tbuckley/cabot-search huggingface dataset:
RBTT-05. A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY EVALUATING THE EFFICACY AND SAFETY OF ABEMACICLIB IN PATIENTS WITH RECURRENT OLIGODENDROGLIOMA: TRIALS IN PROGRESS
Authors: Stephen Bagley, MacLean Nasrallah, Donald O’Rourke, Jasmin Hussain, Eileen Maloney-Wilensky, Timothy Prior, Steven Brem, Arati Desai
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Oligodendroglioma is a rare primary brain tumor characterized by mutation in the IDH1/IDH2 genes and codeletion of chromosomes 1p and 19q. Although median overall survival extends beyond 10 years for patients with oligodendroglioma who receive adjuvant radiation and alkylating chemotherapy, the disease uniformly relapses and has no other effective treatments. The CIC gene, which encodes a high-mobility group box transcriptional repressor, is mutated in about 70% of oligodendrogliomas and is associated with worse prognosis and overexpression of cyclin D1 (CCND1). Cyclin D1 assembles with the cyclin-dependent kinases CDK4 and CDK6 to cause phosphorylation of Rb protein and subsequent cell cycle progression from the G1 to S phase. Therapeutic inhibition of CDK4/6 activity, which leads to Rb dephosphorylation and cell cycle arrest, has revolutionized the care of breast cancer. The current phase 2 study will investigate the efficacy and safety of abemaciclib, a selective and potent small molecule inhibitor of CDK4 and CDK6 with significant brain-brain barrier penetration, in patients with 1p/19q codeleted oligodendroglioma that has recurred after standard radiation and alkylating chemotherapy. METHODS This protocol (NCT03969706) has a single-arm, open-label, single-stage phase 2 design. Subjects will be treated with abemaciclib 200mg tablet twice daily on 28-day cycles until disease progression or unacceptable toxicity. Tumor response will be assessed according to modified Response Assessment in Neuro-Oncology (mRANO) criteria. The primary objective of the study is to determine the efficacy of abemaciclib for recurrent oligodendroglioma. The primary endpoint is the progression-free survival status of the subject at 6 months after enrollment (PFS-6). The alternative hypothesis is that the proportion of subjects without an event at 6 months will be ³85%. We will test this hypothesis against a null hypothesis of PFS-6 = 50%. With enrollment of 10 planned subjects, the power to detect this difference is 82% (one-sided alpha = 0.05).
Baseline and Increases in Serum B-Cell Maturation Antigen Levels Rapidly Indicate Changes in Clinical Status Among Relapsed/Refractory Multiple Myeloma Patients Undergoing New Treatments
Authors: Sean Bujarski, Kyle Udd, Camilia Soof, Tanya M. Spektor, Tahmineh Safaie, Haiming Chen, Mingjie Li, Eric Sanchez, Joshua Stern, Cathy S. Wang, Ning Xu, Marsiye Emamy-Sadr, Regina Swift, Ashkon Rahbari, Saurabh Patil, Eric Souther, James R. Berenson
Journal: Blood (2019)
COMP-06. PROBING GLIOBLASTOMA AND ITS MICROENVIRONMENT USING SINGLE-NUCLEUS AND SINGLE-CELL SEQUENCING
Authors: Sen Peng, Sanhita Rath, Connor Vuong, Saumya Bollam, Jenny Eschbacher, Shwetal Mehta, Nader Sanai, Seungchan Kim, Michael Berens, Harshil Dhruv
Journal: Neuro-Oncology (2019)

Abstract Single-cell (scSeq) and single-nucleus sequencing (snSeq) are powerful tools to investigate cancer genomics at single cell resolution. Multiple studies have recently illuminated intratumoral heterogeneity in glioblastoma, however, the majority focused on molecular complexity of tumor cells, without taking into account unexplored host cell types that contribute to the microenvironment around tumor. To address the glioblastoma microenvironment composition and potential tumor-host interactions, we performed deep coverage sequencing of freshly resected primary GBM patient tissue without implementing any tumor enrichment strategies. The sequencing resulted in 902 cells and 1186 nuclei, respectively, passing quality control and with low mitochondrial gene percentage. We customized reference transcriptome by listing gene transcript loci as exons to take into account immature RNA, which greatly improved the alignment rate for single-nucleus data. We applied Cell Ranger pipelines (Version 3.0.2) and Seurat package (Version 2.3.1) and discovered 10 clusters in both scSEQ and snSEQ. Pathway analysis of each cluster signature in scSeq data along with known GBM microenvironment cell signatures revealed glioma tumor population along with surrounding microglia/macrophages, astrocytes, pericytes, oligodendrocytes, T cells and endothelial cells. The analysis of snSEQ was able to capture the majority of cell types from patient tissues (tumor and microenvironment cells), but interestingly presented different cell type composition in microenvironment cell types such as microglia/marcophages. Integrating single-cell and single-nucleus transcriptomic data using canonical correlation analysis facilitated a comparison of snSEQ and scSEQ, contrasting depiction for certain cell types (e.g. NKX6-2 gene in Oligodendrocytes). Differential analysis of pathways between tumor and microenvironment cells unveiled potentially rewired pathways such as double strand break repair pathway. Our results demonstrate the cellular diversity of brain tumor microenvironment and lay a foundation to further investigate the individual tumor and host cell transcriptomes that are influenced not only by their cell identity but also by their interaction with surrounding microenvironment.
Redirecting T-Cells Against AML in a Multidimensional Targeting Space Using T-Cell Engaging Antibody Circuits (TEAC)
Authors: Eleanor Minogue, David Millar, Yan Chuan, Songfa Zhang, Korneel Grauwet, Mei Guo, Adam Langenbucher, Cyril H Benes, James Heather, Jeremy Minshull, Michael S. Lawrence, Rupa Narayan, David M. Langenau, Timothy A. Graubert, Mark Cobbold
Journal: Blood (2019)
Penetrance Estimates Over Time to First and Second Primary Cancer Diagnosis in Families with Li-Fraumeni Syndrome: A Single Institution Perspective
Authors: Seung Jun Shin, Elissa B. Dodd-Eaton, Fan Gao, Jasmina Bojadzieva, Jingxiao Chen, Xianhua Kong, Christopher I. Amos, Jing Ning, Louise C. Strong, Wenyi Wang
Journal: Cancer Research (2019)

Abstract Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder associated with TP53 germline mutations and an increased lifetime risk of multiple primary cancers (MPC). Penetrance estimation of time to first and second primary cancer within LFS remains challenging because of limited data and the difficulty of characterizing the effects of a primary cancer on the penetrance of a second primary cancer. Using a recurrent events survival modeling approach that incorporates a family-wise likelihood to efficiently integrate the pedigree structure, we estimated the penetrance for both first and second primary cancer diagnosis from a pediatric sarcoma cohort at MD Anderson Cancer Center [MDACC, Houston, TX; number of families = 189; single primary cancer (SPC) = 771; and MPC = 87]. Validation of the risk prediction performance was performed using an independent MDACC clinical cohort of TP53 tested individuals (SPC = 102 and MPC = 58). These findings showed that an individual diagnosed at a later age was more likely to be diagnosed with a second primary cancer. In addition, TP53 mutation carriers had a HR of 1.65 (95% confidence interval, 1.1–2.5) for developing a second primary cancer versus SPC. The area under the ROC (AUC) curve for predicting individual outcomes of MPC versus SPC was 0.77. In summary, we provide the first set of penetrance estimates for first and second primary cancer for TP53 germline mutation carriers and demonstrate its accuracy for cancer risk assessment. Significance: These findings present an open-source R package LFSPRO that could be used for genetic counseling and health management of individuals with LFS as it estimates the risk of both first and second primary cancer diagnosis. See related article by Shin et al., p. 354
Insidious Cerebrovascular Disease—The Uncool Iceberg
Authors: Juan-Camilo Vargas-González, Vladimir Hachinski
Journal: JAMA Neurology (2019)

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 Neurology 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 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 Neurology journal
Protein Structural Information and Evolutionary Landscape by In Vitro Evolution
Authors: Marco Fantini, Simonetta Lisi, Paolo De Los Rios, Antonino Cattaneo, Annalisa Pastore
Journal: Molecular Biology and Evolution (2019)

Protein structure is tightly intertwined with function according to the laws of evolution. Understanding how structure determines function has been the aim of structural biology for decades. Here, we have wondered instead whether it is possible to exploit the function for which a protein was evolutionary selected to gain information on protein structure and on the landscape explored during the early stages of molecular and natural evolution. To answer to this question, we developed a new methodology, which we named CAMELS (Coupling Analysis by Molecular Evolution Library Sequencing), that is able to obtain the in vitro evolution of a protein from an artificial selection based on function. We were able to observe with CAMELS many features of the TEM-1 beta-lactamase local fold exclusively by generating and sequencing large libraries of mutational variants. We demonstrated that we can, whenever a functional phenotypic selection of a protein is available, sketch the structural and evolutionary landscape of a protein without utilizing purified proteins, collecting physical measurements, or relying on the pool of natural protein variants.
Reply letter to: “A commentary on “minimally invasive percutaneous nephrolithotomy versus retrograde intrarenal surgery in surgical management of upper urinary stones - A systematic review with meta-analysis” (Int J Surg 2019;71:1–11)”
Authors: Binbin Jiao, Zhenkai Luo, Guan Zhang, Shicong Lai
Journal: International Journal of Surgery (2019)
Leveraging the Power of Marginal Gains to Improve Outcomes in Interventional Cardiology
Authors: Matheen A. Khuddus, Alexander G. Truesdell, Ajay J. Kirtane
Journal: JAMA Cardiology (2019)

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 Cardiology 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 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 Cardiology journal
Post Induction and Post Consolidation Measurable/Minimal Residual Disease Predict Relapse in NPM-1 Positive AML. Outcome of Treatment Relapse. a Single Center Experience
Authors: Erika Borlenghi, Chiara Pagani, Michele Malagola, Diego Bertoli, Francesca Schieppati, Silvana Archetti, Angela Passi, Cinzia Lamorgese, Chiara Cattaneo, Nicola Polverelli, Margherita Sciumé, Rosa Daffini, Doriana Gramegna, Mirella Marini, Giuseppe Rossi
Journal: Blood (2019)
NIMG-11. VISUALIZATION OF JUDGMENT BASIS OF CNN TO GRADING GLIOMA
Authors: Satoshi Takahashi, Shota Tanaka, Masamichi Takahashi, Erika Yamazawa, Taijun Hana, Yosuke Kitagawa, Shunsaku Takayanagi, Wataru Takahashi, Takahiro Nakamoto, Akihirio Haga, Ryuji Hamamoto, Nobuhito Saito
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND convolutional neural network (CNN) model using MRI imaging are likely to be effective for grading glioma. However, interpretation of the judgment basis of CNN is difficult. The purpose of this study is twofold. One is to create a high accuracy machine learning model that grading of glioma (Glioma grade II, between III and IV). The other is to visualize the judgment basis of the model. METHODS We targeted cases that were imaged at our Hospital during the period from August 2014 to January 2018. Five types of MRI are used. The five types are two types of DWI (b1000DWI and b2000DWI, respectively, with a value of 1000 and 2000), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and mean kurtosis (MK). The images were input to CNN wtihout ROI. Seven types of CNN were prepared, and 100 epochs of learning were performed. RESULTS 55 cases were included. There were 14 grade II, 12 grade III, and 29 grade IV). Of these, 44 cases up to July 2017 in chronological order were used as a dataset for learning, and 11 cases from August 2017 to January 2018 were taken as independent test dataset. The best results were obtained using MK as input, with a percentage of correct cases of test data of 0.82. Subsequently, we applied Grad-CAM to the model. Grad-CAM is visualized technique that shows where CNN focused on. The model focused on the tumor part of the image. In addition, in the cases of glioma and meningioma coexisting, grading was performed focusing on the glioma area not on meningioma area. CONCLUSION When grading glioma, it was considered that CNN decide glioma’s grade focusing on tumor part of the image, as well as humans.
BrUOG 345: Fractionated Gemtuzumab Ozogamicin Followed By Non-Engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
Authors: Adam Zayac, Pamela C Egan, Thomas A Ollila, Adam J Olszewski, Peter Barth, Matthew I. Quesenberry, James Butera, Loren D. Fast, Rabin Niroula, Peter J. Quesenberry, John L Reagan
Journal: Blood (2019)
Reduced Toxicity Conditioning for Non-Malignant Hematopoietic Cell Transplants
Authors: Cristina F Contreras, Janel R Long-Boyle, Kristin A. Shimano, Jasmeen Dara, James N Huang, Sandhya Kharbanda, Alexis Melton, Christine Higham, Morton J Cowan, Christopher C. Dvorak
Journal: Blood (2019)
Central Nervous System Involvement in Peripheral T-Cell Lymphoma
Authors: Sangeetha Gandhi, N. Nora Bennani, Sonia Fortin, Thomas M. Habermann, Patrick Johnston, James R. Cerhan, Kay M. Ristow, Carrie A. Thompson, Grzegorz Nowakowski, Yi Lin, Jose C Villasboas, Luis Porrata, Thomas E. Witzig, Ivana Micallef, David J Inwards, Stephen M Ansell, Jonas Paludo
Journal: Blood (2019)
External Validation of the Impede VTE Risk Score in Newly Diagnosed Multiple Myeloma (MM) Patients
Authors: Fahrettin Covut, Ramsha Ahmed, Christy J. Samaras, Faiz Anwer, Alex V. Mejia Garcia, Dana E Angelini, Beth M. Faiman, Janice Reed, Mary Ann Karam, Kristen Schlueter, Saveta Mathur, Kimberly Hamilton, Nathaniel Rosko, Jason Valent, Jack Khouri
Journal: Blood (2019)
GENE-61. METHYLATION-BASED LIQUID BIOPSY OF MENINGIOMA PRIMARY AND RECURRENT SAMPLES
Authors: Thais Sarraf Sabedot, Tathiane Malta, James Snyder, Tobias Walbert, Ian Lee, Steven Kalkanis, Anavaleria Castro, Houtan Noushmehr
Journal: Neuro-Oncology (2019)

Abstract Meningiomas are mostly benign CNS tumors, however a subset of these tumors may become atypical or malignant. The standard of care to monitor patients after diagnosis requires serial MRI assessments, which have limited value in distinguishing malignant tumors from benign disease. Therefore the discovery of non-invasive methodologies that reflect meningioma tumor burden and its dynamic evolution in real-time is highly desirable. Liquid biopsy (LB) could be used to fine-tune surveillance and treatment with minimal risk to patients. Evidence of circulating tumor cells and cell-free (cf) tumor DNA in the blood has been shown in several tumor types, however limited progress has been made for brain tumors with known biomarkers; possibly due to the unlikelihood of capturing point mutations in circulating DNA fragments. On the other hand, DNA methylation signatures are maintained even in small DNA fragments, which suggests that DNA methylation is an attractive marker to be studied in liquid biopsy of brain cancers. In order to identify DNA methylation-based biomarkers using archival serum and tissue specimens, we analyzed the epigenome (Illumina Human EPIC array) of patients with primary (n=10) and recurrent (n=4) meningiomas and epileptic patients (n=5) as control. cfDNA fragment size distribution revealed peaks with 150~200bp on average. We identified 482 CpGs (p-value&lt; 0.001) differentially methylated between primary meningiomas and controls, which 294 (61%) show a DNA methylation profile similar to the matched tumor tissue. Overall, we observed that recurrent samples are hypermethylated (56%) compared to primary. From this pilot data, we were able to investigate the LB methylome of meningioma patients and identify potential markers to detect tumor cells in the serum of these patients, which could eventually allow clinicians to monitor impending disease progression and recurrence.
Antidepressant Drugs and Liver Damage
Authors: E. Saphier
Journal: BMJ (1964)

MEBDCLOUUpast year.It is remarkable that this has been achieved without accurate proof of specific pathological damage by these drugs.It is more remarkable that the Witts and Dunlop Committees have issued guidance to the profession on these matters without in- cluding any psychiatrist among their num- bers.This unusual attitude is placing psychiatrists in an extremely difficult posi- tion.It does not seem to be realized adequately enough that there are now more psychiatrists than general physicians, and that psychiatric disorders account for the bulk of general practice.It is most remark-
Effectiveness and Safety of Direct Oral Anticoagulants Vs. Low Molecular Weight Heparin As Anticoagulant Therapy in Patients with Active Cancer Therapy and Non Valvular Atrial Fibrillation
Authors: Pável E Olivera, César A Velasquez, Desirée Campoy, Gonzalo Artaza, Tania Canals, Katia Flores, Silvia Ruiz, Alessandra Comai, Erik A Johansson, Gabriela S Ene, Gabriela Bastidas, Maricel Subira, Jorge Sierra, Ramón Salinas
Journal: Blood (2019)
Nicholas David Carr
Authors: John Beynon, John Hobbiss
Journal: BMJ (2019)

It is with great sadness that we mark the passing of Nicholas David Carr (“Nick”), a former president of the Association of Coloproctology of Great Britain and Ireland (ACPGBI). Nick was born in Leeds, Yorkshire, England. He was educated at Queen Elizabeth Grammar School in Wakefield and did his undergraduate medical training at Bristol University. He undertook senior house officer posts at the Bristol Royal Infirmary before becoming registrar in surgery on the south Manchester circuit. He worked at Withington and Stepping Hill hospitals and as research registrar to Philip Schofield from 1981 to 1983.

He was the recipient of the John of Arderne medal (coloproctology section of the Royal Society of Medicine) in …
Dysregulation of Splicing Patterns in MDS Induced By the S100A9/Fto Axis
Authors: Erika Adriana Eksioglu, Ling Cen, Xianghong Chen, Pingyan Cheng, Kenneth Wright, Thu Le Trinh, Danielle Gilvary, Wendy Kandell, Jinhong Liu, Yin-Kai Chen, Amy F McLemore, Alexandra Calescibetta, John Cleveland, Alan F. List, Sheng Wei
Journal: Blood (2019)
Combined Reductions of the Lower Jaw and Nose
Authors: P. Clarkson, W. Grossman, F. A. Walker
Journal: BMJ (1951)

MEDICALSJOHRNAL.~~~~~~~~~~~~~~~~~~~~~~~~~~~~E IA of eucortone given intravenously are suggested.WVhen improvement in the patient's condition occurs, repeated injections, p&rhaps six-hourly or even four-hourly, may be required at first.The duration of the benefit obtained, however, will be the best guide to the frequency of injection.SummaryFour cases of bilateral suprarenal haemorrhage in association with pregnancy are described.The pathology, clinical features, and diagnosis of the condition are described and suggestions made' for treatment.Stress is laid on pre-eclamptic toxaemia as an aetiological factor during pregnancy.The variability of the' clinical picture is emphasized.The condition often simulates an acute abdominal catastrophe, and in pregnancy the appearances may suggest an accidentad haemorrhage or uterine rupture or inversion.The diagnosis should be remembered in the rare instances when the expected lesion is not found on examination or at laparotomy, or when the patient is not responding to appro- priate conservative treatment.I should like to express my thanks to Dr. Robert Newton for permission to record these cases and to Dr. E.
CSIG-23. NOTCH ACTIVATION INDUCED BY HSV-1 ENCODED miRNA-H16 SENSITIZES oHSV-TREATED TUMORS TO NOTCH INHIBITOR
Authors: Yoshihiro Otani, Ji Young Yoo, Samantha Chao, Joseph Liu, Alena Cristina Jaime-Ramirez, Tae Jin Lee, Brian Hurwitz, Yuanqing Yan, Hongsheng Dai, Joseph C Glorioso, Michael A Caligiuri, Jianhua Yu, Balveen Kaur
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Glioblastomas (GBMs) are resistant to traditional therapies, and new treatment is urgently needed. NOTCH signaling is highly activated in glioma and activated NOTCH signaling is associated with increased tumor growth and therapeutic resistance. Effect of oncolytic virus therapy on NOTCH signaling activation has not been reported to our knowledge. METHODS Western blotting, real time Q-PCR, reporter assay, and bioluminescence mice imaging were used to evaluate oHSV-mediated activation of NOTCH signaling. High throughput analysis of HSV-1-encoded microRNAs and genes were performed to identify the activator of NOTCH signaling, and in silico analysis, 3’ untranslated region (3’UTR) assay, and immunoprecipitation were used to uncover the down-stream signaling. Anti-tumor efficacy of NOTCH inhibitor, gamma-secretase inhibitor (GSI) combined with oHSV was evaluated using intracranial glioma-bearing mouse xenografts. RESULTS oHSV infection induced NOTCH activity in glioma PDX cells. High throughput analysis uncovered this to be due to HSV-1-encoded miR-H16 (miR-H16). 3’UTR analysis of Factor Inhibiting HIF-1 (FIH-1) indicated miR-H16 directly target FIH-1 and repress its protein expression. Immunoprecipitation analysis also uncovered that FIH-1 reduction liberated Mild bomb 1 (Mib1) from FIH-1 mediated sequestration, permitting it to activate NOTCH signaling by ubiquitination of NOTCH ligands. Forced expression of either antago-miR-H16 or FIH-1 attenuated the oHSV-induced NOTCH activation. Furthermore, oHSV therapy-induced activation of NOTCH signaling sensitized tumors to GSI, resulting in significantly improved therapeutic response to oHSV therapy and prolonged the survival in several intracranial GBM xenografts. CONCLUSION In this study, we identified the mechanism of oHSV therapy-mediated activation of NOTCH signaling, and showed the therapeutic benefit of combining oHSV with GSI.