tbuckley/cabot-search huggingface dataset:
Real World Data on Obstetric (OC) and Maternal Complications (MC) Occurring in a Cohort of Patients with Ph Negative Myeloproliferative Neoplasms (MPN): Argentinian Multicentric Study
Authors: Angeles Vicente, Paula G. Heller, Georgina Bendek, Federico Sackmann, Ana Ines Varela, Miguel Castro Rios, Ludmila Elhelou, Verónica Vallejo, Beatriz Moiraghi, Marina Narbaitz, Anahí Vijnovich Baron, Eriberto Roveri, Claudia Casali, Carlos Ponzinibio, Marcelo Iastrebner, María Susana Gomez, Celeste Garcia, Federico Sebastian Peretz, Paula Cardenas, Alicia Enrico, Guillermina Remaggi, Santiago Boughen, Irene Larripa, Emiliano Carricondo, Vanesa Caruso, Mariel Perez, Laura Kornblihtt
Journal: Blood (2019)
Abstract 15194: Dabigatran Causes Remodelling of Plaque Extracellular-Matrix in Diabetogenic Low Density Lipoprotein-Receptor Knockout Mice
Authors: Nadine Nagy, Maria Grandoch, Jens W Fischer
Journal: Circulation (2011)

Thrombin plays a central role in thrombus formation and platelet aggregation and is critically involved in many processes known to promote vascular diseases, e.g. stimulation of smooth muscle cell ...
Cost of drugs prescribed in primary care continues to fall
Authors: Ingrid Torjesen
Journal: BMJ (2019)

The cost of drugs prescribed in primary care fell by 2.8% in 2018-19, data from NHS Digital show.1 Over the same period the cost of drugs prescribed in hospitals rose by 11.1%.

Hospitals accounted for 53.7% (£10.2bn (€11.9bn; $13.2bn)) …
DNA Hypomethylation within B-Cell Enhancers and Super Enhancers Reveal a Dependency on Immune and Metabolic Mechanisms in Chronic Lymphocytic Leukemia
Authors: Austin Y. Shull, Junfeng Luo, Lirong Pei, Eun-Joon Lee, Jimei Liu, Justin Choi, Farrukh T. Awan, Huidong Shi
Journal: Blood (2016)
A RANDOMIZED PHASE II TRIAL OF VELIPARIB (V), RADIOTHERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS (PTS) WITH UNMETHYLATED MGMT (uMGMT) GLIOBLASTOMA (GBM): THE VERTU STUDY
Authors: Mustafa Khasraw, Kerrie Leanne McDonald, Mark Rosenthal, Zarnie Lwin, David Ashley, Helen Wheeler, Elizabeth Barnes, Matthew Foote, Eng-Siew Koh, Erik Sulman, Michael Back, Michael Buckland, Hao-Wen Sim, Lauren Fisher, Robyn Leonard, Merryn Hall, Sonia Yip, John Simes
Journal: Neuro-Oncology (2019)
Glucose 6-Phosphate Accumulates via Phosphoglucose Isomerase Inhibition in Heart Muscle
Authors: Anja Karlstaedt, Radhika Khanna, Manoj Thangam, Heinrich Taegtmeyer
Journal: Circulation Research (2019)

Metabolic and structural remodeling is a hallmark of heart failure. This remodeling involves activation of the mTOR (mammalian target of rapamycin) signaling pathway, but little is known on how intermediary metabolites are integrated as metabolic signals.We investigated the metabolic control of cardiac glycolysis and explored the potential of glucose 6-phosphate (G6P) to regulate glycolytic flux and mTOR activation.We developed a kinetic model of cardiomyocyte carbohydrate metabolism, CardioGlyco, to study the metabolic control of myocardial glycolysis and G6P levels. Metabolic control analysis revealed that G6P concentration is dependent on phosphoglucose isomerase (PGI) activity. Next, we integrated ex vivo tracer studies with mathematical simulations to test how changes in glucose supply and glycolytic flux affect mTOR activation. Nutrient deprivation promoted a tight coupling between glucose uptake and oxidation, G6P reduction, and increased protein-protein interaction between hexokinase II and mTOR. We validated the in silico modeling in cultured adult mouse ventricular cardiomyocytes by modulating PGI activity using erythrose 4-phosphate. Inhibition of glycolytic flux at the level of PGI caused G6P accumulation, which correlated with increased mTOR activation. Using click chemistry, we labeled newly synthesized proteins and confirmed that inhibition of PGI increases protein synthesis.The reduction of PGI activity directly affects myocyte growth by regulating mTOR activation.
Over-Expression of Transferrin Receptor (TFRC/CD71) and Low Expression of Innate and Adaptive Immune Cell Subsets in HIV-Associated, GCB-DLBCL By Digital Gene Expression Profiling
Authors: Alanna Maguire, Xianfeng Chen, Lee Wisner, Colleen Ramsower, Betty Glinsmann-Gibson, Lisa M. Rimsza
Journal: Blood (2019)
EXTH-39. BENCH TO BEDSIDE NEURO-ONCOLOGY: ADVOCATING FOR A CLINICALLY RELEVANT STRATEGY
Authors: Samer Zammar, Dennis Madden, Karisa Schreck, Michael Berens, Jorg Dietrich, Michael Glantz
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Therapeutic successes in neuro-oncology have lagged dramatically behind exciting laboratory discoveries, and successful translation of promising laboratory findings into clinical practice is rare. We hypothesize that one important reason for this discordance is the use of very different paradigms for designing laboratory and clinical trials, and that utilizing clinically relevant procedures could improve laboratory study impact. METHODS We identified all pre-clinical neuro-oncology therapeutic trials published in four high-impact journals between 11/2018 and 4/2019, and assigned a level of evidence (LOE) to each study using the American Academy of Neurology evidence classification system. We also extracted details about statistical techniques, funding, and institutional setting. RESULTS Of the 26 articles identified, 85% had a LOE of IV (highest-I, lowest-IV) and 15% were class III. Factors contributing to the low LOE included lack of randomization (65%) or allocation concealment (100%), absence of masked assessment (96%), and no comparison of treatment and control groups with respect to prognostically relevant characteristics (92%). Effect size and confidence interval reporting, power calculation, correction for multiple hypothesis testing, and multivariate analysis were absent in 92%, 92%, 100%, 88%, and 92% of studies respectively. The “reverse” analysis (starting with successful human trials and analyzing existing pre-clinical support studies) showed significantly more high quality laboratory studies supporting “successful” compared to “unsuccessful” trials (p=0.04). CONCLUSIONS When rigorous human clinical trials criteria are applied to therapeutic laboratory studies, laboratory study LOE is uniformly poor. For laboratory research intended to inform clinical trial design and improve clinical outcomes, this situation dooms most basic science research to fail in the clinical arena. The steps required to solve this problem are challenging but addressable, and costs associated with the solution are dwarfed by the expense of early phase human trials which are destine to failure.
Impact of Primary Antibacterial Prophylaxis on Neutropenic Fever, Infections, and Antimicrobial Resistance in Newly Diagnosed AML Patients
Authors: Jessica Caro, Erin Moshier, Douglas Tremblay, Alexander Coltoff, Guido Lancman, Meenakshi Rana, John Mascarenhas, Samantha Jacobs
Journal: Blood (2019)
Real-World Application of National Comprehensive Cancer Network (NCCN) Testing Guidelines in Diffuse Large B-Cell Lymphoma (DLBCL) Results in Underdiagnosis of Double-Hit Lymphoma
Authors: Ian J. Hooley, Christina M. Parrinello, Adomah S. Opong, Kathleen Maignan, Kenneth R. Carson, Richard I. Fisher
Journal: Blood (2019)
EPID-16. COMPARATIVE ANALYSIS OF OVERALL SURVIVAL AND ADVERSE EVENTS BY ADJUVANT TREATMENT MODALITIES IN ELDERLY PATIENTS WITH GLIOBLASTOMA USING THE SEER-MEDICARE DATABASE
Authors: Ping Zhu, Xianglin Du, Jay-Jiguang Zhu
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES Few studies have investigated the frequency of adverse event (AE) by adjuvant therapy modalities in elderly patients with glioblastoma (GBM) in “real-world” setting. We conducted a retrospective cohort analysis to compare survival differences and incidences of AE with different treatment modalities. METHODS A total of 3100 elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset (2004–2013). Adjuvant therapy modalities were either chemoradiation (CRT) followed by maintenance chemotherapy with temozolomide or RT alone. Primary outcomes include overall survival (OS) and cumulative incidences of 6-month and 1-year AEs with adjuvant therapies. Kaplan-Meier method and Cox proportional hazards regression were applied for survival analysis. Fine-Gray competing risk models were performed to estimate the risk of incident AEs over time with death as the competing risk event. RESULTS Superior OS was observed among GBM patients treated with CRT compared to RT alone (median OS: 6.9 vs. 2.9 months, P&lt; 0.001). In multivariable Cox proportional hazard model, the risk of death was decreased by 52% for patients in the CRT group over the RT alone group (P&lt; 0.001). Based on the multivariable competing risk models, the receipt of CRT was associated with higher risk of incident 6-month AEs with nausea/vomiting [sub-hazard ratio (SHR): 1.82, P=0.003] and constipation (SHR: 1.47, P=0.022); and 1-year AEs with neutropenia (SHR: 1.63, P=0.002), anemia (SHR: 1.64, P&lt; 0.002), DVT (SHR: 1.25, P=0.035), seizure/epilepsy (SHR: 1.47, P=0.001), nausea/vomiting (SHR: 2.08, P&lt; 0.001), diarrhea (SHR: 1.70, P=0.034), gastroenteritis/colitis (SHR: 2.77, P=0.024), constipation (SHR: 1.62, P=0.001), and dehydration (SHR: 1.27, P=0.020). CONCLUSION Comparing to the RT alone group, elderly GBM patients received CRT had 4-month median OS benefit, but experienced significantly higher incidences of AEs.
Epigallocatechin-3-Gallate Induces Cellular Differentiation and Reduces Leukemia Burden in PML/Rarα Mice By Increasing Reactive Oxygen Species and Reducing PIN1 Expression
Authors: Fernanda I Della Via, Rodrigo Naoto Shiraishi, Santos Irene, Karla P Ferro, Myriam Salazar-Terreros, Gilberto C Franchi Junior, Eduardo M Rego, Sara T Olalla Saad, Cristiane Okuda Torello
Journal: Blood (2019)
Use of Maintenance Therapy Post Autologous Stem Cell Transplantation Outside of Clinical Trial Setting for Multiple Myeloma: Single Institution Experience
Authors: Dhauna Karam, Morie A Gertz, Martha Q. Lacy, Angela Dispenzieri, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Taxiarchis Kourelis, Rahma M Warsame, William J Hogan, Shaji K. Kumar
Journal: Blood (2019)
High Diagnostic Utility of Flow Cytometry Based Peripheral Blood Monocyte Subset Analysis, CD56 and CD2 Expression in Chronic Myelomonocytic Leukemia (CMML)
Authors: Xavier Calvo, Ivonne Parraga, Nieves Garcia-Gisbert, Lourdes Florensa, Sara Montesdeoca, Concepción Fernández, Marta Salido, Anna Puiggros, Blanca Espinet, Beatriz Bellosillo, Lluís Colomo, David Roman, Marcio Andrade Campos, Brayan Merchan, Ana Ferrer, Leonor Arenillas
Journal: Blood (2019)
The Mitochondrial Protease, Neurolysin (NLN), Regulates Respiratory Chain Complex and Supercomplex Formation and Is Necessary for AML Viability
Authors: Sara Mirali, Botham Aaron, Veronique Voisin, Changjiang Xu, Jonathan St-Germain, David Sharon, Fieke W Hoff, Yihua Qiu, Rose Hurren, Marcela Gronda, Yulia Jitkova, G Wei Xu, Boaz Nachmias, Neil MacLean, Xiaoming Wang, Andrea Arruda, Mark D. Minden, Terzah M Horton, Steven M. Kornblau, Steven M Chan, Gary D Bader, Brian Raught, Aaron D Schimmer
Journal: Blood (2019)
STEM-16. DUAL INHIBITION OF PROTEIN ARGININE METHYLTRANSFERASE 5 AND PROTEIN PHOSPHATASE 2A ENHANCES THE ANTI-TUMOR EFFICACY IN PRIMARY GLIOBLASTOMA NEUROSPHERES
Authors: Hannah Sur, Arunakumar Gangaplara, Xiang Wang, Abhik Ray-Chaudhury, Zhengping Zhuang, Sachin Kumar, John Heiss, Ji Young Yoo, Balveen Kaur, Yeshavanth Kumar Banasavadi-Siddegowda
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant primary brain tumor and has a heterogeneous tumor cell population. The median survival of GBM patients is less than two years with current multi-model therapy of maximal surgical resection followed by chemotherapy, radiation and tumor treating fields. Protein Arginine Methyltransferase 5 (PRMT5) regulates cellular functions through symmetric di-methylation of arginine residues of histone and non-histone proteins. Our recent findings show that PRMT5 is overexpressed in GBM; its inhibition causes apoptosis and senescence of mature and immature GBM tumor cells respectively. Protein Phosphatase 2A (PP2A), a serine-threonine phosphatase, is associated with senescent tumor cells that contribute to therapy resistance; LB100 is a first-in-class small molecule inhibitor of PP2A that can sensitize tumor cells that are chemo- and radiation-therapy resistant. In this study, using patient-derived primary GBM neurospheres (GBMNS), we tested the anti-GBM effect of concurrent PRMT5 and PP2A inhibition. METHODS Patient-derived primary GBM neurospheres transfected with PRMT5 target-specific siRNA were treated with LB100 and subjected to in vitro assays such as proliferation assay, cell cycle analysis, cytotoxicity assay, PP2A activity and western blot. RESULTS LB100 treatment significantly reduced the viability of PRMT5-depleted GBM cells as compared to PRMT5 intact cells. LB100 caused G1 cell cycle arrest through inactivation of Rb protein; this effect is further enhanced in combination with PRMT5-depletion. Combination therapy also increased the expression of phospho-MLKL; Necrostatin-1 rescued PRMT5-depleted cells from the cytotoxic effects of LB100 indicating that necroptosis caused the enhanced cytotoxicity in combination therapy. We also found that PRMT5-depletion increased the PP2A activity in GBM neurospheres. CONCLUSION Combining the PRMT5 inhibition and PP2A inhibition produced greater antitumor effects than with PRMT5 inhibition alone.
Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity
Authors: Robert C. Kaplan, Zheng Wang, Mykhaylo Usyk, Daniela Sotres-Alvarez, Martha L. Daviglus, Neil Schneiderman, Gregory A. Talavera, Marc D. Gellman, Bharat Thyagarajan, Jee-Young Moon, Yoshiki Vázquez-Baeza, Daniel McDonald, Jessica S. Williams-Nguyen, Michael C. Wu, Kari E. North, Justin Shaffer, Christopher C. Sollecito, Qibin Qi, Carmen R. Isasi, Tao Wang, Rob Knight, Robert D. Burk
Journal: Genome biology (2019)

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.
Catalytic microgelators for decoupled control of gelation rate and rigidity of the biological gels
Authors: Yu-Tong Hong, Daniel T. Bregante, Johnny Ching-Wei Lee, Yongbeom Seo, Dae-Hyun Kim, Yong Jae Lee, Lawrence B. Schook, Hojeong Jeon, Hak-Joon Sung, David W. Flaherty, Simon A. Rogers, Hyunjoon Kong
Journal: Journal of Controlled Release (2019)
CBMT-49. OXALOACETATE ALTERS GLUCOSE METABOLISM IN GLIOBLASTOMA: 13C ISOTOPOMER STUDY
Authors: Omkar Ijare, David Conway, Alan Cash, David Baskin, Kumar Pichumani
Journal: Neuro-Oncology (2019)

Abstract Anhydrous enol-oxaloacetate (AEO) has demonstrated the ability to enhance neuronal cell bioenergetics and activate brain mitochondrial biogenesis. Since oxaloacetate has demonstrated positive effects on brain bioenergetics in neurodegenerative diseases we have begun to investigate whether AEO may also have a positive effect on the altered cellular metabolism found in cancer cells, particularly Glioblastoma multiforme. The “Warburg effect” describes an abnormal metabolic state in cancer, distinct from normal tissue, in which energy is generated through enhanced conversion of pyruvate to lactate even in the presence of oxygen during glycolysis. Oxaloacetate (OAA) is a key anaplerotic substrate that is required to maintain TCA cycle flux. The role of oxaloacetate supplementation on the energy metabolism is not known in cancer cells. Goal of this study is to investigate the changes in metabolic fluxes in glucose metabolism with and without the presence of OAA in patient-derived GBM cells. We use GC-MS based 13C isotopomer analysis for this study. GBM cells are grown in 15mM glucose containing DMEM medium supplemented with 2mM oxaloacetate for 10 days. 6 hours prior to harvesting, [U-13C]glucose is introduced to the medium. 13C isotopomer analysis of GC-MS data showed that OAA supplementation for 10 days drastically decreased Warburg glycolysis by reducing 13C labeling (M+3) by 19.7% and 48.8% in pyruvate and lactate pools respectively in comparison with cells not treated with OAA. M+3 13C labeled pyruvate entered TCA cycle via acetyl-CoA, where we also observed reduced levels of M+2 13C labeled citrate (20.5%) and glutamate (23.9%) isotopomers. Pyruvate can also enter TCA cycle via pyruvate carboxylation pathway and this activity was also found to be slightly decreased in the OAA treated cells. All the differences were statistically significant. These results indicate that OAA can be used to alter bioenergetics of GBM cells, specifically glucose oxidation.
Patient Age and Donor HLA Matching Can Stratify Allogeneic Hematopoietic Cell Transplantation (HCT) Patients into Prognostic Groups: A Collaborative Study
Authors: Sunu Cyriac, Auro Viswabandya, Zeyad Al-Shaibani, Jeffrey H. Lipton, Rajat Kumar, Wilson Lam, Dennis Dong Hwan Kim, Arjun Law, Tobias Gedde-Dahl, Yngvar Floisand, Mats Remberger, Jonas Mattsson, Fotios V. Michelis
Journal: Blood (2019)
Germline Gene Aberrations Are Common in High-Risk Adult and Pediatric Acute Lymphoblastic Leukemia Patients
Authors: Suvi Douglas, Atte Lahtinen, Jessica Koski, Lilli Leimi, Mikko A Keränen, Kimmo Porkka, Caroline A Heckman, Kirsi Jahnukainen, Outi Kilpivaara, Ulla Wartiovaara-Kautto
Journal: Blood (2019)
Mechanisms of Proteasome Inhibitor Resistance Selected By Clonal Evolution in Multiple Myeloma
Authors: Larissa Haertle, Santiago Barrio, Michal Simicek, Umair Munawar, Ricardo Sanchez, Max Bittrich, Matteo DaVia, Cornelia Vogt, Nicola Giesen, Andoni Garitano-Trojaola, Silvia Nerreter, Thorsten Stuehmer, Marc S. Raab, Joaquin Martinez Lopez, Roman Hajek, Hermann Einsele, Leo Rasche, Thomas Haaf, Martin Kortüm
Journal: Blood (2019)
ANGI-01. IDENTIFICATION OF INVASION-DETERMINISTIC TRANSCRIPTION FACTORS IN GLIOBLASTOMA USING INTEGRATIVE TRANSCRIPTOME ANALYSIS
Authors: Junseong Park, Jin-Kyoung Shim, Jae Eun Lee, Seon Jin Yoon, Jihwan Yoo, Ju Hyung Moon, Eui Hyun Kim, Jong Hee Chang, Seok-Gu Kang
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Although invasiveness is related to poor prognosis, no therapeutic intervention targeting invasion is available for treatment of GBM patient, partially due to the diversity and redundancy of invasion machinery genes. In this regard, additional identification of deterministic and causative targets for invasion is required. Invasiveness of GBM patients and matched tumorspheres (TSs) was quantified using MR images and collagen-based 3D invasion assays, respectively. Transcriptome of GBM samples were obtained using microarrays. The knockdown effects of invasion-deterministic transcription factors (TFs) were evaluated using western blot and mouse orthotopic xenograft model. This study is aimed to identify novel transcriptional regulatory networks, which can collectively modulate invasion-involved genes in GBM. After classification of 23 GBM patient-derived TSs into low and high invasion groups, we applied single sample gene set enrichment analysis using TF target gene sets. According to enrichment scores, TFs responsible for low (PCBP1) and high (STAT3 and SRF) invasiveness were identified. Consistently with computational prediction, knockdown of PCBP1 significantly increased invasion area, whereas knockdown of STAT3 or SRF significantly suppressed invasive properties in all tested TSs. Notably, MR images showed coherent patterns with invasion of originated TS, and high invasiveness was associated with poor prognosis. In addition, mouse orthotopic xenograft model using TSs with down-regulated STAT3 or SRF showed significantly prolonged survival time compared to control. We identified invasion-deterministic TFs in glioblastoma using integrative transcriptome analysis. Owing to relationship among these transcriptional regulatory networks, invasive phenotype, and prognosis, we suggest that these TFs as novel drug targets for GBM.
Translational and Clinical Evidence of a Differentiated Profile for the Novel CELMoD, Iberdomide (CC-220)
Authors: Sagar Lonial, Michael Amatangelo, Rakesh Popat, Monique C. Minnema, Jeffrey A. Zonder, Jeremy Larsen, Albert Oriol Rocafiguera, Erica L. Campagnaro, Paula Rodriguez Otero, Ashraf Z. Badros, David S. Siegel, Sundar Jagannath, Sara Bringhen, Mercedes Gironella, Martin F. Kaiser, Gordon Cook, Barbara Gamberi, Pieter Sonneveld, Tuong Vi Nguyen, Min S. Chen, Trevor Homan, Chad C. Bjorklund, Maria Wang, William E. Pierceall, Amine Bensmaine, Anjan Thakurta, Teresa Peluso, Niels W. C. J. Van De Donk
Journal: Blood (2019)
Whole Exome Sequencing of Relapsed Double-Mutated CEBPA Acute Myeloid Leukemia Identified Mutated KIT and WNT10A As a Potential Co-Mutation with Negative Impact on Prognosis
Authors: Chin-Hin NG, Alvin Yu-Jin Ng, Benedict Yan, Wee-Joo Chng
Journal: Blood (2019)