tbuckley/cabot-search huggingface dataset:
Semi-supervised task-driven data augmentation for medical image segmentation
Authors: Krishna Chaitanya, Neerav Karani, Christian F. Baumgartner, Ertunc Erdil, Anton Becker, Olivio Donati, Ender Konukoglu
Journal: Medical Image Analysis (2020)

Supervised learning-based segmentation methods typically require a large number of annotated training data to generalize well at test time. In medical applications, curating such datasets is not a favourable option because acquiring a large number of annotated samples from experts is time-consuming and expensive. Consequently, numerous methods have been proposed in the literature for learning with limited annotated examples. Unfortunately, the proposed approaches in the literature have not yet yielded significant gains over random data augmentation for image segmentation, where random augmentations themselves do not yield high accuracy. In this work, we propose a novel task-driven data augmentation method for learning with limited labeled data where the synthetic data generator, is optimized for the segmentation task. The generator of the proposed method models intensity and shape variations using two sets of transformations, as additive intensity transformations and deformation fields. Both transformations are optimized using labeled as well as unlabeled examples in a semi-supervised framework. Our experiments on three medical datasets, namely cardiac, prostate and pancreas, show that the proposed approach significantly outperforms standard augmentation and semi-supervised approaches for image segmentation in the limited annotation setting. The code is made publicly available at https://github.com/krishnabits001/task_driven_data_augmentation.
Trial of Dexamethasone for Chronic Subdural Hematoma
Authors: Peter J. Hutchinson, Ellie Edlmann, Diederik Bulters, Ardalan Zolnourian, Patrick Holton, Nigel Suttner, Kevin Agyemang, Simon Thomson, Ian A. Anderson, Yahia Z. Al-Tamimi, Duncan Henderson, Peter C. Whitfield, Monica Gherle, Paul M. Brennan, Annabel Allison, Eric P. Thelin, Silvia Tarantino, Beatrice Pantaleo, Karen Caldwell, Carol Davis-Wilkie, Harry Mee, Elizabeth A. Warburton, Garry Barton, Aswin Chari, Hani J. Marcus, Andrew T. King, Antonio Belli, Phyo K. Myint, Ian Wilkinson, Thomas Santarius, Carole Turner, Simon Bond, Angelos G. Kolias
Journal: New England Journal of Medicine (2020)

Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied.
リポ蛋白(a)[Lp(a)]の高リポ蛋白質血症を合併する患者は抗メタボリック症候群の臨床的背景にもかかわらず重篤な冠動脈病変を持つ
Authors: Kasahara Takashi, Endoh Satoshi, Kinugasa Yoshiharu, Osaki Shuichi, Ohtahara Akira
Journal: Circulation (2007)
LINC-02. IMPLEMENTATION OF AN INTEGRATED NEURO-ONCOLOGY SERVICE: CLINICIANS’ PERSPECTIVE ON CONDUCT OF NEURO-ONCOLOGY MULTIDISCIPLINARY TEAM MEETING FROM A SINGLE-INSTITUTION IN MALAYSIA
Authors: Jen Chun Foo, Jawin Vida, Ariffin Hany, Pei Yuin Loh, Sockalingam Sutharsan, Ganesan Dharmendra, Thambinayagam Hari Chandran, Rajagopal Revathi
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Multidisciplinary Team (MDT) meetings are essential in the management of complex cancer cases. There are limited data regarding clinicians’ perception on conduct of neuro-oncology MDT meetings and its impact on clinical management. In University Malaya Medical Centre (UMMC), weekly neuro-oncology MDT meeting was established since 2013 to discuss adult and paediatric complex central nervous system tumour cases. OBJECTIVE To determine clinicians’ perception and level of satisfaction of neuro-oncology MDT meeting. METHODOLOGY Web-based questionnaire was distributed via e-mail to all neuro-oncology MDT clinicians at UMMC in April 2019. RESULT Eighteen out of 20 clinicians responded to the survey. Respondents were: neurosurgeons (n=5), adult oncologists (n=4), paediatric oncologists (n=3), radiologists (n=2), radiation oncologists (n=2) and pathologists (n=2). Majority of clinicians (65%) agreed at current weekly MDT meeting with maximum length of one hour duration and 75% of them suggested to discuss 5 to 10 cases during each meeting. Almost all of them (94.4%) preferred e-mail as method of communication to disseminate information before and after the meetings. MDT members expected 100% attendance from neurosurgeons. Fourteen (70%) clinicians agreed that patients/ parents/ carers do not receive copy of MDT meeting plans and only seven (35%) clinicians document MDT meeting plans in patients’ medical record. Overall, all clinicians felt that MDT meeting improved decision-making process, enhanced continuity of coordinated care and promoted good communication among team members. CONCLUSION The structure and logistics of neuro-oncology MDT meeting in UMMC are generally agreed upon. However, documentation of post-meeting plan and notification to patients need uniformity.
ATRT-30. RETROSPECTIVE ANALYSIS OF CHILDREN WITH ATYPICAL TERATOID RHABDOID TUMOR TREATED ACCORDING TO ACNS0333
Authors: Lindsey Hoffman, Ashley Margol, Kelly Faulk, Sara Hutchins, Gregory Friedman, Alyssa Reddy, Girish Dhall
Journal: Neuro-Oncology (2020)

Abstract Atypical teratoid rhabdoid tumor (ATRT) is a central nervous system tumor with poor outcome. ACNS0333, a Children’s Oncology Group phase 3 trial, enrolled 65 evaluable patients who received two cycles of induction chemotherapy, three cycles of consolidative high-dose chemotherapy (HDCT), and focal radiation therapy (RT) pre- or post-consolidation. Craniospinal irradiation (CSI) was left to clinician discretion. We retrospectively analyzed medical records of 27 children treated at our institutions according to ACNS0333. Median age at diagnosis was 14 months (range 4–165); 13 (48%) were male. M-stage was M0, M2, and M3 for 18 (66%), 5 (19%), and 4 (15%), respectively. Tumor location was supratentorial (n=14, 52%), infratentorial (n=12, 44%), or both (n=1, 4%). Complete resection was achieved for 17 (63%). All but one completed induction. Of 13 (51%) with residual disease at diagnosis, 5 (36%) and 7 (50%), respectively, exhibited complete and partial response to induction. Three patients progressed on therapy, and six progressed after completion of therapy at a median of 9.7 months. In all, 18 patients completed RT (16 focal/4 CSI and 6 pre-/12 post-consolidation). Three died of therapy-related toxicity (two in primary therapy and one in relapse therapy), and 8 died of disease. Sixteen patients (59%) are alive at a median follow up of 53 months (range 9–114). Of 17 with germline testing, eight (47%) had rhabdoid predisposition syndrome of whom three are alive. At the time of presentation, data for approximately 50 patients is expected, and we will compare outcomes to soon-to-be published data from ACNS0333.
Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study
Authors: Niloufer Khan, Sarah Lindner, Antonio L. C. Gomes, Sean M. Devlin, Gunjan L. Shah, Anthony D. Sung, Craig S. Sauter, Heather J. Landau, Parastoo B. Dahi, Miguel-Angel Perales, David J. Chung, Alexander M. Lesokhin, Anqi Dai, Annelie Clurman, John B. Slingerland, Ann E. Slingerland, Daniel G. Brereton, Paul A. Giardina, Molly Maloy, Gabriel K. Armijo, Carlos Rondon-Clavo, Emily Fontana, Lauren Bohannon, Sendhilnathan Ramalingam, Amy T. Bush, Meagan V. Lew, Julia A. Messina, Eric Littmann, Ying Taur, Robert R. Jenq, Nelson J. Chao, Sergio Giralt, Kate A. Markey, Eric G. Pamer, Marcel R. M. van den Brink, Jonathan U. Peled
Journal: Blood (2020)
STEM-14. GLIOBLASTOMA STEM CELL TARGETING CHIMERIC ANTIGEN RECEPTOR T CELLS MODIFIED USING PHAGE DISPLAY ISOLATED PEPTIDES
Authors: Marine Potez, Sebastian Snedal, Jongmyung Kim, Konrad Thorner, Maria Cecilia Ramello, Daniel Abate-Daga, James Liu
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with high mortality rates and resistance to conventional therapy. Their resistance to conventional therapy has been attributed to the presence of cancer stem cells (CSCs), a sub-population of tumor cells capable of self-renewal and tumor initiation. Developing novel strategies to specifically target GSCs may allow more effective therapeutic strategies. Using in vivo phage display biopanning, we have identified several peptides with the potential to selectively target and bind GSCs. We wished to leverage the GSC targeting properties of the peptides to augment therapeutic delivery vehicles for the development of novel targeting strategies. We used a combination of GSC targeting peptides to modify the antigen-binding domain of chimeric antigen receptors, by arranging the peptides in tandem at the N-terminus of the CAR molecule. These tandem peptides were tested for binding to GSCs in vitro and in vivo. The functionality of the CAR-T cells was evaluated by measuring cytokine release in the supernatant after overnight co-culture through ELISA. Apoptosis was evaluated by flow cytometry with Annexin V staining. Two different GSC-targeting peptide CAR-T cells demonstrated specific targeting GSCs. Following co-culture with GSCs, GSC targeting CAR-T cells were activated with release of Interferon gamma and subsequently induced GSCs specific apoptosis. These results demonstrate the use of phage display biopanning to isolate GSC targeting peptides which may be used to develop novel GBM specific cytotoxic therapies.
MBCL-15. IMPACT OF MOLECULAR SUBGROUPS ON OUTCOMES FOLLOWING RADIATION TREATMENT RANDOMIZATIONS FOR AVERAGE RISK MEDULLOBLASTOMA: A PLANNED ANALYSIS OF CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331
Authors: Jeff Michalski, Paul Northcott, Yimei Li, Catherine Billups, Kyle Smith, Peter Burger, Thomas Merchant, Amar Gajjar, T J Fitzgerald, Gilbert Vezina, Maryam Fouladi, Roger Packer, Nancy Tarbell, Anna Janss
Journal: Neuro-Oncology (2020)

Abstract The COG conducted a randomized trial for average-risk medulloblastoma (AR-MB). Patients age 3–21 years were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT) after receiving CSI. Patients age 3–7 years were also randomized to standard dose CSI (23.4Gy, SDCSI) or low dose CSI (18Gy, LDCSI). 464 evaluable patients were available to compare PFRT vs. IFRT and 226 for SDCSI vs. LDCSI. 380 cases had sufficient tissue for DNA methylation-based molecular classification: 362 confirmed medulloblastoma; 6 non-medulloblastoma; 12 inconclusive. Molecular subgrouping confirmed the following representation amongst the evaluable cohort: 156 Group 4 (43.1%), 76 Group 3 (21.0%), 66 SHH (18.2%), 64 WNT (17.7%). Five-year event-free survival (EFS) estimates were 82.5±2.7% and 80.5±2.7% for IFRT and PFRT, respectively (p=0.44). Five-year EFS estimates were 71.4±4.4% and 82.9±3.7% for LDCSI and SDCSI, respectively (p=0.028). EFS distributions differed significantly by subgroup (p&amp;lt;0.0001). Group 3 had the worst outcome, while WNT had the best outcome. There was a significant difference in EFS by RT group among SHH patients; SHH patients receiving IFRT arm had better EFS compared to PFRT (p=0.018). There was a significant difference in EFS distributions by CSI group in Group 4 patients; young Group 4 patients treated with SDCSI had better EFS compared to LDCSI (p=0.047). As previously reported, IFRT is noninferior to PFRT in all patients with AR-MB but LDCSI is worse than SDCSI in younger children. Significant differences in outcome by study randomization and molecular subgroup are observed.
RARE-33. GIANT CELL TUMOR OF THE SKULL BASE WITH A HISTORY OF A SUCCESSFUL RESPONSE TO DENOSUMAB AND LATER DEVELOPING A SECOND TUMOR
Authors: Manushak Avagyan, Gevorg Tamamyan, Samvel Danielyan, Martin Harutyunyan, Nune Karapetyan, Nerses Karamyan, Hovhannes Vardevanyan, Armen Mkhitaryan, Samvel Bardakhchyan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Giant cell tumor of bone(GCTB) is a rare neoplasm with unpredictable behavior, possible malignant transformations, and/or lung metastases. Surgery is usually the treatment of choice. In unresectable or metastatic cases, treatment with denosumab is a new treatment option. CASE PRESENTATION: A 14-years-old female presented with cachexia, dysphagia, diplopia, discoordination, strabismus, and multiple cranial nerve palsies in 10.2015. MRI revealed intra-extracranial mass arising from C2 vertebrae, compressing the medulla oblongata and the left cerebellar hemisphere, invading to the sphenoid bone and nasopharynges. Biopsy showed a GCTB. Surgical resection was done, which was incomplete because of tumor location (cranial nerve and vertebral artery involvement). Then local radiation therapy was performed 50.4Gy. During RT patient’s condition declined and MRI showed disease progression. Treatment with denosumab 120mg q4w was initiated in 03.2016, which yielded successful results. Disease was under control for three years until 03.2019. Then she returned with clinical symptoms of diplopia and severe headache. MRI showed local tumor progression. Repeated biopsy revealed undifferentiated pleomorphic sarcoma, which could be either a malignant transformation of GCTB or a new tumor. The patient later underwent two cycles of chemotherapy with Ifosfamide/Doxorubicin. MRI after 2nd cycle showed marked tumor progression. The patient didn’t receive any further treatment because of cachexia and died due to disease progression in 12.2019. CONCLUSION To our knowledge, this is the youngest patient ever reported with a skull base tumor with such a clinical development, successful and long-time remission with denosumab and with such a chemotherapy-resistant malignant transformation or second cancer.
Accuracy and Reproducibility of Intraoperative Assessment on Tumor Spread Through Air Spaces in Stage 1 Lung Adenocarcinomas
Authors: Julian A. Villalba, Angela R. Shih, Treah May S. Sayo, Keiko Kunitoki, Yin P. Hung, Amy Ly, Marina Kem, Lida P. Hariri, Ashok Muniappan, Henning A. Gaissert, Yolonda L. Colson, Michael D. Lanuti, Mari Mino-Kenudson
Journal: Journal of Thoracic Oncology (2020)
Assessment of Plasma Amyloid-β<sub>42/40</sub>and Cognitive Decline Among Community-Dwelling Older Adults
Authors: Kelly Virecoulon Giudici, Philipe de Souto Barreto, Sophie Guyonnet, Yan Li, Randall John Bateman, Bruno Vellas
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. <h3>Objective</h3> To investigate the associations between plasma Aβ<sub>42/40</sub>and cognitive decline over time among community-dwelling older adults with subjective memory concerns. <h3>Design, Setting, and Participants</h3> This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. <h3>Exposure</h3> Plasma Aβ<sub>42</sub>and Aβ<sub>40</sub>were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aβ assessment was defined as the baseline for this study. <h3>Main Outcomes and Measures</h3> Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study–Activities of Daily Living. Mixed-effect linear regressions were performed. <h3>Results</h3> A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aβ<sub>42/40</sub>(≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aβ<sub>42/40</sub>was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: −0.20, 95% CI, −0.34 to −0.07;<i>P</i> = .004) and decline in MMSE score (adjusted between-group mean difference: −0.59; 95% CI, −1.07 to −0.11;<i>P</i> = .02) during the follow-up period compared with the group with an Aβ<sub>42/40</sub>ratio greater than 0.107. <h3>Conclusions and Relevance</h3> In this study, low plasma Aβ<sub>42/40</sub>was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aβ<sub>42/40</sub>may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.
DIPG-35. BIOLOGICAL MEDICINE FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) ERADICATION: RESULTS OF THE THREE ARM BIOMARKER-DRIVEN RANDOMIZED BIOMEDE 1.0 TRIAL
Authors: Jacques Grill, Gwenael Le Teuff, Karsten Nysom, Klas Blomgren, Darren Hargrave, Geoff MacCowage, Francisco Bautista, Dannis Van Vuurden, Volodia Dangouloff-Ros, Stephanie Puget, Pascale Varlet, Marie-Anne Debily, Gilles Vassal, Marie-Cecile Le Deley
Journal: Neuro-Oncology (2020)

Abstract Despite 50 years of clinical trials, no improvement of survival has been observed in DIPG and most children die within 2 years of diagnosis. Only radiotherapy transiently controls disease progression. The study was conceived as a randomized multi-arm multi-stage program. It started with an open-label phase-II trial comparing three drugs (everolimus, dasatinib, erlotinib) combined with irradiation, allocated according to the presence of their specific targets (PTEN-loss, EGFR-overexpression) defined with a stereotactic biopsy after central confirmation of the diagnosis (presence of histone H3K27M mutation or loss of K27 trimethylation). Targeted therapies were started concomitantly with radiotherapy and were continued until disease progression. No biopsy-related death was reported and diagnostic yield was excellent, with only 5 non-informative biopsies. Biopsy excluded the diagnosisof DIPG in 8% of the cases. At the 3rd interim analysis, based on 193 randomized patients, the IDMC concluded that the study was unlikely to show a difference of OS between the 3 drugs even if 250 patients would be randomized. The median OS from the time of diagnosis was 11.9, 10.5 and 10 months for everolimus, dasatinib and erlotinib. Treatment was discontinued due to toxicity in 2%, 13%, and 15%, respectively. BIOMEDE shows the feasibility of biologically-driven treatment in DIPG on a large international scale. Based on the better toxicity profile and the slightly better efficacy, although not statistically significant, the steering committee proposed that everolimus should be used as the control arm for the next BIOMEDE 2.0 trial.
Abstract 14675: Anatomical Determinants of Wave Reflection in Repaired Coarctation of the Aorta
Authors: Michael A Quail, Vivek Muthurangu
Journal: Circulation (2017)

Introduction: Wave reflections have recently been shown to be the major determinant of LV remodeling in adults following coarctation of the aorta (CoA) repair. However the relationship between the ...
CTNI-17. CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA
Authors: Abed Rahman Kawakibi, Rohinton S Tarapore, Sharon Gardner, Chase Thomas, Rodrigo Cartaxo, Viveka Nand Yadav, Andrew Chi, Sylvia Kurz, Patrick Wen, Isabel Arrillaga-Romany, Tracy Batchelor, Nicholas Butowski, Ashley Sumrall, Nicole Shonka, Rebecca Harrison, John de Groot, Minesh Mehta, Yazmin Odia, Matthew Hall, Doured Daghistani, Timothy Cloughesy, Benjamin Ellingson, Yoshie Umemura, Hugh Garton, Andrea Franson, Patricia Robertson, Jonathan Schwartz, Evan Cantor, Zachary Miklja, Brendan Mullan, Amy Bruzek, Ruby Siada, Jessica Cummings, Alyssa Paul, Ian Wolfe, Li Jiang, Mariella Filbin, Pankaj Vats, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Sriram Venneti, Guangrong Lu, Sabine Mueller, Daniel Martinez, Adam Resnick, Javad Nazarian, Sebastian Waszak, Joshua Allen, Carl Koschmann
Journal: Neuro-Oncology (2020)

Abstract Patients with diffuse midline glioma (DMG) harboring H3 K27M mutation rarely survive longer than two years and have no proven therapies following first-line radiation. ONC201, a bitopic DRD2 antagonist and allosteric ClpP agonist, has shown encouraging efficacy in early phase studies in H3 K27M-mutant DMG. In order to define response rates in H3 K27M DMG patients and to clarify the genomic, anatomic and molecular predictors of response, we performed an integrated pre-clinical and clinical analysis of ONC201 treatment. ONC201 was effective in intra-uterine electroporation (IUE)-generated H3 K27M-mutant murine glioma models with excellent CNS penetration and survival benefit. Patients with H3 K27M-mutant DMG treated with ONC201 on active clinical trials (n=50, 27 thalamic, 23 brainstem) showed an overall survival (OS) of 28.1 (range: 5.9–105) months from diagnosis (enrollment by 4/29/19, data cut-off 12/28/19), compared to historical median OS of 12 months. Median OS for non-recurrent patients has not been reached (n=16, median follow-up: 16.8 from diagnosis). For non-recurrent thalamic patients (n=8), median PFS is 20.1 (range: 9.3–27.6) months from diagnosis (median time on drug: 14.5 months). Best response for thalamic patients by RANO: 1 CR, 5 PR, 7 SD, 8 PD, 6 not reported. Decreased H3 K27M cell-free tumor DNA in plasma and CSF at 6 months correlated with long-term response. Baseline tumor gene expression profiling in patients treated with ONC201 (n=14) identified EGFR and the cortical developmental transcription factor FOXG1 as the strongest biomarkers of radiographic response to ONC201. Analysis of 541 ONC201-treated human cancer cell lines from DepMap, provided evidence for an EGFR-dependent ONC201 resistance mechanism. Analysis of 38 glioma cell lines further supports FOXG1 as a glioma-specific predictive biomarker of ONC201 response. The unprecedented survival results and radiographic responses to ONC201 in H3K27M DMG make a compelling case for later phase and combinatorial studies.
STARRPeaker: uniform processing and accurate identification of STARR-seq active regions
Authors: Donghoon Lee, Manman Shi, Jennifer Moran, Martha Wall, Jing Zhang, Jason Liu, Dominic Fitzgerald, Yasuhiro Kyono, Lijia Ma, Kevin P. White, Mark Gerstein
Journal: Genome biology (2020)

Abstract STARR-seq technology has employed progressively more complex genomic libraries and increased sequencing depths. An issue with the increased complexity and depth is that the coverage in STARR-seq experiments is non-uniform, overdispersed, and often confounded by sequencing biases, such as GC content. Furthermore, STARR-seq readout is confounded by RNA secondary structure and thermodynamic stability. To address these potential confounders, we developed a negative binomial regression framework for uniformly processing STARR-seq data, called STARRPeaker. Moreover, to aid our effort, we generated whole-genome STARR-seq data from the HepG2 and K562 human cell lines and applied STARRPeaker to comprehensively and unbiasedly call enhancers in them.