tbuckley/cabot-search huggingface dataset:
Protides of 5-Fluorotroxacitabine Display Potent Anti-Proliferative Properties and Circumvent Deoxycytidine Kinase-Mediated Resistance Associated with Cytotoxic Cytidine Analogues; A Novel Approach for Acute Myeloid Leukemia
Authors: Pedro Pinho, Helen Kylefjord, Vilma Rraklli, Christina Rydergård, Biljana Rizoska, Anders Eneroth, Johan Bylund, Sara Moses, Stefan Norin, Richard Bethell, Aniket Bankar, Thirushi Piyumika Siriwardena, Mark D. Minden, Aaron D Schimmer, Mark Albertella, Paul Targett-Adams
Journal: Blood (2018)
Erroneous data and drug industry bias can impair machine learning algorithms
Authors: Thomas Birk Kristiansen
Journal: BMJ (2019)

This important analysis focuses on the major obstacles that preventive precision medicine must overcome to fulfil its potential.1 Two further obstacles should be brought to attention.

First, erroneous data have great implications for machine learning algorithms used in predictive precision medicine. This holds true for historical data used to train algorithms and for new data used to make …
A quality improvement approach to optimizing infusion wait times.
Authors: Collin Plourde, Barbara Gleaton, Aliceson O'Hara, William Varnado, Devika Govind Das
Journal: Journal of Clinical Oncology (2019)

61 Background: Long wait times are a common and occasionally unavoidable experience for patients receiving chemotherapy infusions. It unfavorably impacts patient satisfaction and clinic efficiency. Our primary objective was to evaluate the impact of infusion clinic process changes on patient wait times within a Plan, Do, Study, Act (PSDA) framework. Methods: A multi-disciplinary team, consisting of oncology, nursing, pharmacy, quality improvement, and support staff, met to have brainstorming sessions, make surveys, and conduct time studies to analyze our current process (Plan). A Pareto chart created using survey results showed communication issues were likely causing the largest modifiable impact on our wait times. A common source of miscommunication was whether patients are waiting on labs results for treatment. Beginning March 2019, patients not requiring labs on the day of treatment were assigned to a separate scheduling title to designate them as priority for vital signs and review by pharmacy (Do). Upon clinic check-in, these patients now have vitals signs collected immediately and pharmacy is notified of their arrival to begin chemotherapy preparation. Results: Baseline as well as prospective wait time data was collected from 30 clinic days (360 patient wait times) from chart reviews and timestamp data available in the electronic medical record (EMR). Results were analyzed (Study) using Statistical Process Control (SPC) charts to allow for early detection of improvement. Pre-implementation wait times averaged 1 hour and 37 minutes. Post implementation wait times average 1 hour and 16 minutes (Act). This change was significant based on a shift visible on the SPC chart. Our balancing measure of wait times for all patients did not increase compared to baseline (2 hours and 15 minutes). No significant correlation was observed between average daily wait times and the day of the week or the number of patients treated that day at baseline. Conclusions: Implementation of a new clinic scheduling title and workflow reduced wait times for patients not requiring labs on the day of treatment without increasing wait times for patients requiring labs. Additional PDSA cycles will be conducted for further reductions in wait times for all patients at our site.
Abstract 940: Global Analysis of Histone Modifications and Long-range Chromatin Interactions Revealed the Differential Cistrome Changes and Novel Transcriptional Players in Dilated Cardiomyopathy
Authors: Chia-Feng Liu, Armen Abnousi, Peter Bazeley, Ying Ni, Michael Morley, Christine S Moravec, Ming Hu, WH Wilson Tang
Journal: Circulation Research (2019)

Background: Acetylation and methylation of histone alter the chromatin structure and accessibility that allows or prevents transcriptional regulators to bind to enhancers or promoters. The binding of transcriptional regulators enables the interaction between enhancers and promoters, thus affecting gene expression. However, our knowledge on the regulation of promoter and enhancer interactions and histone modifications in patients with heart failure remains limited. Methods and Results: We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) for major histone modifications and proximity ligation-assisted ChIP-seq (PLAC-seq) for long-range chromatin interaction for enhancer and promoter (E-P) using left ventricular tissues from dilated cardiomyopathy (DCM) patients and non-heart failure (NF) donors (n=2-3). We detected 37,531, and 8,587 differential H3K27ac and H3K4me3 regions between NF and DCM respectively (FDR &lt;0.05). While the average read density (ARD) for H3K27ac, an active enhancer histone mark, is similar between NF and DCM, we observed the ARD of H3K4me3, which marks the active promoter region of the genes, is significantly lower in DCM samples than in NF ones (p&lt;0.01). Super-enhancer (SE) analysis revealed that 481 and 119 genes are associated with NF- and DCM-specific SE respectively. Moreover, the differential E-P interactions were observed in the known heart failure gene loci, e.g., CTGF and NPPA-NPPB and these alternation interactions are correlated with the gene expression levels. Motif analysis identified known cardiac factors, such as MEF 2D and A and possible novel players, such as SOX transcription factors, namely SOX4 and SOX8, are enriched within enhancers and prompter regions identified in DCM samples. Their expression levels were confirmed with the whole-transcriptome analysis and protein assays. Conclusions: We have established cistrome for major histone modifications and long-range chromatin interaction for enhancer and promoter in NF and DCM tissues. The differential histone modifications and E-P interactions were found in DCM and these differences were associated with the gene expression level of a subset of disease-associated genes in human heart failure.
Mechanism of Tetrandrine in Combination with Droloxifen To Reverse Multidrug Resistance in Leukemia.
Authors: Bao-An Chen, Ai-ling Su, Feng Gao, Jian Cheng, Jia-Hua Ding, Chong Gao, Yun-yu Sun, Jun Wang, Gang Zhao, Ning-Na Chen, Hui-Hui Zhao, Xiao-Ping Pei
Journal: Blood (2007)
Primary non-adherence to adjuvant endocrine therapy in older women with breast cancer.
Authors: Vanina Tchuente, Donna Stern, Jaroslav Prchal, Judy Martin, Robyn Tamblyn, Ari N. Meguerditchian
Journal: Journal of Clinical Oncology (2019)

285 Background: Adjuvant endocrine therapy (AET) improves survival in hormone receptor positive breast cancer (HR+BC). Challenges with adherence to AET in seniors are well documented; however, there is limited knowledge on primary non-adherence (PNAD). PNAD is defined as non-initiation of a prescribed medication. Our aim is to characterize PNAD rates in women aged ≥ 65 with HR+BC and identify potential predictors, using real-time treatment information. Methods: Optimum is an e-health platform integrating real-time analysis of administrative claims data combined to patient-level clinical information on breast cancer. Optimum tracks care trajectories to identify deviations from best practice, using data from Quebec’s universal health insurance plan that covers all medical and pharmaceutical care. In this single-center feasibility study, we characterized PNAD as a non-initiation of AET within 10 days from the first prescription. Descriptive analyses were used to assess potential predictors. Results: Of the 57 patients enrolled, 9 were excluded due to lack of &gt; 30 day follow up. In the remaining 48 patients, PNAD was 21 %. Baseline Charlson comorbidity index (0 vs 13 %), psychotropic drug use (20 % vs 26 %) and polypharmacy rate (10 % vs 11 %) were lower in PNAD patients, compared to primary-adherent patients. PNAD patients had larger average tumor size (1.8 cm vs 1.6 cm), more often overexpressing HER2NEU (10 % vs 3 %), more negative progesterone receptor (10 % vs 5 %). They also more often had lumpectomy (70 % vs 65 %), SLNB (70 % vs 58 %) and more frequent margin revisions (30 % vs 16 %). They more often received chemotherapy (30 % vs 0 %). At 30-day follow-up, 40 % of PNAD patients had not yet initiated AET. Conclusions: This study confirms the feasibility of combining real-time administrative data and patient-level clinical information to assess breast cancer quality care. PNAD in women with HR+BC was higher than expected. PNAD patients had less comorbidities and drug use, but more aggressive cancers and more often also had quality challenges with surgical care (margin revision). PNAD predictors can potentially be used to identify patients that may require additional support to optimize disease management.
Bendamustine, Bortezomib and Dexamethasone (BVD): A Combination With a Substantial Activity and a Manageable Toxicity In Patients With Relapsed-Refractory Multiple Myeloma (MM)
Authors: Massimo Offidani, Laura Corvatta, Laura Maracci, Anna Marina Liberati, Stelvio Ballanti, Immacolata Attolico, Patrizia Caraffa, Francesco Alesiani, Tommaso Caravita di Toritto, Silvia Gentili, Patrizia Tosi, Marino Brunori, Daniele Derudas, Antonio Ledda, Alessandro Gozzetti, Claudia Cellini, Lara Malerba, Anna Mele, Alessandro Andriani, Sara Galimberti, Patrizia Mondello, Stefano Pulini, Ugo Coppetelli, Paolo Fraticelli, Attilio Olivieri, Pietro Leoni
Journal: Blood (2013)
Abstract 523: Myocardial Hypertrophy and Fibrosis Regulated by Nogo-ROCK-norepinephrine Transporter Signaling Pathway in Spontaneously Hypertensive Rats
Authors: Shijun Li
Journal: Circulation Research (2019)

Objective: To investigate the regulation of Nogo/ROCK- norepinephrine transporter (NET) signaling pathway on myocardial hypertrophy and fibrosis in spontaneously hypertensive rats (SHR). Methods: Twenty male SHR rats aged 7-week-old were randomly divided into four groups: control group (n=5), NEP1-40 group (n=5), fasudil group (n=5) and fluoxetine group (n=5), and fed for 7 weeks. Left ventricular mass (LVW) was separated and weighed. Left ventricular mass index (LVMI) was calculated. Real-time quantitative PCR was used to detect the gene expression of myocardial hypertrophy and fibrosis and NET. Results: Compared with the control group, the left ventricular mass index (LVMI), the gene expression of ANP, BNP andβ-MHC were significantly increased in NEP1-40 group, and were significantly decreased in Fasudil group. Compared with the control group, the gene expression of CTGF, Collagen I and Collagen III increased significantly in NEP1-40 group, while decreased significantly in Fasudil group. Compared with the control group, the gene expression of norepinephrine transporter (NET) significantly increased in fasudil group. Compared with the control group, the gene expression of ANP, BNP, β-MHC, CTGF and Collagen I were significantly increased in fluoxetine group. Conclusion: Nogo/ROCK-NET signaling pathway is involved in the regulation of myocardial hypertrophy and fibrosis in spontaneously hypertensive rats.
Association of Decreased Postsurgical Opioid Prescribing With Patients’ Satisfaction With Surgeons
Authors: Christopher E. Louie, Julia L. Kelly, Richard J. Barth
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Opioid overdose is the leading cause of injury-related death in the United States. Several studies have shown that surgeons overprescribe opioids, and guidelines for appropriate opioid prescribing are available. Concern about patient-reported satisfaction scores may be a barrier to surgeons adopting guideline-directed prescribing. <h3>Objective</h3> To determine whether decreased opioid prescribing is associated with a decrease in patient-reported satisfaction with their surgeon. <h3>Design, Setting, and Participants</h3> Retrospective analysis of clinician satisfaction scores at Dartmouth-Hitchcock Medical Center obtained in 2 periods: 1 before (period A) and 1 after (period B) an educational intervention that resulted in decreased opioid prescribing. The analysis included 11 surgeons who performed 5 common outpatient general surgical operations on 996 patients. Data were analyzed between March and August 2018. <h3>Main Outcomes and Measures</h3> Patient-reported overall satisfaction rating of the surgeon (scale, 0-10). This was collected by a nonstudy-related, routine general institutional survey of approximately 40% of all outpatient encounters. <h3>Results</h3> Of the total number of patients, 67% were women (667 of 996), and the mean patient age was 58 years. Comparing period A with B, the proportion of patients prescribed opioids decreased from 90.2% (n = 367 of 407) to 72.8% (n = 429 of 589) (<i>P</i> &lt; .001). The mean number of opioid pills per prescription decreased from 28.3 to 13.3 (<i>P</i> &lt; .001) and significantly decreased for each of the 11 surgeons. One hundred five of 996 patients (10.5%) undergoing index operations responded to the survey. There was no difference in the mean clinician satisfaction ratings from period A vs B (9.70 vs 9.65;<i>P</i> = .69). During the study periods, 640 total surveys were collected referencing these surgeons (including outpatient encounters associated with operations other than the 5 index cases). There was no difference in the mean satisfaction ratings from period A vs period B (9.55 vs 9.59;<i>P</i> = .62). When individual clinicians were analyzed, none had a significant difference in overall satisfaction rating from period A vs period B. <h3>Conclusions and Relevance</h3> Despite a marked decrease in the proportion of patients receiving opioids and in the number of pills prescribed, there was no significant change in clinician satisfaction ratings.
WT1 mRNA Expression in the Peripheral Blood of Patients with MDS Yields Additional Prognostic Information within the IPSS-R Risk Categories "Very Low", "Low" and "Intermediate"
Authors: Christina Rautenberg, Sabrina Pechtel, Norbert Gattermann, Rainer Haas, Ulrich Germing, Guido Kobbe, Thomas Michael Schroeder
Journal: Blood (2018)
The BCL-2-Selective Inhibitor Venetoclax Spares Activated T-Cells during Anti-Tumor Immunity
Authors: Rebecca Mathew, Dipica Haribhai, Fred Kohlhapp, Ryan Duggan, Paul Ellis, Jacob J Riehm, Valerie A Robinson, Yan Y Shi, Anahita Bhathena, Joel D. Leverson, William N Pappano, Cherrie K Donawho, Tamar Uziel
Journal: Blood (2018)
Efficacy and Safety of Daratumumab in a Frail Real-Life Relapsed or Refractory Systemic Light-Chain Amyloidosis Population (AL): Report on 15 Cases from the North of France
Authors: Zoe Van De Wyngaert, Benjamin Carpentier, Laurent Pascal, Pauline Lionne, Isabelle Leduc, Micha Srour, Michèle Vasseur, Hélène Demarquette, Charles Herbaux, Salomon Manier, Julia Hieulle, Jean-Baptiste Bossard, Sarah Barbieux, Paul Chauvet, Alexandre Willaume, Morgane Nudel, Arthur Simonnet, Claire Bories, Jean-Baptiste Gibier, Thierry Facon, Eileen M Boyle
Journal: Blood (2018)
New UK and US research alliance aims to detect cancer earlier and improve screening
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A new international alliance has launched with the aim of developing new strategies and technologies to detect cancer earlier and reduce overdiagnosis.

The International Alliance for Cancer Early Detection (ACED) is a partnership between Cancer Research UK, the Canary Center at Stanford University, the University of Cambridge, the OHSU Knight Cancer Institute, UCL, and the University of Manchester.

Its research will focus on a number of areas including improved imaging techniques to detect early tumours and precancerous lesions, and making screening more targeted and accurate to increase early diagnosis while reducing overdiagnosis and patient worry.

The alliance is hoping to accelerate progress by bringing together researchers, funding, and resources from these institutions, leading to quicker benefits for patients.

To fund the research, …
BRCA1/2 Containing Complex 3 (BRCC36) Is Recurrently Mutated in AML with t(8;21) and Associated with Increased Sensitivity to Chemotherapy through Impairment of the DNA Damage Repair Pathway
Authors: Tatjana Meyer, Nikolaus Jahn, Anna Dolnik, Peter Paschka, Verena I. Gaidzik, Daniela Weber, Lars Bullinger, Hartmut Döhner, Konstanze Döhner, Jan Kroenke
Journal: Blood (2018)
Mechanism of BAALC-Mediated Leukemogenesis Downstream of RUNX1-Mutations in Severe Congenital Neutropenia
Authors: Benjamin Dannenmann, Maksim Klimiankou, Benedikt Oswald, Malte U Ritter, Masoud Nasri, Anna Solovyeva, Lothar Kanz, Cornelia Zeidler, Karl Welte, Julia Skokowa
Journal: Blood (2018)
Abstract 272: Cardioprotective Effects of Plant-derived Fat in Low Carbohydrate Diet on the Progression of Heart Failure
Authors: Satoshi Bujo, Haruhiro Toko, Mutsuo Harada, Jiaxi Guo, Masato Ishizuka, Haruka Yanagisawa-Murakami, Issei Komuro
Journal: Circulation Research (2019)

Background: The association between low carbohydrate diet (LCD) and cardiovascular disease and mortality remains unknown. Results from meta-analyses have reported that cardiovascular mortality increased when the carbohydrate in LCD was replaced for animal-derived fat, whereas mortality decreased when the substitution was plant-derived fat. However, the molecular mechanism is yet to be elucidated. We aimed to assess the effects of the LCD under two conditions, LCD with animal-derived fat (LCD-A) and LCD with plant-derived fat (LCD-P), on mouse cardiac function. Methods: Using 10-week old male C57B/6J mice, we performed transverse aortic constriction surgery to generate a pressure overload model of heart failure and subjected them to either normal diet, LCD-A or LCD-P for 4 weeks. Cardiac function was measured by echocardiography at 4 weeks after surgery, and the extent of inflammation was assessed by immunohistological analysis. Expression levels of genes were assessed with RNA sequence. Results: LCD-A accelerated left ventricular dilatation and systolic dysfunction (P&lt;0.01 vs. normal diet), whereas LCD-P ameliorated cardiac hypertrophy (P&lt;0.01 vs. normal diet) as revealed by echocardiograpy. Immunohistological analysis demonstrated that LCD-A resulted in a significant increase in the infiltration of F4/80-positive macrophages, reflecting exacerbated inflammation (P&lt;0.01 vs. LCD-P, P&lt;0.01 vs. normal diet). Consistent with histological findings, inflammation-related and cell cycle-related gene expressions were upregulated only in LCD-A. On the other hand, mitochondrial fatty acid oxidation gene expression including PPARα targets such as Cpt1a, Slc25a20, Acadvl, Hadha and Acaa2 were upregulated only in LCD-P (P&lt;0.05, vs. normal diet), which may indicate the preserved energy metabolism during the pathogenic process of heart failure. Conclusions: These results suggest that the effects of the LCD on cardiac function vary between the sources of fat alternatives to carbohydrate intake. LCD-P induces PPARα activation, an important regulator of mitochondrial lipid metabolism, that may be therapeutically relevant for heart failure treatment. Further studies are required to unveil the precise molecular mechanism.
Improving Risk Assessment of AML with a Precision Genomic Strategy to Assess Mutation Clearance
Authors: Meagan Jacoby, David H Spencer, Emma Hughes, Robert S Fulton, Michelle O'Laughlin, Catrina Fronick, Michael R. Loken, Jack D Baty, Mark A. Schroeder, Armin Ghobadi, Geoffrey L. Uy, Ravi Vij, Brad S Kahl, Amanda F Cashen, Matthew J. Walter, Lukas D Wartman, John S. Welch, John F. DiPersio, Peter Westervelt, Timothy J Ley
Journal: Blood (2018)
The Effect of Hemoglobin (Hb) Level at ESA Initiation on Outcomes in Cancer Patients (pts) with Chemotherapy-Induced Anemia (CIA): A Patient-Based Meta-Analysis from 6 Randomized, Placebo-Controlled Trials (RCTs) of Darbepoetin alfa (DA).
Authors: J. Crawford, D. Henry, J. Vansteenkiste, H. Ludwig, T. Lillie, A. Fleishman, J. Glaspy
Journal: Blood (2007)
Comprehensive Analysis of Chemokines in Host Organs and Their Corresponding Receptors on Donor T-Cells in Xenogeneic Gvhd Model
Authors: Yasufumi Kawasaki, Kazuya Sato, Hirofumi Nakano, Kiyomi Mashima, Daisuke Minakata, Ryoko Yamasaki, Kaoru Morita, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Shin-ichiro Fujiwara, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
Journal: Blood (2018)
Randomized Comparison of IV PEG and IM E. Coli Asparaginase in Children and Adolescents with Acute Lymphoblastic Leukemia: Results of the DFCI ALL Consortium Protocol 05-01
Authors: Lewis B. Silverman, Kristen Stevenson, Lynda M Vrooman, Jeffrey G Supko, Barbara Asselin, Uma Athale, Luis A. Clavell, Peter Cole, Kara M Kelly, Caroline Laverdiere, Bruno Michon, Marshall A. Schorin, Cindy Schwartz, Donna Neuberg, Stephen E. Sallan
Journal: Blood (2011)
Autophagy in Myelodysplastic Syndromes: The Role of HIF-1a/REDD1 Molecular Pathway
Authors: Ioanna Stergiou, Konstantinos Kambas, Stavroula Giannouli, Theodora Katsila, Aglaia Dimitrakopoulou, Veroniki Vidali, Evgenia Synolaki, Aristea Papageorgiou, Andrianos Nezos, George Patrinos, Paschalis Sideras, Konstantinos Ritis, George Vassilopoulos, Athanasios Tzioufas, Michael Voulgarelis
Journal: Blood (2018)
SMALL Molecules Mediated Hematopoietic STEM and Progenitor CELLS Expansion for GENE Editing Application
Authors: Abisha Crystal C, Saravanabhavan Thangavel, Shaji Ramachandran Velayudhan, Alok Srivastava, Aneesha Nath, Saranya Srinivasan, Vigneshwaran Venkatesan
Journal: Blood (2018)
Migrant health: Trusts asked GPs to identify whether patients they refer are eligible for free NHS care
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Hospital managers who are responsible for charging overseas patients for NHS treatment asked some general practices to help them identify whether patients were eligible for free care, the BMA has said.1

The BMA’s General Practitioners Committee warned GPs in a newsletter that overseas visitor managers had written to some London practices and asked them to note on referral letters those patients who were regarded as “overseas visitors” because they had been a UK resident for less than six months.

Both the GPC and Londonwide Local Medical Committees have told GPs that this was not their responsibility, as set out …