tbuckley/cabot-search huggingface dataset:
A New Molecular Variant in the PTGS1 Gene That Abrogates Generation of Thromboxane A2 Synthesis and Associates with Platelet Dysfunction and Bleeding
Authors: Veronica Palma-Barqueros, Melissa Chan, Marilena Crescente, Jose Maria Bastida, Elena Almarza, Sara Suarez Varela, Cristina Mesa-Núñez, Ignacio Casas-Avilés, Natalia Bohdan, Jf Ruiz-Pividal, Jose Padilla, Nuria Revilla Calvo, A Marín-Quilez, Marta Martín Izquierdo, Rocio Benito, Vicente Vicente, Juan A. Bueren, Jesus Maria . Hernández-Rivas, José Ramón González-Porras, ML Edin, DC Zelding, Tim Warner, Jose Rivera, Maria Luisa Lozano
Journal: Blood (2019)
A Phase 1 Study of Milademetan in Combination with Quizartinib in Patients with Newly Diagnosed (ND) or Relapsed/Refractory (R/R) FLT3-ITD Acute Myeloid Leukemia (AML)
Authors: Naval G. Daver, Weiguo Zhang, Richard Graydon, Vikas K Dawra, Jingdong Xie, Prasanna Kumar, Michael Andreeff
Journal: Blood (2019)
PD2.06 EGFR Inhibitors + Bevacizumab Demonstrated Superior Efficacy Compared with EGFR Inhibitors Alone as First-line Treatment in Advanced NSCLC Patients with EGFR Mutations and BIM Deletion Polymorphisms
Authors: A.F. Cardona, O. Arrieta, A. Ruiz-Patiño, L. Zatarain Barron, L. Corrales-Rodriguez, C. Martín, F. Barrón, C. Sotelo, J. Rodríguez, L. Ricaurte, J. Ávila, D. Mayorga, P. Archila, J. Otero, H. Freitas, V.C. Cordeiro De Lima, L. Mas, H. Carranza, C. Vargas, R. Rosell
Journal: Journal of Thoracic Oncology (2019)
Variation in post-colonoscopy colorectal cancer across colonoscopy providers in English National Health Service: population based cohort study
Authors: Nicholas E Burr, Edmund Derbyshire, John Taylor, Simon Whalley, Venkataraman Subramanian, Paul J Finan, Matthew D Rutter, Roland Valori, Eva J A Morris
Journal: BMJ (2019)

Abstract Objectives To quantify post-colonoscopy colorectal cancer (PCCRC) rates in England by using recent World Endoscopy Organisation guidelines, compare incidence among colonoscopy providers, and explore associated factors that could benefit from quality improvement initiatives. Design Population based cohort study. Setting National Health Service in England between 2005 and 2013. Population All people undergoing colonoscopy and subsequently diagnosed as having colorectal cancer up to three years after their investigation (PCCRC-3yr). Main outcome measures National trends in incidence of PCCRC (within 6-36 months of colonoscopy), univariable and multivariable analyses to explore factors associated with occurrence, and funnel plots to measure variation among providers. Results The overall unadjusted PCCRC-3yr rate was 7.4% (9317/126 152), which decreased from 9.0% in 2005 to 6.5% in 2013 (P&lt;0.01). Rates were lower for colonoscopies performed under the NHS bowel cancer screening programme (593/16 640, 3.6%), while they were higher for those conducted by non-NHS providers (187/2009, 9.3%). Rates were higher in women, in older age groups, and in people with inflammatory bowel disease or diverticular disease, in those with higher comorbidity scores, and in people with previous cancers. Substantial variation in rates among colonoscopy providers remained after adjustment for case mix. Conclusions Wide variation exists in PCCRC-3yr rates across NHS colonoscopy providers in England. The lowest incidence was seen in colonoscopies performed under the NHS bowel cancer screening programme. Quality improvement initiatives are needed to address this variation in rates and prevent colorectal cancer by enabling earlier diagnosis, removing premalignant polyps, and therefore improving outcomes.
Saving those who can't wait
Authors: Are Martin Holm, Jens Gottlieb
Journal: European Respiratory Journal (2019)

<b>For the terminally ill, waiting for a suitable organ for a life-saving transplant may take time. In this issue of the <i>ERJ</i>, the results of the French system for prioritising the urgently ill are reported, and this commentary compares it with other systems.</b>http://bit.ly/2Zw0IaX
Telomeric Length to Characterize and Prognosticate Bone Marrow Failure, Risk of Clonal Evolution and Multi-System Complications in Aplastic Anemia and Other Hypocellular Cytopenic Disorders, Independent of Telomere Gene Complex Mutations
Authors: Shreyans Gandhi, Jie Jiang, Simon Slade, Austin Kulasekararaj, Victoria Potter, Varun Mehra, Petra Muus, Andrea Da Silva, Sudarshan Gurung, Alice Mason, Aytug Kizilors, Nicholas Lea, Sahar Mansour, Robin M. Ireland, Ghulam J. Mufti, Judith Marsh
Journal: Blood (2019)
Albumin nanocomposites with MnO2/Gd2O3 motifs for precise MR imaging of acute myocardial infarction in rabbit models
Authors: Fang Wang, Linyi Wen, Jing Liu, Wanlin Peng, Zihan Meng, Qixian Chen, Yao Wang, Bowen Ke, Yingkun Guo, Peng Mi
Journal: Biomaterials (2019)
INNV-32. SUPER-INDUCTION OF IMMUNOSUPPRESSIVE GLIOBLASTOMA EXTRACELLULAR VESICLES BY IFN-γ
Authors: Mi-Yeon Jung, Benjamin Himes, Luz Cumba-Garcia, Ian Parney
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Median survival is 15 months despite surgery, radiation, and chemotherapy. Immunotherapy is promising but GBM-mediated immunosuppression remains a barrier. Recently, extracellular vesicles (EVs) have been implicated in GBM-mediated immunosuppression through expression of the immune checkpoint molecule PD-L1. Data from our group has suggested this is predominantly through induction of immunosuppressive monocytes including myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs). PD-L1 expression is increased in most nucleated cells following IFN-γ exposure. We, therefore, sought to determine if IFN-γ exposure would result in super-induction of immunosuppressive GBM EVs. EVs were harvested in vitro from matched differentiated and stem-like human GBM cell lines +/- IFN-γ. IFN-γ exposure did not alter EV production or expression of common EV markers but increased PD-L1 expression in EVs from differentiated but not stem-like GBM cells. In keeping with our earlier findings, no direct inhibition of T cell proliferation by stem-like or differentiated GBM EVs was observed regardless of IFN-γ exposure or PD-L1 expression. In contrast, differentiated but not stem-like GBM cell EVs induced MDSC and NCM differentiation from normal monocytes. This was increased following IFN-γ exposure and was dependent upon PD-L1 expression. Monocytes exposed to differentiated but not stem-like GBM cell EVs inhibited T cell proliferation in a similar manner (increased with IFN-γ exposure, decreased with PD-L1 knockdown). Thus, IFN-γ exposure results in super-induction of immunosuppressive EVs from differentiated but not stem-like GBM cells that increase MDSC and NCM differentiation in normal monocytes and increase their ability to inhibit T cell proliferation. These effects are dependent upon PD-L1 up-regulation induced by IFN-γ. This may be an important mechanism GBMs utilize to suppress anti-tumor T cell responses that are typically accompanied by increased IFN-γ expression.
NEK2 Promotes Bortezomib Resistance through Enhancing Autophagy By Upregulation of Beclin1 in Multiple Myeloma Cells
Authors: Jiliang Xia, Yanjuan He, Bin Meng, Jingyu Zhang, Xuan Wu, Xiangling Feng, Chunmei Kuang, Jiaojiao Guo, Yinghong Zhu, Qian Lei, Yongjun Guan, Yi Shen, Lugui Qiu, Wen Zhou
Journal: Blood (2019)
Association of rs363293 single nucleotide polymorphism in promoter region of miRNA-143/145 with susceptibility to colorectal cancer and with patients’ outcome
Authors: G.M. Mihaylova, D. Ivanova, R. Manev, O. Tasinov, N. Nazifova-Tasinova, V. Petrova, D. Petkova- Nelova, Z. Mihaylova, N. Conev, I. Donev, M. Radanova
Journal: Annals of Oncology (2019)
More Considerations on Both Model Assumptions and Results Interpretations—Evaluating Readmission
Authors: Chengan Du, Guohai Zhou, Shu-Xia Li
Journal: JAMA Internal Medicine (2019)

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Genomic Profiling in Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS) Following HMA Failure: Baseline Results from the Inspire Study (04-30)
Authors: Guillermo Garcia-Manero, Anna Jonasova, Selina M. Luger, Aref Al-Kali, David Valcárcel, Erica D. Warlick, Wieslaw W. Jedrzejczak, María Díez-Campelo, Patrick S. Zbyszewski, Christopher Cavanaugh, Richard C. Woodman, Steven M. Fruchtman, Koichi Takahashi
Journal: Blood (2019)
ATIM-02. A NEW SOURCE OF NEOANTIGENS FOR PEDIATRIC AND ADULT BRAIN CANCER VACCINES
Authors: Stephen Albert Johnston, Milene Peterson, Chris Diehnelt, Luhui Shen
Journal: Neuro-Oncology (2019)

Abstract The paucity of mutations in pediatric and adult brain tumors has limited the ability to design therapeutic personal cancer vaccines. However, we have discovered that, in contrast to mutations in DNA, RNA is a rich source of frameshift neoantigens produced by mis-splicing of exons or indels from transcription through micro satellites. We have found that in GBM there are an average of 4000 such FS neoantigens per patient and in DIPG an average of at least 500 FS neoantigens/patient. Approximately 20% of these neoantigens are frequently recurrent across different patients. This has allowed us to design pre-synthesized vaccines for each tumor type. The vaccines consist of 20 -30 FS epitopes that are predicted to be present in at least 20% of all patient’s tumor. Each patient would have a 90% chance of having at least 50% of the peptides in their tumor. This type of “FAST” vaccine is much less expensive than a personal vaccine, any patient could be treated and there would be no delay in producing the vaccine. We have directly compared the efficacy of a FAST and personal vaccines in a mouse model of breast cancer. We find that both approaches have comparable protection though there are some interesting differences. We suggest that FAST vaccines may be a useful approach to developing therapeutic vaccines for brain cancers. We also demonstrate that an array of the 400K possible FS neoantigen peptides can be used to assay which neoantigens the patient has developed antibodies to. This array was useful in discovering the FAST vaccine components and could also be used to determine the pre-existing overlap of a FAST vaccine with the patient’s immune response.
A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide with or without Pomalidomide in Patients with Relapsed and Refractory Multiple Myeloma
Authors: Michael Sebag, Nizar J. Bahlis, Christopher P. Venner, Arleigh McCurdy, C. Tom Kouroukis, Jesse Shustik, Rami Kotb, Darrell J White, Julie Stakiw, Nicole B. Laferriere, Anthony Reiman, Fernando Camacho, Molei Fu, Engin Gul, Donna E. Reece
Journal: Blood (2020)
Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity
Authors: Richie D. Barclay, Joseph W. Beals, Jenny Drnevich, Brian S. Imai, Peter M. Yau, Alexander V. Ulanov, Neale A. Tillin, Martha Villegas-Montes, Scott A. Paluska, Peter W. Watt, Michael De Lisio, Nicholas A. Burd, Richard W. Mackenzie
Journal: Metabolism (2019)
QOLP-11. PSYCHOSOCIAL IMPAIRMENT IN PEDIATRIC NEURO-ONCOLOGY PATIENTS AND THEIR CAREGIVERS
Authors: Trisha Kissoon, Jennifer Fisher, Sridharan Gururangan
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Complex multi-modality treatment for children with brain tumors can cause major distress for patients and caregivers. Active coordination of medical and psychosocial services can improve QoL for affected patients and their caregivers. Few studies have evaluated manifestations of psychosocial distress in pediatric neuro-oncology patients and their caregivers. OBJECTIVE We aim to describe symptoms of psychosocial impairment in children with brain tumors and their caregivers in order to identify possible actionable determinants of psychological wellness. METHODS Children older than 3 years of age diagnosed with a malignant brain tumor receiving care at a large tertiary center and their caregivers underwent psychosocial assessment using the Kessler-10 and the Pediatric Symptoms Checklist. Questionnaires were voluntarily completed at routine visits. Rates of primary outcomes, patient and caregiver distress as defined by the respective scoring scales, were calculated for both groups. Correlation between patient and caregiver distress was evaluated with a Spearman’s Rho calculation. RESULTS A total of 30 patient-caregiver dyads consented to participation and 60 total questionnaires were analyzed. Median patient age was 10 years. 80% of caregivers (N= 24/30) scored high for symptoms of psychological illness on Kessler-10 assessments. Patients exhibited substantial psychosocial impairment in physical (N= 22/30), emotional (N= 18/30), cognitive (N= 12/30), and social (N= 26/30) subdomains of the PSC. There was a significant correlation between clinical manifestations of patient and caregiver psychosocial distress, specifically with regards to symptoms of anxiety (p &lt; 0.05) and depression (p &lt; 0.05). CONCLUSIONS Pediatric neuro-oncology patients and caregivers report considerable levels of psychosocial impairment, particularly in physical, cognitive, emotional, and social function, as well as fatigue and insomnia. The majority of patients and caregivers exhibited coinciding symptoms, suggesting that family-based intervention may improve psychosocial stressors. This hypothesis requires future study to determine optimal timing and methods for intervention.
GPR108 Is a Highly Conserved AAV Entry Factor
Authors: Amanda M. Dudek, Nerea Zabaleta, Eric Zinn, Sirika Pillay, James Zengel, Caryn Porter, Jennifer Santos Franceschini, Reynette Estelien, Jan E. Carette, Guo Ling Zhou, Luk H. Vandenberghe
Journal: Molecular Therapy (2019)

Adeno-associated virus (AAV) is a highly promising gene transfer vector, yet major cellular requirements for AAV entry are poorly understood. Using a genome-wide CRISPR screen for entry of evolutionarily divergent serotype AAVrh32.33, we identified GPR108, a member of the G protein-coupled receptor superfamily, as an AAV entry factor. Of greater than 20 divergent AAVs across all AAV clades tested in human cell lines, only AAV5 transduction was unaffected in the GPR108 knockout (KO). GPR108 dependency was further shown in murine and primary cells in vitro. These findings are further validated in vivo, as the Gpr108 KO mouse demonstrates 10- to 100-fold reduced expression for AAV8 and rh32.33 but not AAV5. Mechanistically, both GPR108 N- and C-terminal domains are required for transduction, and on the capsid, a VP1 unique domain that is not conserved on AAV5 can be transferred to confer GPR108 independence onto AAV2 chimeras. In vitro binding and fractionation studies indicate reduced nuclear import and cytosolic accumulation in the absence of GPR108. We thus have identified the second of two AAV entry factors that is conserved between mice and humans relevant both in vitro and in vivo, further providing a mechanistic understanding to the tropism of AAV gene therapy vectors.Graphical abstract
PDCT-12. CLINICAL EFFICACY OF ONC201 IN THALAMIC H3 K27M-MUTANT GLIOMA
Authors: Abed Rahman Kawakibi, Sharon Gardner, Andrew Chi, Sylvia Kurz, Patrick Wen, Isabel Arrillaga-Romany, Tracy Batchelor, Nicholas Butowski, Ashley Sumrall, Nicole Shonka, Rebecca Harrison, John DeGroot, Minesh Mehta, Yazmin Odia, Matthew Hall, Doured Daghistani, Timothy Cloughesy, Benjamin Ellingson, Yoshie Umemura, Jonathan Schwartz, Vivekanand Yadav, Rodrigo Cartaxo, Zachary Miklja, Amy Bruzek, Ruby Siada, Brendan Mullan, Stefanie Stallard, Ashwath Muruganand, Kyle Wierzbicki, Alyssa Paul, Ian Wolfe, Chandan Kumar-Sinha, Bernard Marini, Marcia Leonard, Hugh Garton, Rajen Mody, Patricia Robertson, Krystal Merdinger, Rohinton Tarapore, Wolfgang Oster, Joshua Allen, Carl Koschmann
Journal: Neuro-Oncology (2019)

Abstract ONC201, the first bitopic DRD2 antagonist for clinical oncology, has shown efficacy in H3 K27M-mutant glioma. We performed an integrated preclinical and clinical analysis of ONC201 in thalamic H3 K27M-mutant glioma. ONC201 was effective in mouse intra-uterine electroporation (IUE)-generated H3 K27M-mutant gliomas, with an in vitro IC50 of 500 nM and 50% prolongation of median survival in vivo (p=0.02, n=14). Elevated DRD2 expression was found in the thalamus of non-malignant brain tissue, leading to the hypothesis that thalamic tumors may be a particularly ONC201-sensitive sub-group. We analyzed thalamic H3 K27M-mutant glioma patients treated with ONC201 as of the 05/22/2019 cutoff date, which included patients who had recurrent disease prior to initiating ONC201 (n=20; 15–73 years old) and post-radiation non-recurrent patients (n=11; 5–19 years old). As of 5/22/2019, 10 of 20 recurrent patients and 9 of 11 non-recurrent patients remain on-treatment. Median PFS has not been reached for either cohort: median follow-up of 2.2 months (range: 0.6–37.9) for recurrent patients and 10.6 months (range: 4.3–20.5) from diagnosis for non-recurrent patients. Best response so far by RANO includes 1 CR, 2 PR, 7 SD, 9 PD, 1 NE for recurrent patients and 1 PR, 7 SD, 3 PD for non-recurrent patients. Additionally, 3 recurrent (-66%, -47%, -34%) and 2 non-recurrent (-40%, -10%) patients experienced regressions but are not yet confirmed PRs. For recurrent patients, median onset of response is 3.5 months (range: 2.2–3.8) and median duration of response has not been reached with a median follow-up of 12.5 months (range: 8.1–32.8). Preliminary analyses demonstrated a strong correlation of cell-free tumor DNA in plasma and CSF with MRI response. In summary, ONC201 demonstrates promising clinical efficacy in thalamic H3 K27M-mutant glioma patients, regardless of age. Micro-environmental DRD2 expression may enhance the overall ONC201 response and extend its therapeutic utility beyond H3 K27M-mutant glioma.
Determinants of Clinical Trial Participation and Impact on Survival Outcomes Among Patients with Newly Diagnosed Multiple Myeloma
Authors: Gabriella C Malave, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, Suzanne R. Hayman, David Dingli, Francis K. Buadi, Eli Muchtar, Wilson I Gonsalves, Nelson Leung, Ronald S. Go, Mustaqeem Siddiqui, Taxiarchis Kourelis, Rahma M Warsame, Yi Lin, Stephen J Russell, Yi L. Hwa, Miriam A. Hobbs, Amie Fonder, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood (2019)
GENE-11. LDSCORE REGRESSION IDENTIFIES NOVEL ASSOCIATIONS BETWEEN GLIOMA AND AUTO-IMMUNE CONDITIONS
Authors: Quinn Ostrom, Jacob Edelson, Jinyoung Byun, Younghun Han, Kyle Walsh, Christopher Amos, Melissa Bondy
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Prior epidemiological studies in glioma have identified 25 germline risk variants, as well as risk associations with exposure to ionizing radiation (which increases risk) and history of allergies and aspirin use (which decrease risk). In this analysis we LDscore regression, which leverages single SNP associations and known patterns of linkage disequilibrium (LD) to estimate the genetic correlation between phenotypes, to confirm prior associations as well as attempt to identify novel phenotype associations for traits not previously assessed that may improve genetic prediction for glioma. METHODS Summary statistics for all glioma, GBM, and non-GBM were obtained from a prior meta-analysis conducted by Melin, et al. Summary statistics for 13 immune- and atopy-related traits were obtained from the prior case-control studies and the UK biobank. Data were filtered to include only SNPs with imputation INFO value &gt;0.7, and minor allele frequency &gt;0.01, excluding SNPs within the HLA region. Pairwise genetic correlation between these traits was generated using LDSC. Associations were considered significant at p&lt; 0.05 RESULTS Significant negative correlations were identified between glioma and ulcerative colitis (rg= -0.4039, p=4.91x10-10), celiac disease (rg= -0.2028, p=1.18x10-4), lupus (rg= -0.0956, p=0.0083), and multiple sclerosis (rg= -0.5755, p=4.46x10-9). These associations were generally consistent in both GBM and non-GBM. There was a significant correlation between both self-reported (rg= -0.102, p=0.0233) and doctor diagnosed (rg= -0.116, p=0.0305) hayfever/allergic rhinitis and GBM only. CONCLUSIONS This analysis demonstrates a genetic basis for previously identified protective effect of allergic rhinitis on GBM, and identifies novel associations between multiple auto-immune traits and glioma. Further studies are necessary in order to confirm these associations and identify the mechanism through which increased immune activity may lower risk of glioma.
Peripheral Neuropathy and Hypovitaminosis D Are Associated in Multiple Myeloma Patients
Authors: Berdien Oortgiesen, Hans Kroes, Petra Scholtens, Jitske Hoogland, Pauline Dannenberg-de Keijzer, Claire Siemes, Frank Jansman, Robby Kibbelaar, Nic Veeger, Mels Hoogendoorn, Eric van Roon
Journal: Blood (2019)