tbuckley/cabot-search huggingface dataset:
A randomized trial of a nurse-led decision aid to inform patients with advanced cancer about palliative chemotherapy.
Authors: P. B. Ottevanger, Linda JM Oostendorp, Winette T.A. Van Der Graaf, Peep FM Stalmeier
Journal: Journal of Clinical Oncology (2013)

e20583 Background: There is a lack of decision aids (DAs) for patients with advanced cancer considering palliative treatment. In this randomized study, we evaluated nurse-led DAs about second-line palliative chemotherapy for patients with advanced breast (BC) or colorectal cancer (CRC). Methods: Patients with advanced BC or CRC considering second-line treatment were randomized to receive only usual care (control group) or usual care plus a DA from a nurse (intervention group) (1:2 ratio). Using the DA, a nurse offered information on adverse events, tumor response, and survival. Patients completed a baseline questionnaire and two follow-up questionnaires 1 week and 8 weeks after the treatment-related information was provided. Outcome measures were well-being, coping, knowledge, and information and decision-related outcomes. Intent-to-treat analyses were performed using Chi Square tests, independent samples t-tests, and linear mixed models to examine differences between groups over time. Results: In all,128 patients participated in the study; median age 62 years (range 32-81), 37% male, 73% CRC. Of the 83 patients assigned to the intervention group, 77 received a DA. At the first follow-up, more patients receiving a DA preferred chemotherapy (96% vs. 84%; p=0.067). Seven weeks later, 88% of patients in the intervention group and 84% of patients in the control group had started chemotherapy (p=0.746). The only statistically significant effect was the stronger treatment preference of patients in the intervention group (3.0 vs. 2.5; p=0.030). The DAs did not negatively impact anxiety, depression, cancer worries, and hopelessness. Conclusions: It is possible to offer a DA with explicit information to patients with advanced cancer without negative impact on patients' well-being. Unexpectedly, this study did not show consistent effectiveness of the DAs. Our interpretation is that most patients receiving the DA had already decided to start chemotherapy. Clinical trial information: NTR1113.
The Use of Venetoclax for Acute Myeloid Leukemia in a Real-Life Setting: A Multicenter National Experience
Authors: Jacopo Nanni, Giacomo Gianfaldoni, Gianluca Cristiano, Giovanni Marconi, Matteo Piccini, Pietro Grieco, Sofia Pilerci, Michele Gottardi, Marco Cerrano, Sarah Parisi, Chiara Sartor, Emanuela Ottaviani, Lorenza Baldini, Nicoletta Testoni, Carmen Baldazzi, Stefania Paolini, Filippo Gherlinzoni, Alberto Bosi, Mario Boccadoro, Michele Cavo, Cristina Papayannidis, Antonio Curti
Journal: Blood (2019)
Evolution of Epistatic Networks and the Genetic Basis of Innate Behaviors
Authors: Robert R.H. Anholt
Journal: Trends in Genetics (2019)

Instinctive behaviors are genetically programmed behaviors that occur independent of experience. How genetic programs that give rise to the manifestation of such behaviors evolve remains an unresolved question. I propose that evolution of species-specific innate behaviors is accomplished through progressive modifications of pre-existing genetic networks composed of allelic variants. I hypothesize that changes in frequencies of one or more constituent allelic variants within the network leads to changes in gene network connectivity and the emergence of a reorganized network that can support the emergence of a novel behavioral phenotype and becomes stabilized when key allelic variants are driven to fixation.
EXTH-61. CELECOXIB IMPROVES OUTCOME OF PATIENTS TREATED WITH TUMOR TREATING FIELDS
Authors: Eric Wong, Oliver Xu, Mercedes Riley, Kenneth Swanson
Journal: Neuro-Oncology (2019)

Abstract Tumor Treating Fields (TTFields) are known to cause mitotic catastrophe resulting in aberrant mitotic exit. However, there is accumulating evidence that the clinical effectiveness of TTFields requires immune competence. Exposure of cells to TTFields induced signs of cellular stress including cytoskeletal changes, surface expression of calreticulin and secretion of HMGB1 suggesting that TTFields may promote anti-tumor immunity that leads to subsequent tumor regression. Many tumor-protective mechanisms require immunosuppressive cell types within the tumor microenvironment whose development and suppressive functions are supported by prostaglandin E2 (PGE2). The rate limiting enzyme for PGE2 production is Cyclooxygenases-2 (COX-2) whose upregulation has been correlated with poor survival in glioma patients. Therefore, we reasoned that reduction of PGE2 production within the tumor microenvironment might improve response to TTFields therapy. Previous data from our group indicated that dexamethasone use interfered with TTFields-efficacy. When our population having low dexamethasone usage (n=42) was dichotomized according to celecoxib use, those without celecoxib (n = 14) had a median overall survival (OS) of 8.1 months while those receiving celecoxib had a median OS of 12.9 months (chi-square 5.42, p=0.002, HR = 2.1, 95% CI = 1.19–5.59). Patients not receiving celecoxib were treated with TTFields for a median of 3.8 months while those receiving celecoxib were treated for a median of 8.2 months (Chi-square = 6.75, p = 0.01, HR = 2.3, CI = 1.33–6.47). These data suggest that the addition of celecoxib improved the efficacy of TTFields against glioblastoma in this cohort. However, celecoxib did not sensitize TTFields-induced killing of cells in vitro suggesting an indirect mechanism of action. Together with our in vitro data, the results support an immune mechanism of action underlying TTFields’ anti-tumor efficacy. These findings concerning the effects of celecoxib on patient outcomes need to be confirmed in a prospective clinical trial.
PDTM-22. A C19MC-LIN28A-MYCN ONCOGENIC CIRCUIT DRIVEN BY HIJACKED SUPER-ENHANCERS IS A DISTINCT THERAPEUTIC VULNERABILITY IN ETMRS – A LETHAL BRAIN TUMOR
Authors: Iqra Mumal, Patrick Sin-Chan, Tannu Suwal, Irtisha Singh, Xiao-Nan Li, Charles Lin, Jeremy Rich, Stephen Mack, Annie Huang
Journal: Neuro-Oncology (2019)

Abstract Embryonal tumors with multi-layered rosettes (ETMR) are aggressive brain cancers with characteristic C19MC oncomiR amplification and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a potent C19MC-LIN28A-MYCN circuitry driven by multiple regulatory loops and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. C19MC and LIN28A targets respectively converge on critical cell cycle tumor suppressors and neo-embryonic DNMT3A/B isoforms. We identify a MYCN driven, core transcriptional network, conserved in early neural stem cells, that is potently abrogated by treatment with bromodomain inhibitor JQ1, leading to ETMR cell death. Our collective data suggest C19MC oncomiRs drive a malignant primitive cell state in ETMRs via entrapment of an early neural lineage network, which represents a critical therapeutic vulnerability for this recalcitrant disease.
Telephone or internet delivered talking therapy can alleviate irritable bowel symptoms
Authors: Rob Cook, Peter Davidson, Rosie Martin
Journal: BMJ (2019)

The study Everitt H, Landau G, Little P. Therapist telephone-delivered CBT and web-based CBT compared with treatment as usual in refractory irritable bowel syndrome: the ACTIB three-arm RCT. Health Technol Assess 2019;23:1-154. This project was funded by the NIHR Health Technology Assessment Programme (project number 11/69/02). To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000784/irritable-bowel-syndrome-helped-by-telephone-or-internet-cbt
An Open-Label, Phase 2 Study of KRT-232, a First-in-Class, Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients with Myelofibrosis (MF) Who Have Previously Received Treatment with a JAK Inhibitor
Authors: Regina Garcia-Delgado, Donal P. McLornan, László Rejtő, Eric Jourdan, Haifa Kathrin Al-Ali, Andrzej Pluta, Marek Hus, Joanne Ewing, Irum Khan, Holger Hebart, Philipp J. Jost, Sebastian Grosicki, Wayne M. Rothbaum, Jesse McGreivy, Srdan Verstovsek
Journal: Blood (2019)
Comparison of Minimal Residual Disease Detection between the Manual and Automated Gating Strategies of Euroflow Next-Generation Flow in Patients with Multiple Myeloma
Authors: Hiroyuki Takamatsu, Takeshi Yoroidaka, Takeshi Yamashita, Ryoichi Murata, Mikio Ueda, Shinji Nakao, Kosei Matsue
Journal: Blood (2019)
INNV-28. MOLECULAR TESTING IN NEURO-ONCOLOGY – ASSESSMENT OF UTILITY AND PRACTICE PATTERNS. A SOCIETY FOR NEURO-ONCOLOGY MEMBERSHIP SURVEY
Authors: Maciej Mrugala, Susan Chang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. Multiple molecular panels are available providing a spectrum of information. We were interested in learning how this information is acquired, what are the practice patterns regarding this type of testing, how are the results utilized in patient care and how prepared neuro-oncologists are to interpret these results. METHODS We conducted a survey using the Society for Neuro-Oncology membership database. We developed a set of 13 questions and administered the survey to 2022 members using the online platform. RESULTS We received 153 responses (7.5% of membership). 89% percent of responders routinely order MT. Of those who do not order MT on all patients, 50% test younger patients and 57% midline tumors. 83% use MT in recurrent glioma. Other common indications for MT included: metastatic tumors, meningioma, medulloblastoma, ATRT. Majority (60%) use in-house panels, followed by Foundation One (35%), TEMPUS (13%), CARIS (10%) and other panels (23%). For 57% of respondents, the data from MT was somewhat useful and for 41% it was very useful. 78% used the results of MT for clinical decision-making. BRAF, EGFR/ALK, H3K27 mutations were most commonly used for treatment decisions. 50% of respondents have molecular tumor boards at their institutions and a majority of practitioners share the results of MT with their patients (95%). Respondents would like to see SNO-endorsed official guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials and more educational programs on the subject. CONCLUSIONS Molecular testing is neuro-oncology is commonly done. Many providers rely on the information for clinical decision making where appropriate. In-house and commercial genetic panels are equally used in practice. There continues to be a need for more education on the subject and development of neuro-oncology specific guidelines.
Ponatinib Treatment in CML and Ph+ ALL Patients: Real-Life Data from the Czech Registries
Authors: Eva Koriťáková, Michael Doubek, Edgar Faber, Daniela Žáčková, Jan M. Horáček, Petra Bělohlávková, Eduard Cmunt, František Folber, Pavel Jindra, Hana Klamová, Zdeněk Kořístek, Lukáš Stejskal, Tomáš Szotkowski, Cyril Šálek, Renata Kellnerová, Marika Chrápavá
Journal: Blood (2019)
T‐cell receptor repertoire data provides new evidence for hygiene hypothesis of allergic diseases
Authors: Ke Cao, Jinghua Wu, Xuemei Li, Hua Xie, Chenling Tang, Xiaodong Zhao, Shiyu Wang, Liping Chen, Wei Zhang, Yunfei An, Xin Li, Liya Lin, Ruonan Chai, Mingyan Fang, Yuanhang Yue, Xie Wang, Yuan Ding, Lina Zhou, Qin Zhao, Huanming Yang, Jian Wang, Shaoheng He, Xiao Liu
Journal: Allergy (2019)

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IMMU-24. A COMPREHENSIVE IN SILICO APPROACH TO DISCOVERING TUMOR REJECTION ANTIGENS IN MALIGNANT BRAIN TUMORS
Authors: Changlin Yang, Kyle Dyson, Oleg Yegorov, Duane Mitchell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Proteins that can serve as effective tumor rejection antigens within brain tumors are poorly characterized. Current prediction algorithms relying on identification of mutated epitopes as neoantigens are limited in low mutational burden tumors. We have developed a multi-faceted computer algorighm for identifying tumor rejection antigens called the Open Reading Frame Antigen Network (ORAN). This pipeline provides a comprehensive solution for predicting brain tumor immunogenic targetable epitopes/transcripts. METHODS Human and murine RNASeq and WES data were QCed. Patients individual HLA-I and HLA-II haplotypes were predicted by highly customized Optitype and Phlat Algorithms. SNPs and Indels were called from tumors WES and read through matched RNASeq data. 19,131 transcripts expression were counted per TOIL algorithm. Tumor associate antigens(TAA) of individual patient or murine tumors were selected by setting a cutoff of Transcripts Per Million (TPM) &gt; 1 on individual patient’s tumor, while RNA Seq data from 7000 normal tissues was used to identify tumor unique transcripts. Actual sequence of HLA and SNPed Consenses TAA(CTAA) were called. Only expressed mutations and personalized TAAs were used for antigenic epitope predictions. All neoepitopes were screened against a human reference proteomic library to guarantee that epitopes were not shared by other expressed isoforms or genes. In silico validation were preformed to cross validate predictions made by ORAN. RESULTS In medullobastoma (N=121 samples), ORAN gives an average of 15.6 MHC class I restricted neoepitopes,11.9 epitopes encoded by Indels and with 33.2 MHC class II restricted neoepitopes and 16.2 Indel antigens per patient. The TAAs of each patient reaches average 256 antigenic epitopes per patient. ORAN also predicts the exact HLA and neo-antigens from a validated neoantigens vaccine dataset (Gros A Nat Med 2016). CONCLUSION ORAN accurately identifies validated neoantigens and provides a comprehensive list of potential tumor rejection antigens within human and murine brain tumors.
Platelet and Immune Characteristics of Patients with Immune Thrombocytopaenia Non Responders to Therapeutic Treatments
Authors: Elena Monzón Manzano, Raul Justo Sanz, Diana Hernández, Teresa Álvarez Roman, Ihosvany Fernandez-Bello, Mónica Martín, Larissa Valor, María Isabel Rivas Pollmar, Miguel A Canales, Victor Jimenez-Yuste, Nora Butta
Journal: Blood (2019)
Assessment of Bleeding Phenotype in Hemophilia Α By a Novel Point-of-Care Global Assay
Authors: Debnath Maji, Michael A Suster, Divyaswathi Citla Sridhar, Maria Alejandra Pereda, Janet Martin, Lalitha V. Nayak, Pedram Mohseni, Sanjay P Ahuja
Journal: Blood (2019)
Prophylactic or Preemptive Low-Dose Azacitidine (AZA) and Donor Lymphocyte Infusion (DLI) Prevent Disease Relapse Following Allogeneic Transplantation in High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Thierry Guillaume, Pierre Peterlin, Sylvain Thepot, Amandine Le Bourgeois, Alice Garnier, Sylvie François, Corentin Orvain, Yannick Le Bris, Clémentine Fronteau, Patrice Chevallier
Journal: Blood (2019)
RTHP-27. RARE INTRACRANIAL PRIMARY YOLK SAC TUMORS IN ADOLESCENT PATIENTS: A REPORT OF 10 CASES DEPARTMENT OF ONCOLOGY
Authors: Weiping Hong, Yanying Yang, Linbo Cai
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To retrospective analyze 10 patients with intracranial primary yolk sac tumors(YST) for exploring an optimal treatment strategy. METHODS Ten patients with YST were confirmed by pathological diagnosis (9 male and 1 female), with a median age of 13 years. Except for 1 case was lost to follow-up, 9 patients were treated with partial resection, followed by WBRT and local boosts, and then adjuvant chemotherapy. The time it took for serum AFP to decrease to the lowest level (including abnormal situation) or to return to the normal level was recorded. The brain tumor apoplexies before and after treatment were studied. Finally, OS and PFS of the patients were analyzed. RESULTS The patients were followed-up to 02-2019, with a mean follow-up time of 25.44 months. The analysis showed that the mOS and mPFS were 18 months and 7 months, respectively, and that 1y-OS and 2y-OS were 77.8% and 22.2%, while 1y-PFS and 2y-PFS were 22.2% and 11.1%. The time it took for serum AFP to decrease to the lowest level or to return to the normal level was 0–382 days, with a median time of 144 days (165.22±131.71 days). After being followed-up to 02-2019, 4 patients still survived; 4 patients died of tumor recurrence; 1 patient died of severe pneumonia. Although one of the 4 patients (tumor recurrence) was treated with 3 times of surgeries, died of tumor progression, with a survival time of 17 months. The other one patient had a 1y-PFS of 3 months, and he received surgery and chemotherapy for recurrent tumors, achieving a 2y-PFS up to 71+ months. CONCLUSION YST has a low incidence rate and is easy to recurrence, with a poor prognosis. Resection combined with chemoradiotherapy can prolong the survival time of patients, but the optimal treatment strategy remains unclear and needs further research.
Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology
Authors: Nadeem R. Abu-Rustum, Catheryn M. Yashar, Sarah Bean, Kristin Bradley, Susana M. Campos, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Rachel Sisodia, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Nicole R. McMillian, Jillian Scavone
Journal: Journal of the National Comprehensive Cancer Network (2019)

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.
Provision of Insurance Coverage for IVF by a Large Employer and Changes in IVF Rates Among Health Plan Enrollees
Authors: James M. Dupree, Zachary Levinson, Angela S. Kelley, Marsha Manning, Vanessa K. Dalton, Helen Levy, Richard A. Hirth
Journal: JAMA (2019)

This study investigates changes in in vitro fertilization (IVF) rates among health plan enrollees between 2012 and 2017 after a large US empoloyer (University of Michigan) began providing coverage for IVF in 2015.
Diarrhoea and Vomiting
Authors: E. Clayton-Jones
Journal: BMJ (1956)

Diarrhoea and VomitingSIR,-The epidemics of "D. and V.," such as we used to have towards the end of every summer when I first went to Guy's Hospital as a student in 1924, are now fairly rare; and when outbreaks or odd cases do arise, despite the vastly improved hygiene and relative opulence of to-day, the patients' chances of recovery are no longer hopeless, as they were nine times out of ten in those days-far from it, for there is often a choice of several treatments nowadays, all nearly equally effective.That was a disease of older infants-6 to 18 months or so-a true "cholera infantum," though the cholera vibrio threw in its hand when its watery hiding-place was revealed in the "Broad Street pump" outbreak of 1854.
Teaching general practice.
Authors: G Fowler
Journal: BMJ (1977)

3) Dr Woodcock's point about the effect of the failure rate had been considered.In any experimentation on human subjects missing data from subject loss tend to occur; there is no way of completely overcoming this problem, either clinically or statistically.We believe our analysis provided the most reasoned assessment of the data by (1) analysing between group failure rates and (2) analysing the exist- ing data while explicitly acknowledging the possible effects of missing data.Furthermore, both sets of data are presented and both show small positive effects for antimicrobials, so there is little chance of the reader beirng misled.
SURG-12. “NANOPASTE” THERAPY AS POTENTIAL TREATMENT OPTION FOR RECURRENT GLIOBLASTOMA
Authors: Michael Schwake, Oliver Grauer, Markus Holling, Benjamin Brokinkel, Michael Müther, Ann-Katrin Bruns, Johannes Wölfer, Walter Stummer
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND We recently showed that intracavitary thermotherapy with superparamagnetic iron-oxide nanoparticles can induce persistent inflammatory reactions which might lead to long-term stabilization in recurrent glioblastoma (GBM) patients. METHODS Here, we report further data from a series of ten recurrent GBM WHO IV patients (IDH WT, MGMT: methylated 30%, unmethylated 70%; median age: 59 years) who were treated with intracavitary thermotherapy after coating the resection cavity wall (“NanoPaste”) with NanoTherm® particles (MagForce AG, Berlin, Germany). All patients underwent six one-hour semi-weekly hyperthermia sessions in an alternating magnetic field (mean maximum temperature 52.3° C, SD +/- 6.0 °C). Six patients received concurrent radiotherapy at a dose of 39.6 Gy (5 x 1.8 Gy/week). RESULTS No major side effects were observed during active treatment. However, all patients developed cerebral edema and increasing clinical symptoms during treatment follow-up (median 92 days, range 73 to 144). Patients were treated with dexamethasone and, if necessary, underwent re-operation to remove nanoparticles (n=5). Histopathology revealed sustained necrosis and large amounts of nanoparticles without evidence for tumor activity as well as a prominent inflammatory reaction characterized by increased T-cell and myeloid cell infiltration. Median overall survival (mOS) for the study population was 10.1 months (CI 95% 8.0–12.2). A survival benefit was observed for patients treated at first recurrence (n=5) when compared to patients treated at second recurrence or later (mOS = 20.6 vs 9.4 months). Patients who received thermotherapy and concurrent radiotherapy (n=6) showed longer mOS than patients treated with thermotherapy alone (17.3 vs 8.6 months). Two patients had long-lasting treatment responses &gt; 23 months with one patient still alive at 3.5 years after treatment without receiving any further therapy. CONCLUSION Our results warrant further investigations. A European clinical registry will be rolled out to further evaluate the potential of “NanoPaste” therapy for patients with recurrent glioblastoma.
Incidental Pulmonary Embolism. Analysis of Mayo Clinic Venous Thromboembolism Database
Authors: Ewa Wysokinska, Damon E. Houghton, Danielle Vlazny, Aneel A. Ashrani, David A Froehling, David O. Hodge, Lisa Peterson, Robert D. McBane, Waldemar E. Wysokinski, Ana I Casanegra
Journal: Blood (2019)
Reversible TET Inhibitor As a Hematopoietic Stem Cell Booster: A Novel Strategy to Improve Stem Cell Function
Authors: Sunisa Kongkiatkamon, Yihong Guan, Anand Tiwari, Phillip J Maciejewski, Dale Grabowski, Sergei Vatolin, Vera Adema, Cassandra M Kerr, Yasunobu Nagata, Milo Co, Christina Snider, Hassan Awada, Jibran Durrani, Yvonne Parker, Daniel J. Lindner, Mikkael A. Sekeres, Valeria Visconte, James G Phillips, Jaroslaw P. Maciejewski, Babal K. Jha
Journal: Blood (2019)