009]. Conclusion: Among middle-aged Latino men, broad-ranging significant improvements in body composition, physical fitness, HbA1c and blood pressure were observed after 6 months of participating in lifestyle education plus RS.
SURG-21. A CROWDSOURCED CONSENSUS ON SUPRATOTAL RESECTION VERSUS GROSS TOTAL RESECTION FOR ANATOMICALLY DISTINCT PRIMARY GLIOBLASTOMA
Authors: Debraj Mukherjee, Maureen Rakovec, Chetan Bettegowda, Christopher Jackson, Gary Gallia, Michael Lim, Jon Weingart, Yoshua Esquenazi, Brad Zacharia, Ezequiel Goldschmidt, Mateo Ziu, Michael Ivan, Andrew Venteicher, Edjah Nduom, Adam Mamelak, Ray Chu, John Yu, Jason Sheehan, Brian Nahed, Bob Carter, Mitchel Berger, Raymond Sawaya, Adham Khalafallah
Journal: Neuro-Oncology (2020)

Abstract Gross total resection (GTR) of contrast-enhancing tumor is associated with significantly increased overall survival in primary glioblastoma (GBM). Even when achieved, recurrence is likely, in part due to malignant cells infiltrating outside enhanced regions. Subsequently, there has been increasing interest in performing supratotal resections (SpTRs) for GBM. Published results have varied in part due to a lack of consensus on the definition of SpTR in GBM and its appropriate use. A crowdsourcing approach was used to survey 21 academic neurosurgical oncologists representing 13 health systems nationwide. Participants’ demographics including fellowship training status, years of experience, and operative volume with various techniques was collected. Participants were presented with 11 definitions of SpTR from published, peer-reviewed studies and asked to rate the appropriateness of each definition. Subsequently, participants reviewed T1-weighed post-contrast and FLAIR MR imaging videos in the axial, coronal, and sagittal planes for 22 GBMs. Participants were asked to assess eloquence of the tumor’s location, perceived equipoise of enrolling patients in a randomized clinical trial comparing GTR to SpTR, and their own personal surgical treatment plans. Most neurosurgeons surveyed (n=18, 85.7%) agree or strongly agree that GTR plus resection of some non-contrast enhancement is an appropriate definition for SpTR. Overall, there was only moderate inter-rater agreement, measured using sample variance and the index of qualitative variation, regarding eloquence, equipoise, and personal treatment plans. Neurosurgeons who performed more than 10 SpTRs for GBMs in the past year were more likely than counterparts to recommend it as their personal treatment plan (p&amp;lt; 0.005). Anterior temporal and right frontal GBMs were considered the best randomization candidates. We established a consensus definition for SpTR of GBM and identified anatomically distinct locations deemed most amenable to SpTR. These results will be used to plan prospective trials further investigating the potential clinical utility of SpTR for GBMs.
INNV-13. SYNERGISTIC EFFECT OF COLD ATMOSPHERIC PLASMA IN COMBINATION WITH TEMOZOLOMIDE TO TREAT GLIOBLASTOMA IN A NON-INVASIVE MOUSE XENOGRAFT MODEL
Authors: Manish Adhikari, Vikas Soni, Simonyan Hayk, Colin Young, Jonathan Sherman, Michael Keidar
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION A primary limitation in anti-cancer therapy is the resistance of cancer cells to chemotherapeutic drugs. However, combination therapy may be an effective approach for reducing drug derived toxicity and evading drug resistance, resulting in improved clinical treatment of cancer. Our prior work demonstrated effective treatment of glioblastoma (GBM) with cold atmospheric plasma (CAP) technology with minimal effect to normal cells. Consequently, CAP may serve as a strong candidate for combination therapy with the classical antineoplastic alkylating agent Temozolomide (TMZ) to treat GBM. OBJECTIVES To determine the in vivo co-efficacy of CAP and TMZ to “sensitize” GBM. METHODS An in vivo study was performed using the CAP jet device (He-gas) to determine the effect of combined CAP–TMZ treatment. U87MG-luc glioblastoma cells were implanted intracranially in athymic nude NU(NCr)-Foxn1nu/immunodeficient mice. He-CAP (or control He alone) was non-invasively applied over the skin for 60sec to developed tumors on the first day of the treatment followed with 6.5 mg/kg TMZ or vehicle control treatment for 5 days for two weeks (n=5/group). In vivo bioluminescence imaging was used to monitor tumor volume on the 6th, 9th and 13th treatment day. RESULTS In vivo bioluminescence imaging revealed a marked 8.0±3.2 fold increase in tumor volume in control animals (He-vehicle). Treatment with He-TMZ (6.7±2.5 fold) or CAP-vehicle (4.8±1.7 fold) in isolation had minimal effect in preventing tumor growth. However, combined CAP-TMZ co-treatment virtually prevented increases in tumor volume over 2 weeks (1.8±0.2 fold). CONCLUSIONS Collectively, these findings indicate an effective synergistic treatment method for GBM combining CAP with TMZ. Future investigations look to incorporate radiation into the treatment regimen as well as primary GBM cell models.
CTNI-74. PHASE 3 TRIDENT TRIAL: CONCOMITANT RADIATION THERAPY (RT) AND TEMOZOLOMIDE +/- TUMOR TREATING FIELDS (TTFIELDS) IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Wenyin Shi, Lawrence Kleinberg, Suriya A Jeyapalan, Samuel Goldlust, Seema Nagpal, Stephanie E Combs, David Roberge, Ryo Nishigawa, Rachel Grossman, Martin Glas
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for newly diagnosed glioblastoma (ndGBM). In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of ndGBM patients without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. METHODS TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 KHz) will be delivered &amp;gt;18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, and amenable for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS6M, PF12M, PFS2Y); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR&amp;lt; 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.
EPCO-04. GENOMIC AND EPIGENOMIC HALLMARKS OF SCHWANNOMATOSIS SCHWANNOMAS
Authors: Sheila Mansouri, Suganth Suppiah, Yasin Mamatjan, Irene Paganini, Jeff Liu, Shirin Karimi, Vikas Patil, Farshad Nassiri, Olivia Singh, Yogi Sundaravadanam, Prisni Rath, Robert Sestini, Francesca Gensini, Sameer Agnihotri, Jaishri Blakeley, Kimberly Ostrow, David Largaespada, Scott Plotkin, Anat Stemmer-Rachamimov, Marcela Maria Ferrer, Trevor Pugh, Kenneth Aldape, Laura Papi, Gelareh Zadeh
Journal: Neuro-Oncology (2020)

Abstract Schwannomatosis (SWNTS) is a genetic cancer predisposition syndrome that manifests as multiple and often, painful neuronal tumors called schwannomas (SWNs). Very little is known about the epigenomic and genomic alterations in SWNTS related SWNs (SWNTS-SWNs) other than germline mutations in SMARCB1 and LZTR1 plus somatic mutations in NF2 and loss of heterozygosity in chromosome 22q. Herein, we have comprehensively established the specific molecular signatures of SWNTS-SWNs. We found that tumor anatomic location was associated with pain and distinct DNA methylation and transcriptional signatures. DNA sequencing revealed several novel non-22q deletions, specifically in LZTR1-mutant cases. Whole-genome sequencing identified novel recurrent structural rearrangements. Further, chromosomal aberrations in SWNTS-SWNs were accompanied by increased transcription of mismatch repair genes. Our transcriptome analysis detected the SH3PXD2A-HTRA1 gene fusion in SWNTS-SWNs, more commonly in LZTR1-mutant tumors. In addition, we identified the specific genetic, epigenetic, and transcriptional hallmarks of painful SWNs that may be harnessed to develop new treatments for this debilitating syndrome.
Disrupting the norms: Reproduction, gender identity, gender dysphoria, and intersectionality
Authors: Trevor Kirczenow MacDonald, Michelle Walks, MaryLynne Biener, Alanna Kibbe
Journal: International Journal of Transgender Health (2020)

Background: In western cultures, pregnancy and birth have typically been viewed as inherently feminine activities. However, some transmasculine individuals desire and undergo pregnancy. Aims: Our study aimed to explore the experiences of transmasculine individuals with pregnancy and birth. Methods: We conducted 22 qualitative interviews and four follow-up interviews with transmasculine individuals who had experienced one or more pregnancies. Our analysis was guided by an intersectional approach, and was led by a transgender community member. Results: The interviews focused on stories about how the study participants built their families and navigated health care systems in the context of being pregnant transgender persons. As part of a larger study that considered the pregnancy, birth and infant feeding experiences of transmasculine individuals, this paper examines three themes that emerged from the narratives: experiences of gender dysphoria, addressing the gender binary, and intersectionality. Discussion: Experiences of gender dysphoria among transmasculine individuals during pregnancy and birth vary widely. Some trans individuals experience pregnancy as congruent with their masculine gender identity. However, participants reported that some health care providers' strong belief in the gender binary led to inappropriate and oppressive reproductive and perinatal health care.
Asthma self-management with regular support reduces health care use and improves QoL at 8 mo
Authors: Christopher J. Worsnop, Christine F. McDonald
Journal: Annals of Internal Medicine (2020)

Source Citation Hodkinson A, Bower P, Grigoroglou C, et al. Self-management interventions to reduce healthcare use and improve quality of life among patients with asthma: systematic review and network meta-analysis. BMJ. 2020;370:m2521. 32816816
RARE-40. CASE REPORT: LONG-TERM SURVIVOR OF A RARE, PEDIATRIC PRIMARY HISTIOCYTIC SARCOMA (HS) OF THE CENTRAL NERVOUS SYSTEM (CNS) FOLLOWING COMPLETE RESECTION, CHEMOTHERAPY AND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT)
Authors: Diana S Osorio, Rolla Abu-Arja, Mohamed S Abdel-Baki, Jeffrey R Leonard, Eric A Sribnick, Jonathan L Finlay, David W Ellison, Jennifer Picarsic, Samir Kahwash, Daniel R Boue’
Journal: Neuro-Oncology (2020)

Abstract We report an unusual case of a patient with primary CNS-HS a very rare neoplasm of histiocytic lineage with usually poor prognosis. An 8 year old boy presented with a one month history of headaches, nausea and vomiting. Physical examination revealed nystagmus and dysmetria. Brain MRI revealed a localized 2.4 cm posterior fossa (cerebellar) mass with restricted diffusion. The patient underwent a gross total resection of the mass. Initial post-operative lumbar puncture was positive for rare malignant cells. Pathology showed a focally necrotic neoplasm, composed of nests and cords of large relatively uniform cells with abundant eosinophilic cytoplasm, moderately pleomorphic nuclei and numerous mitotic figures, consistent with CNS-HS with juvenile xanthogranuloma phenotype, as supported by positive IHC expression of CD163, CD68, CD14, fascin, and Factor XIIIa, while negative for CD1a, Lymphoid and Myeloid markers, and BRAFv600e mutation. He was treated with two cycles of clofarabine and cytarabine and triple intrathecal (IT) chemotherapy. He developed generalized seizures and MRI showed demyelination consistent with IT methotrexate toxicity; MTX was then discontinued. He was then given two additional cycles of cladribine and weekly intrathecal therapy prior to consolidation with an Allo-HCT using a 10/10 HLA allelic-matched unrelated donor. His conditioning regimen included total body irradiation and cyclophosphamide. He did well post-transplant with peripheral blood chimerism at 1 year showing &amp;gt; 95% donor cells. He remains disease-free with an excellent quality of life since August 2016. We report one of the few known survivors of this unusual and highly malignant entity.
MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway
Authors: Junhong Guan, Changzheng Lu, Qihuang Jin, Huiming Lu, Xiang Chen, Lei Tian, Yanbin Zhang, Janice Ortega, Junqiu Zhang, Silvia Siteni, Mingyi Chen, Liya Gu, Jerry W. Shay, Anthony J. Davis, Zhijian J. Chen, Yang-Xin Fu, Guo-Min Li
Journal: Cancer Cell (2020)
LINC-26. ORAL VINORELBINE IN PROGRESSIVE UNRESECTABLE LOW-GRADE GLIOMA
Authors: Andréa M Cappellano, Milena R S Oliveira, Sergio Cavalheiro, Patricia Dastoli, Daniela B Almeida, Frederico A Silva, Maria Teresa S Alves, Nasjla S Silva
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The management of progressive unresectable low-grade glioma (PULGG) remains controversial. Some series suggests that chemotherapy may delay or even avoid radiotherapy and/or surgery in a group of patients. Within this context, we performed at IOP/GRAACC/UNIFESP an institutional protocol with IV vinorelbine, a semi-synthetic vinca alkaloid that showed activity against PULGG. The objective of this study was to evaluate the response as long as the tolerability of oral vinorelbine in PULGG. PATIENTS AND METHODS From April 2013 to Aug 2017, 17 patients with recurrent (n=5) and newly-diagnosed (n=12) optic-pathway glioma (OPG) were treated with oral vinorelbine in a dose of 90 mg/m² days 0, 8 and 22 for 18 cycles. Response criteria used a combination of magnetic resonance imaging, physical and visual evaluation. RESULTS Mean age 8.6 years (4.8–17.9y). Three children with neurofibromatosis type 1. Eleven patients had neurosurgical intervention revealing grade I (n=8) and grade II astrocytoma (n=3). Twelve patients were assessable after 8 cycles of vinorelbine with 2 objective response (OR), 8 stable disease (SD) and 2 progressive disease (PD), one died after surgery and 1 alive in different protocol. After 18 cycles, eight patients were assessable to date for response with 1 OR, 7 SD. The most important toxicity was gastrointestinal observed in 12 patients- six of them switched to IV vinorelbine (3OR, 3SD). None of the patients showed neurotoxicity. CONCLUSION These results suggest that oral vinorelbine, as the IV formulation, may show some activity in OPG. However, gastrointestinal toxicity should be considered.
INNV-05. TUMOR TREATING FIELDS (TTFIELDS) TREATMENT PLANNING FOR A PATIENT WITH ASTROCYTOMA IN THE SPINAL CORD
Authors: Jennifer De Los Santos, Smadar Arvatz, Oshrit Zeevi, Shay levi, Zeev Bomzon, Tal Marciano
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The use of Tumor Treating Fields (TTFields) following resection and chemoradiation has increased survival in patients with Glioblastoma. Randomized data provide strong rationale for planning TTFields transducer array placement to maximize TTFields dose at the tumor in a patient-specific manner. Here we present a case demonstrating the use of numerical simulations for patient-specific TTFields treatment planning for a spinal tumor. METHODS Treatment planning was performed for a 48 year old patient following T10-L1 laminectomy, gross total resection, and postoperative chemoradiation for an anaplastic astrocytoma of the spinal cord. An MRI at 3 weeks following chemoradiation showed tumor recurrence. Based on the post-chemoradiation MRI, a patient-specific model was created. The model was created by modifying a realistic computational phantom of a healthy female. To mimic the laminectomy, the lamina in T10-L1 was removed, and the region assigned electric conductivity similar to that of muscle. A virtual mass was introduced into the spinal cord. Virtual transducer arrays were placed on the model at multiple positions, and delivery of TTFields simulated. The dose delivered by different transducer array layouts was calculated, and the layouts that yielded maximal dose to the tumor and spine identified. RESULTS Transducer array layouts, in which the arrays were placed on the back of the patient with one array above the tumor and one array below the tumor, yielded the highest doses at the tumor site. Such layouts yielded TTFields doses of over 3.4mW/cm3 which is well above the threshold dose of 1.1 mW/cm3 reported previously [Ballo et al Red Jour 2019]. CONCLUSIONS These data represent the first ever study on utilizing numerical simulations in order to plan treatment for a spinal tumor in a patient-specific manner. This is an important milestone in the developing a framework for TTFields dosimetry and treatment planning.
IMG-19. RADIOMICS AND SUPERVISED DEEP LEARNING TO PREDICT MOLECULAR SUBGROUPS IN MEDULLOBLASTOMA BASED ON WHOLE TUMOR VOLUME LABELING: A SINGLE CENTER MULTIPARAMETRIC MR ANALYSIS
Authors: Ioan Paul Voicu, Piero Chiacchiaretta, Massimo Caulo, Evelina Miele, Alessia Carboni, Andrea Carai, Francesca Diomedi-Camassei, Sabrina Rossi, Antonella Cacchione, Giada Del Baldo, Elisabetta Ferretti, Angela Mastronuzzi, Paolo Tomà, Giovanna Stefania Colafati
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Medulloblastoma (MB) is a complex pathology. Four molecular subgroups have been unveiled (Wingless-WNT, Sonic Hedgehog-SHH, Group 3-G3 and Group 4-G4), characterized by significant differences in patient clinical outcome. We investigated the utility of a radiomic analysis to predict molecular subgroups in patients with MB. MATERIALS AND METHODS We retrospectively evaluated 42 patients with histological diagnosis of MB, known molecular subgroup, and diagnostic MRI scan performed in our Institution on a 3 Tesla magnet. For each patient, FLAIR, ADC, T2 and contrast-enhanced MPRAGE sequences were analysed. Solid tumor volumes were segmented semiautomatically. 107 features were extracted for each sequence (Pyradiomics, Python). Features were tested for stability against labelling variations, selecting those presenting Intraclass Correlation Coefficient (ICC)&amp;gt;0.9 across all labelling variations and all sequences. Among the remaining features, relevant features were selected with an all-relevant wrapper algorithm (Boruta, R). Remaining features were used to predict MB subgroup with a Random Forest algorithm(R). The most relevant features were ranked based on Gini index (R). RESULTS 83/107 features presented ICC &amp;gt;0.9 for all sequences. Boruta selected 10 features. Classification analysis yielded an out-of-bag (OOB) error rate of 0.6%, (99.4% accuracy). The most relevant features for classification were “simple” first-order features such as volume, major axis or shape. CONCLUSION This radiomic study yielded robust features, which showed high accuracy in predicting the molecular MB subgroups. Random forest algorithms are ideal for multiclass classification (eg. MB subgroups) and are intrinsically suited against overfitting. The most relevant for molecular classification were first-order features.
Modulating hESC-derived cardiomyocyte and endothelial cell function with triple-helical peptides for heart tissue engineering
Authors: Maria Colzani, Jean-Daniel Malcor, Emma J. Hunter, Semih Bayraktar, Murray Polkinghorne, Thomas Krieg, Ruth Cameron, Serena Best, Richard W. Farndale, Sanjay Sinha
Journal: Biomaterials (2020)

In this study, we investigated the role of cardiomyocyte (CM) and endothelial cell (EC) specific interactions with collagen in the assembly of an operational myocardium in vitro. Engineered cardiac patches represent valuable tools for myocardial repair following infarction and are generally constituted of a suitable biomaterial populated by CMs and supportive cell types. Among those, ECs are required for tissue vascularization and positively modulate CM function. To direct the function of human embryonic stem cell (hESC)-derived CM and EC seeded on biomaterials, we replicated cell-collagen interactions, which regulate cellular behaviour in the native myocardium, using triple-helical peptides (THPs) that are ligands for collagen-binding proteins. THPs enhanced proliferation and activity of CMs and ECs separately and in co-culture, drove CM maturation and enabled coordinated cellular contraction on collagen films. These results highlight the importance of collagen interactions on cellular response and establish THP-functionalized biomaterials as novel tools to produce engineered cardiac tissues.