tbuckley/cabot-search huggingface dataset:
Giving all registrars a fair chance of becoming consultants
Authors: H. Didier
Journal: BMJ (1981)

<h3>Abstract</h3> <h3>Motivation</h3> Drug combination therapy has become a increasingly promising method in the treatment of cancer. However, the number of possible drug combinations is so huge that it is hard to screen synergistic drug combinations through wet-lab experiments. Therefore, computational screening has become an important way to prioritize drug combinations. Graph neural network have recently shown remarkable performance in the prediction of compound-protein interactions, but it has not been applied to the screening of drug combinations. <h3>Results</h3> In this paper, we proposed a deep learning model based on graph neural networks and attention mechanism to identify drug combinations that can effectively inhibit the viability of specific cancer cells. The feature embeddings of drug molecule structure and gene expression profiles were taken as input to multi-layer feedforward neural network to identify the synergistic drug combinations. We compared DeepDDS with classical machine learning methods and other deep learning-based methods on benchmark data set, and the leave-one-out experimental results showed that DeepDDS achieved better performance than competitive methods. Also, on an independent test set released by well-known pharmaceutical enterprise AstraZeneca, DeepDDS was superior to competitive methods by more than 16% predictive precision. Furthermore, we explored the interpretability of the graph attention network, and found the correlation matrix of atomic features revealed important chemical substructures of drugs. We believed that DeepDDS is an effective tool that prioritized synergistic drug combinations for further wet-lab experiment validation. <h3>Availability and implementation</h3> Source code and data are available at https://github.com/Sinwang404/DeepDDS/tree/master
Improving timely access to food allergy care: A pragmatic controlled trial
Authors: Harriet Hiscock, Prescilla Perera, Margaret H. Danchin, Valerie Sung, Katherine Lee, Chiara Stival, Rebecca Peat, John Molloy, Sharoan Selvakumaran, Mimi L. K. Tang
Journal: Allergy (2019)

The authors have no conflicts of interest relevant to this article to disclose. Deidentified individual participant data will not be made available. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Assessment of Citations of the Retracted Article by Wakefield et al With Fraudulent Claims of an Association Between Vaccination and Autism
Authors: Elizabeth M. Suelzer, Jennifer Deal, Karen L. Hanus, Barbara Ruggeri, Rita Sieracki, Elizabeth Witkowski
Journal: JAMA Network Open (2019)

The number of citations can be used to show the influence of an article or to measure the validity of a research study. The article by Wakefield et al that fraudulently reported an association between vaccination and autism continues to accumulate citations even after it was retracted.To examine the characteristics of citations from scholarly literature that reference the 1998 article by Wakefield et al and to investigate whether authors are accurately citing retracted references.In this cross-sectional bibliographic analysis of the scholarly publications that cited a 1998 article by Wakefield et al, cited references were collected from a Web of Science Core Collection search performed on March 11, 2019. A total of 1211 articles were identified, with 58 citing works excluded because they were non-English-language publications or the citation to the study by Wakefield et al could not be located by reviewers. Citing works consisted of books, research articles, letters, editorials, news items, and other scholarly literature. Citations to the article by Wakefield et al were identified and analyzed by 2 reviewers in a blinded screening. Reviewers assigned a characteristic to each citation and indicated whether the retraction was documented.The characteristics of citations to the article by Wakefield et al, were categorized as negative, affirmative, or contrastive; if not, persuasive; and if not, assumptive, perfunctory, methodologic, or conceptual. Whether the partial retraction or notice of retraction was included in the citing work was also documented.Among the 1153 citing works included in this analysis, the most common citation characteristics were negative (838 [72.7%]) followed by perfunctory (106 [9.2%]) and affirmative (94 [8.2%]). A total of 123 of 322 citing works (38.2%) published between 2005 and 2010 documented the partial retraction. After the notice of retraction was published in 2010, the percentage of citing works that documented the partial retraction and/or notice of retraction between 2011 and 2018 increased to 360 of 502 (71.7%).Since the article by Wakefield et al was initially published, authors have mostly negated the findings of the study. A significant number of authors did not document retractions of the article by Wakefield et al. The findings suggest that improvements are needed from publishers, bibliographic databases, and citation management software to ensure that retracted articles are accurately documented.
Single-Antibody Detection of T-Cell Receptor Beta Chain Monotypia Resolves Uncertainties in the Identification and Quantitation of Sézary Cells By Routine Flow Cytometry: Towards Accurate and Unequivocal Blood Staging of Cutaneous T-Cell Lymphomas
Authors: Pedro Horna, Min Shi, Dragan Jevremovic, Horatiu Olteanu
Journal: Blood (2019)
TMOD-03. SOMATIC MUTATIONS OF CHROMATIN REGULATOR Kmt2d IN CEREBELLAR PRECURSORS INFLUENCES SHH-MEDULLOBLASTOMA TUMORIGENESIS
Authors: Reeti Sanghrajka, I-li Tan, Alexandre Wojcinski, Harikrishna Rallapalli, Daniel Turnbull, Kai Ge, Alexandra Joyner
Journal: Neuro-Oncology (2019)

Abstract Medulloblastoma (MB), the most common malignant pediatric brain tumor, is a classic example of dysregulation of developmental pathways leading to tumorogenesis. Despite advancements in multi-modal therapies, most patients suffer from long-term neurocognitive and neuroendocrine disabilities. The Sonic Hedgehog subgroup of MB (SHH-MB) accounts for ~30% of all cases and originates from ATOH1+ cerebellar granule cell precursors (GCPs). Experimental data in mice has shown that activating mutations in the SHH pathway induce tumors only in rare GCPs, suggesting that additional mutations and epigenetic changes are required to influence tumor progression. The KMT2D gene, encoding the histone-lysine N-methyltransferase 2D, is amongst the ten most frequently mutated genes in MB, with somatic mutations seen in ~15% of all SHH-MB patients. We developed sporadic mouse models of SHH-MB with a low penetrance to enable studies of secondary mutations (Tan, PNAS, 2018). Immunofluorescence staining for KMT2D on early-stage SHH-MB lesions, mid-stage and late-stage tumors revealed that a subset of lesions/tumors (16/98) do not express KMT2D and are negative for H3K4me3. Interestingly, P53 and KMT2D expression showed a positive correlation in ~94% of tumors/lesions and NeuN and KMT2D showed a positive correlation in ~92% of tumors/lesions. In order to determine the roles for KMT2D in GCP proliferation and differentiation, and uncover whether and how KMT2D promotes SHH-MB tumorigenesis, we are using genetic mouse-models whereby Kmt2d is heterozygously or homozygously deleted alone, or in conjunction with activation of the SHH pathway. Mice with SHH-MB tumors expressing SmoM2 and a loss of Kmt2d develop aggressive tumors at high penetrance, with metastatic leptomeningeal spread in the brain stem and spinal cord. Thus, loss of Kmt2d increases SHH-MB tumor progression and leads to malignancy. Ongoing studies are determining how the chromatin landscape and gene expression are changed when Kmt2d is deleted in GCPs.
JX06, a Novel PDK1 Inhibitor, Induces Myeloma Cell Apoptosis By Metabolic Reprogramming and Works Synergistically with Bortezomib
Authors: Takayuki Sasano, Saki Kushima, Matsushita Yutaka, Masao Matsuoka, Hiroyuki Hata, Yawara Kawano
Journal: Blood (2019)
RTHP-34. IMPROVED SURVIVAL IN CNS LYMPHOMA WITH SALVAGE LOW-DOSE WHOLE-BRAIN RADIOTHERAPY WITH FOCAL BOOST AND CONCURRENT TEMOZOLOMIDE
Authors: Katherine Selwa, Anna Laucis, Theodore Lawrence, Larry Junck, Kyle Cuneo, Michelle Kim, Daniel Wahl, Yoshie Umemura
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE There is no standard salvage radiotherapy (RT) regimen, nor a consensus on the concurrent chemotherapy use in CNS lymphoma. We assessed the efficacy of low-dose whole-brain radiotherapy (WBRT) with focal-boost to the area of disease and concurrent temozolomide for the salvage treatment of CNS lymphoma. METHODS A single center retrospective study of CNS lymphoma patients seen between 01/2004 and 02/2019. The inclusion criteria were: diagnosis of CNS lymphoma, age &gt; 18 years at diagnosis, radiation treatment to the brain, and formulation of plan at University of Michigan with at least one follow-up. Overall survival (OS) was determined by Kaplan Meier method. RESULTS Out of 93 patients (median age 58, 45% female), 73% were diagnosed with primary CNS lymphoma (n=68), and the remainder with secondary CNS lymphoma. Radiation modalities were WBRT alone (n=52), low-dose WBRT + focal boost (n=33) and focal RT alone (n=8). Twenty-six patients (28%) received concurrent temozolomide with radiation. Those who received WBRT+boost achieved complete response at a significantly higher rate than those who received WBRT alone (36% vs 17% respectively, p=0.047). The median OS among all groups was 45 months. There was a significant improvement in OS in patients receiving low-dose WBRT+boost compared to WBRT alone (median 65 vs 14 months respectively, p=0.016). OS was significantly longer in patients who received concurrent temozolomide than in those who did not (median 86 vs 23 months respectively, p=0.0287). CONCLUSIONS In CNS lymphoma salvage RT, a longer survival was observed with low-dose WBRT with focal-boost compared to WBRT alone, as well as with concurrent temozolomide. This result is limited by the selection bias to each of the treatment groups; however, the low-dose WBRT with focal-boost and concurrent temozolomide is a useful salvage alternative to standard WBRT as it may reduce long-term neurocognitive toxicity.
Whole Genome Profiling of Adult B-Other Acute Lymphoblastic Leukaemia on the UKALL14 Trial
Authors: Daniel A. Leongamornlert, Emilio Barretta, Soo Lee, Thomas Creasey, Rachel J. Mitchell, Amy A. Kirkwood, Laura Clifton-Hadley, Pip Patrick, Peter J Campbell, Bela Wrench, Anthony V. Moorman, Adele K. Fielding, Elli Papaemmanuil
Journal: Blood (2019)
Stable Neurocognitive Function with Improvement in Processing Speed Following Haploidentical Bone Marrow Transplant with Post-Transplant Cytoxan in Children and Adolescents with Sickle Cell Disease
Authors: Dilan A Patel, Kemar V Prussien, Karina L Wilkerson, Becky Armstrong, Leena Karnik, Adetola A. Kassim, Josu de la Fuente
Journal: Blood (2019)
Current Treatments Do Not Improve the Prognosis of Patients with Atypical CML and Unclassified MDS/MPN. a Joint Report from Fi-LMC, FIM, Gfch and GFM
Authors: Vaidie Julien, Delphine Rea, Sylvain Thepot, Le Pluart Bruno, Nathalie Gachard, Stéphanie Struski, Lydia Roy, Cecile Bally, Jo Caers, Franck E Nicolini, Bruno Cassinat, Eric Lippert, Laurence Legros, Raphael Itzykson
Journal: Blood (2019)
SCIDOT-27. TGFβ SIGNALING-INDUCED miRNA PARTICIPATES IN AUTOPHAGIC REGULATION BY TARGETING PRAS40 IN MESENCHYMAL SUBTYPE OF GLIOBLASTOMA
Authors: Yingbin Xie, Luyue Chen, Junhu Zhou, Qixue Wang, Yunfei Wang, Yanli Tan, Chunsheng Kang, Chuan Fang
Journal: Neuro-Oncology (2019)

Abstract Mesenchymal subtype of glioblastoma (mesGBM) is a refractory disease condition characterized by therapeutic failure and tumor recurrence, and for the past decade, no treatment option has improved the dismal prognosis of this disease. In Cancer Genome Atlas (TCGA) GBM datasets, two of the 840 transcriptomic signature genes for GBM subtyping, TGFβ1 and TGFβ receptor type II (TβRII), were exclusively upregulated in mesGBM, indicating hyperactive TGFβ signaling. In the present study, dysregulated microRNAs (miRNAs) were identified after LY2109761 (a TβRI/II inhibitor) treatment in a mesGBM-derived cell line. Importantly, several novel miRNAs that may be missing pieces of the puzzle of TGFβ signaling-mediated pathogenesis in mesGBM were identified. Novel_miR26/56/93/97/119 were validated by quantitative PCR to correlate with TGFβ signaling activity, and novel_miR56 was selected as a promising candidate for further functional verification. A proline-rich akt substrate of 40 kDa (PRAS40), which regulates autophagy initiation by targeting mTORC1, was confirmed to be a functional target of novel_miR56. Autophagy plays dichotomous roles in the determination of GBM cell fate, and in this study, TGFβ signaling-induced novel_miR56 seemed to inhibit autophagic activity in GBM and its mesenchymal subtype, resulting in the maintenance of proliferative capability. The pro-survival effect of novel_miR56 can be impeded by intentionally downregulating its expression both in vivo and in vitro. In summary, we provide novel insight into TGFβ signaling-mediated pathogenesis and targets for the development of novel therapeutic interventions for mesGBM.
SCIDOT-40. THERAPEUTIC GENOME EDITING AS A NOVEL TREATMENT FOR GBM
Authors: Daniel Rosenblum, Anna Gutkin, Dan Peer
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma multiforme (GBM), is the most aggressive form of glioma, a brain tumor that arises from glial cells. GBM is considered a complex malignancy with multiple gene mutations, aberrations, and overexpression together with high infiltration rate and resistance to apoptosis. The current treatment consists of surgical resection, aggressive radiation and chemotherapy regimen. This therapeutic strategy had not changed since 2005 when the chemotherapy Temozolomide was approved. This therapeutic approach extended GBM patients’ life expectancy to approximately 15 months since diagnosis. Although recent progress in genomics and proteomics has paved the way for identifying potential therapeutic targets for treating GBM, the majority of these leading drug candidates remain ineffective. Therefore, novel and effective treatment to GBM presents an unmet need. Lipid nanoparticles (LNPs) are the most clinically advanced delivery platform to date for systemic administration of RNA therapeutics, with the recent approval of Patisiran, siRNA encapsulating LNPs. In recent years, several gene editing technologies have been discovered in bacteria, enabling precise and permanent manipulations at the DNA level. The most advanced and versatile system is based on the CRISPR nuclease Cas9. The recognition of its target chromosomal DNA by Cas9 results in a site-specific double-strand break (DSB), that eventually results in gene disruption. This approach opens multiple venues for research and treatment of diseases including cancer. We have utilized CRISPR encapsulating LNPs to promote a therapeutic gene editing by disrupting key GBM survival genes in vitro in murine and human GBM cell lines as well as in vivo in an aggressive syngeneic GBM mouse model. Our results suggest that treatment with our LNPs based system can specifically and efficiently target GBM cells in vitro and in vivo. Our CRISPR-LNPs based platform could potentially mature to a clinical trial, and ultimately might become a new therapeutic modality in GBM.
EXTH-62. STEM CELL DELIVERY OF ONCOLYTIC ADENOVIRUS DNX-2401 FOLLOWING SURGICAL RESECTION FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Sricharan Gopakumar, Joy Gumin, Marc Daou, Daniel Ledbetter, Malcolm McDonald, Anwar Hossain, Shawn Hingtgen, Matthew Ewend, Frederick Lang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The oncolytic virus DNX-2401 (Delta-24-RGD) is a novel treatment of GBM. While prior studies have examined intratumoral injection of DNX-2401 into recurrent GBM, the potential of delivering DNX-2401 into the surgical resection cavity using tumor-tropic human mesenchymal stem cells (MSCs) has not been evaluated. We hypothesize that exploiting a fibrin-based scaffold for transplanting MSCs loaded with DNX-2401 (MSCs-DNX-2401) into the resection cavity will improve viral delivery, decrease GBM recurrence, and extend overall survival. METHODS MSCs-DNX-2401 were seeded in a fibrin matrix or suspended in PBS and placed in the upper wells of transwell plates with U87 cells placed below. After one week, U87 cells were counted to compare rates of cellular killing and confirm release of DNX-2401 from fibrin-seeded MSCs. U87 cells were transduced with mCherry-Luciferase and implanted into the brains of athymic mice (N=16). After fluorescence-guided surgical resection of glioma xenografts, MSCs (control) or MSCs-DNX-2401 were delivered in the resection cavity using a fibrin scaffold. Serial bioluminescence imaging (BLI) was used to monitor tumor recurrence. RESULTS In transwell experiments, MSCs-DNX-2401 seeded in fibrin were as effective as MSCs-DNX-2401 without the scaffold, indicating that fibrin did not negatively impact cell viability or viral release. In in vivo studies mimicking residual tumor after surgical resection, treatment of the post-resection cavity with MSCs-DNX-2401 suspended in fibrin permitted retention of MSCs-DNX-2401 within the tumor bed. Kaplan-Meier survival analyses revealed statistically significant improved survival after treatment with MSC-DNX-2401 in fibrin compared to controls with 50% of animals demonstrating complete responses according to BLI (p &lt; 0.05). CONCLUSION Delivering DNX-2401 into the post-resection surgical cavity using MSCs seeded in fibrin is capable of eradicating residual GBM and prolonging overall survival. These studies support the clinical translation of this approach in newly diagnosed patients undergoing surgical resection of GBM.
QOLP-41. ASSESSING CAREGIVERS’ OF PATIENTS WITH PRIMARY BRAIN TUMORS EXPERIENCES WITH AND NEEDS RELATED TO SEIZURE MANAGEMENT
Authors: Paula Warren, Deborah Ejem, Richard Taylor, Rebecca Edwards, James Dionne-Odom, Louis Nabors, Marie Bakitas
Journal: Neuro-Oncology (2019)

Abstract Family caregivers of persons with primary brain tumors report high levels of distress. Information is limited, however, regarding family caregivers’ experiences and needs concerning the risk and management of seizures in this population. In this qualitative descriptive study, we conducted one-on-one interviews to describe the experiences of family caregivers’ of persons with primary brain tumors who have had and who have not yet had a seizure. We sought information on how they coped with this issue and what information they needed regarding management of out-of-the-hospital seizures. We conducted 15 interviews using study-specific interview protocols; 10 caregivers with seizure experience and 5 caregivers without seizure experience. Caregivers were, on average, 52 years old, predominately white (93.3%), college graduates (66.7%), and were employed full-time (53.3%). The relationship between caregiver and care recipient was spouse (46.7%), other family member (46.7%), and friend (6.6%). Most caregivers provided care everyday (46.7%) and for more than 8 hours per day (33.3%). Themes emerged around three major domains: 1) caregiver challenges regarding seizures, 2) desired resources/information about seizures, and 3) timing of delivery of these resources. Caregivers often reported being fearful of seizures and the majority (93%) expressed difficulty with knowing when to call EMS. In terms of desired resources, opinions were split between preferring written materials versus online resources with most participants (87%) stating that videos or graphics detailing seizures would be helpful. In terms of delivery timing, most (66.7%) thought that training should come after diagnosis versus at the time of diagnosis citing reasons such as too much other information to absorb and overall inability to focus. Future studies will use this information to develop and pilot a seizure-focused supportive caregiver intervention that is tailored and caregiver-directed and that can be incorporated into standard neuro-oncology clinical practice.
A Randomized Phase 2 Trial Comparing Carfilzomib-Dexamethasone Vs Observation As Maintenance after Induction with Carfilzomib-Cyclophosphamide-Dexamethasone in Salvage ASCT in Multiple Myeloma: A Trial By the Nordic Myeloma Study Group
Authors: Henrik Gregersen, Valdas Peceliunas, Kari Remes, Fredrik H. Schjesvold, Niels Abildgaard, Hareth Nahi, Niels Frost Andersen, Annette Juul Vangsted, Tobias Wirenfeldt Klausen, Carsten Helleberg, Kristina Carlson, Ulf Christian Frølund, Per Axelsson, Olga Stromberg, Cecilie Hveding Blimark, Olle Linder, Galina Tsykunova, Anders Waage, Markus Hansson, Nina Gulbrandsen
Journal: Blood (2019)
A Phase II Study of Single-Agent Inotuzumab Ozogamicin in Pediatric CD22-Positive Relapsed/Refractory Acute Lymphoblastic Leukemia: Results of the ITCC-059 Study
Authors: Erica Brivio, Franco Locatelli, Adriana Thano, Arnaud Petit, Britta Julia Vormoor, Susana Rives, Bella Bielorai, Claudia Rossig, Carmelo Rizzari, Vincent H.J. Van Der Velden, Anneke C.J. Ammerlaan, Monique L. Den Boer, Barbara Sleight, Gernot Engstler, Jan Stary, Francisco José Bautista Sirvent, Christiane Chen-Santel, Bénédicte Bruno, Yves Bertrand, Fanny Rialland, Geneviève Plat, Dirk Reinhardt, Luciana Vinti, Arend von Stackelberg, Christian Michel Zwaan
Journal: Blood (2020)
Huntington's Chorea in Northamptonshire
Authors: J. J. A. Reid
Journal: BMJ (1960)

identified in the tumour is injected iron-dextran and not haemosiderin.A random biopsy of skin from the deltoid area of the other arm contained no iron.The possibility that the tumour developed coincidentally at the inoculation site has been considered.It has not been proved that the tumour is primary.
Prognostic Factors for Progression in Patients (pts) with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) in Complete Molecular Response (CMR) within 3 Months of Therapy with Tyrosine Kinase Inhibitors (TKIs)
Authors: Koji Sasaki, Hagop M. Kantarjian, Bachar Samra, Nicholas J. Short, Joseph D. Khoury, Rashmi Kanagal-Shamanna, Marina Y Konopleva, Nitin Jain, Courtney D. DiNardo, Rita Khouri, Guillermo Garcia-Manero, Tapan M. Kadia, William G. Wierda, Nicole Tippett, Rebecca Garris, Victoria Jeanis, Naval G. Daver, Philip A. Thompson, Musa Yilmaz, Jorge E. Cortes, Susan M. O'Brien, Farhad Ravandi, Elias Jabbour
Journal: Blood (2019)