tbuckley/cabot-search huggingface dataset:
Developing clinical indicators to effectively monitor a large network of radiation oncology practices.
Authors: Seth D. Frey, Karen E. Hoffman, Anuja Jhingran, Mary Frances McAleer, Bruce D. Minsky, Steve Kirsner, Gurpreet Arora, Denise Zaebst, Ivy Robinson, Terence Roberts, Ashish Bharat Patel, Michael Ray Olson, Molly Gabel, Yasemin Bolukbasi, Manolo Llorente, Icaro Thiago de Carvalho, Robert Ghafar, Albert Koong, Joseph M. Herman, Deborah A. Kuban
Journal: Journal of Clinical Oncology (2019)

236 Background: The MD Anderson Cancer Network includes 29 distinct Radiation Oncology facilities spread across metropolitan Houston area locations, national partnerships, and international affiliates. Standard performance indicators (PIs) were developed to monitor the quality and safety of radiation treatment at these facilities spread across the globe. Methods: Stakeholders from Radiation Oncology nursing, dosimetry, physics, radiation therapy, and clinical operations identified PIs that measure safe, efficient, and effective radiation oncology care. PIs are collected monthly from each facility and are reported in a scorecard that includes performance goals. The appropriateness and effectiveness of the PIs are reviewed annually to determine if PIs need to be added, removed, or revised. Results: As the network expanded, scorecard use expanded from 11 facilities in 2013 to 29 facilities in 2019. Select PIs are summarized in the table. Scorecard composition has evolved over time. PIs such as completion of simulation orders and treatment planning directives were removed once consistently reaching 100% after improved monitoring, process improvements, and implementation of hard stops. The scorecard has been especially useful when onboarding new facilities, as evidenced by PIs increasingly meeting performance thresholds in the first year after joining the network. For example, one facility increased PI compliance from 61% to 100% the first year after joining the network. Conclusions: It is feasible to develop and implement a performance indicator scorecard across a large radiation oncology network. The scorecard permits timely assessment of quality indicators, provides oversight, and is effective in stabilizing operations at newly on-boarded radiation oncology practices. [Table: see text]
C3aR1 Contributed to Acute Myeloid Leukemia Acquired Resistance to ABT-737 and Involved In the Process of AML
Authors: Shaoyan Hu, Saied Mirshahidi, Chong-Lei Bi, Wee-Joo Chng, Heng-Wei Hsu, Shui-yan Wu, Jian Pan, Jian-nong Cen, Chien-Shing Chen
Journal: Blood (2011)
Urgent treatment must never be withheld from migrants
Authors: Lauren Z Waterman
Journal: BMJ (2019)

Dyer reports on the devastating case of Kelemua Mulat, a 39 year old asylum seeker who died after delays to her cancer treatment amid confusion over whether she was eligible for free NHS care.1 Regardless of whether migrants in England are deemed eligible for free NHS care, they are exempt from upfront charging for all NHS services …
Changing Patterns, and Clinical Correlates, of Mutations in Patients with Myelofibrosis over Treatment with Ruxolitinib or Hydroxyurea
Authors: Alessandro M. Vannucchi, Annalisa Pacilli, Giada Rotunno, Francesco Mannelli, Chiara Paoli, Carmela Mannarelli, Annalisa Franci, Tiziana Fanelli, Alessandro Pancrazzi, Francesca Gesullo, Giuditta Corbizi Fattori, Alberto Bosi, Paola Guglielmelli
Journal: Blood (2017)
A nutrition-focused quality improvement program to improve rate of documented nutrition plan at a safety-net hospital gastrointestinal (GI) oncology clinic.
Authors: Nicholas Levonyak, Mary P Hodges, Nicole Broome, Muhammad Shaalan Beg, Radhika Kainthla, Aravind Sanjeevaiah, Navid Sadeghi, Neha Pandey, Verca Mhoon, John Vernon Cox, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2019)

289 Background: Patients with GI cancer have amongst the highest rates of malnutrition, which contributes to decreased quality of life, increased morbidity and mortality, as well as higher healthcare costs. In the GI Oncology clinic at Parkland Health and Hospital System (PHHS), the number of patients with a documented nutritional plan by a registered dietitian was 7%, and there was no standardized screening method for malnutrition in place. Methods: The aim was to increase the rate of documented nutritional assessment by a registered dietitian to 25%. Multidisciplinary sessions involving physicians, registered dietitians, registered nurses, and hospital administration were arranged to identify barriers to nutritional interventions for GI Oncology clinic patients. Results: Prior to QI interventions, between October-December 2018, the total number of GI cancer patients referred to registered dietitian clinic was 11- 30 referrals, which accounted for 7-10.1% of GI cancer patient in the respective month. As part of first PDSA cycle, a registered-dietitian was assigned to GI oncology clinic. The total number of documented nutrition plan after first intervention was 22 GI cancer patient (15% of GI cancer patients). We then developed an adapted-version of the Malnutrition Screening Tool (MST) and implemented it through the institute electronic medical record. The nursing staff and physicians were educated about administering the screening tool and the referral process to a registered-dietitian after a positive MST screen. After the first month during which MST was implemented, the rate of nutritional assessment increased to total of 20.5% of GI cancer patients (total 37 referrals). Twenty out of the 37 referrals (54%) were due to the positive MST screening tool. Conclusions: Through a nutrition focused QI program, we doubled the rate of a documented nutritional plan for PHHS GI cancer patients in a month of starting the 2nd PDSA cycle intervention. Through future PDSA cycles, we plan to further increase patient access to nutritional assessments and then broaden our efforts to the entire PHHS oncology clinic.
Abstract 412: Wnt / β-catenin Inhibitor Differentiates Human Mesenchymal Stem Cells into Myogenic Lineage <i>in vitro</i> and Improved Cardiac Function <i>in vivo</i> in Rat Model of Myocardial Infarction
Authors: Irfan Khan, Syeda R Ali, Asmat Salim
Journal: Circulation Research (2019)

Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality. At present, available therapeutic options for the treatment of cardiovascular diseases are limited and provide solution only to reduce the symptoms of CVD. The indigenous capability of cardiac tissue to meet the degeneration is limited. The feasible option is stem cells based regenerative medicine to repair or regenerate the myocardial cells and restore normal cardiac function. The aim of the present study is to assess the potential of small molecules for the differentiation of MSCs into cardiomyocytes. In this study, MSCs were cultured in vitro and were characterized by immunochemistry, and flow cytometry for the presence of MSCs markers, CD90, CD73, CD44, CD29, and for tri-lineage differentiation. MSCs were treated with wiki-4 for 14 days to induce cardiac differentiation, and were characterized for the presence cardiac markers by gene and protein expression for GATA-4, α-actinin, cTnT, cTnI, and myosin heavy chain, and found positive for these markers. These induced cardiac progenitor cells were transplanted into the infarcted myocardium of rats, where they exhibited increased persistence, engraftment, and homing in the infarcted region, and expressed cardiac markers within the border zone. Transplanted group improved left ventricular wall thickness at 4 weeks post injury, and reduced infarct size. Functional performance of the hearts was analyzed through M-mode echocardiography, which results in significant (p&lt;0.05) improvement in the heart function including left ventricular internal diameter systolic and diastolic, ejection fraction, fractional shortening, end systolic volume and diastolic volume, and stroke volume compared to control. Histological examination of the heart sections 4 weeks post MI showed that MSCs home towards the site of injury. The transplanted cells expressed cardiac markers and contributed to the cardiac tissue recovery. The results of the present study demonstrate that myocytes derived of MSCs enhance the regeneration potential of the infarcted myocardium.
Guiding Therapy by Coronary CT Angiography Improves Outcomes in Patients With Stable Chest Pain
Authors: Philip D. Adamson, Michelle C. Williams, Marc R. Dweck, Nicholas L. Mills, Nicholas A. Boon, Marwa Daghem, Rong Bing, Alastair J. Moss, Kenneth Mangion, Marcus Flather, John Forbes, Amanda Hunter, John Norrie, Anoop S.V. Shah, Adam D. Timmis, Edwin J.R. van Beek, Amir A. Ahmadi, Jonathon Leipsic, Jagat Narula, David E. Newby, Giles Roditi, David A. McAllister, Colin Berry
Journal: Journal of the American College of Cardiology (2019)

Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint). This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint. In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies. Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size. The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)
Abstract 134: Direct Reprogramming of Fibroblasts into a Cardiovascular Tissue
Authors: Jaeyeaon Cho, Sangsung Kim, Young-sup Yoon
Journal: Circulation Research (2019)

Background: Direct reprogramming of fibroblasts into cardiomyocytes (CMs), endothelial cells (ECs), or smooth muscle cells (SMCs) has emerged as a promising strategy for cell-based therapy. Moreover, tissue engineering has become a crucial means to enhance the effects of the cell therapy. However, simultaneous reprogramming of somatic cells into all three cell types or a tissue-like structure has not been investigated despite its significance. Here, we aimed to directly reprogram fibroblasts into a cardiovascular tissue containing all three cell types and determined their regenerative effects on infarcted hearts. Methods and results: Adult mouse fibroblasts were transfected with a pre-selected cardiac microRNA mimic, miR-208b-3p, and treated with ascorbic acid and BMP4 one day after the transfection for 9 days. At day 10, cells were reprogrammed into a tissue-like structure referred to as reprogrammed cardiovascular tissue (rCVT), which contains reprogrammed CM (16.9 ± 8.0% positive for TNNT2)-, EC (28.4 ± 3.5% positive for PECAM1)-, and SMC (12.0 ± 2.9% positive for SMTN)-like cells, and 14 identified mouse proteins of extracellular matrix. Sarcomeric striations, calcium oscillations and action potentials were shown in reprogrammed CMs. Reprogrammed ECs took up Dil-conjugated acetylated low density lipoprotein and reacted with DAF-FM diacetate, suggesting production of nitric oxide by the cells. Therapeutic effects of rCVT were determined on a mouse model of myocardial infarction with echocardiography and histological analysis over 4 months. Implantation of this rCVT onto the infarcted mouse heart reduced regional cardiac strains and improved cardiac function. Histological examination showed migration of reprogrammed cells from rCVT into the infarcted hearts. Migrated rECs and rSMCs contributed to vessel formation in collaboration with host vascular cells. Migrated rCMs initially displayed immature characteristics but became mature over time and formed gap junctions with host CMs. Conclusions: This study demonstrates that a combination of miR-208b-3p, AA and BMP4 can directly reprogrammed single adult somatic cells into a cardiac tissue-like structure containing CMs, ECs, and SMCs, and that rCVT is effective for cardiac repair.
The mTOR Inhibitor Rapamycin Inhibits Drug Transport in Multidrug Resistant Cell Lines and in Acute Myeloid Leukemia (AML) Cells.
Authors: Attaphol Pawarode, Kieran L. O’Loughlin, Nicholas W. Cuviello, William R. Greco, Laurie A. Ford, Hans Minderman, Maria R. Baer
Journal: Blood (2005)
Development of a Novel Class of Agents Targeting the RNA-Splicing Machinery in Myeloid Malignancies
Authors: Valeria Visconte, Bartlomiej P. Przychodzen, Vera Adema, Cassandra M. Hirsch, Allison Noe, Rachel Toth, Christina Snider, Hassan Awada, Amy C Graham, Yvonne Parker, Yuriy Fedorov, Drew Adams, Hetty E. Carraway, Anjali S. Advani, Tomas Radivoyevitch, Heesun J. Rogers, Kevin R Kelly, Steffan T. Nawrocki, Jennifer S. Carew, Daniel Lindner, Richard A Padgett, Mikkael A. Sekeres, James G Phillips, Jaroslaw P. Maciejewski
Journal: Blood (2018)
Neutrophil Extracellular Traps Induced By Activated Platelets Contribute to Hypercoagulable State in Patients with Colorectal Cancer
Authors: Yan Zhang, Baorong Li, Yingmiao Liu, Cong Zhang, Yan Kou, Lili Zou, Hui Liang, Li Hou, Tao Li, Muxin Yu, Chunxu Wang, Jingwen Du, Yueyue Li, Haijiao Jing, Jin Zhou, Jialan Shi
Journal: Blood (2018)
Evaluation of the BD Phoenix™ CPO Detect Test for the detection of carbapenemase producers
Authors: A. Croxatto, A.T. Coste, T. Pillonel, C. Bertelli, G. Greub, G. Prod'hom
Journal: Clinical Microbiology and Infection (2019)

ObjectivesBecton-Dickinson recently developed the Phoenix™ CPO (carbapenemase-producing organism) Detect Test, a growth-based test embedded in Gram-negative (GN) panels for the detection and confirmation of bacteria producing class A, B and D carbapenemases. This study aimed to (a) determine the performance of the CPO test, and (b) assess its added value in routine diagnostic workflows.MethodsThe performance of the BD Phoenix CPO test was analysed retrospectively on a collection of 185 molecularly characterized strains, including 92 CPOs, and prospectively on 135 and 160 routine isolates with and without CPO suspicion, respectively.ResultsIn the retrospective study the CPO test exhibited 92.4% accuracy (95%CI 87.6–95.8), 97.8% sensitivity (95%CI 92.4–99.7) and 87.1% specificity (95%CI 78.6–93.2) for carbapenemase detection. The CPO test provided a classification to class A, B, and D for 81.3% of detected carbapenemases with 94.6% accuracy (95%CI 86.7–98.5). In the prospective study the CPO test detection performance showed 77.8% accuracy (95%CI 68.8–84.5), 100% sensitivity (95%CI 91.2–100) and 67.8% specificity (95%CI 57.3–77.1) with 135 CPO-suspicious isolates and 98.8% accuracy and specificity (95%CI 95.6–99.9) with 160 non-CPO-suspicious isolates. Compared to routine testing, the implementation of the CPO test allowed a mean reduction of 21.3 h (95%CI 17.6–25) in turnaround time, 16.8 min (95%CI 13.4–20.2) in hands-on time, and 20.6 CHF (95%CI 16.5–24.8) in costs.ConclusionsThe CPO test is reliable for the detection of CPO with a high sensitivity. However, the relatively low detection specificity required the use of additional confirmatory methods. The carbapenemase classification accuracy is robust in providing preliminary results before molecular characterization. Finally, the implementation of the test in routine workflows allowed a significant reduction in turnaround time, hands-on time and cost compared to the conventional approach.
The Role of Shelterin Complex and Post-Translational Non-Enzymatic Modification in Telomere Maintenance in Chronic Myeloid Leukemia
Authors: Anna Deregowska, Katarzyna Pruszczyk, Iwona Solarska, Ilona Seferynska, Marek Dudzinski, Maciej Wnuk, Tomasz Stoklosa
Journal: Blood (2018)
Treatment for X-Linked Agammaglobulinemia with Allogeneic Umbilical Cord Blood Stem Cell Transplantation from HLA-Matched Sibling Confirmed Healthy through Prenatal Diagnosis
Authors: Dingming Wan, Ran Zhang, Meng Wang, Li Li, Weijie Cao, Suping Zhang, Kai Sun, Xiaona Chen, Na Zhang
Journal: Blood (2018)
Studying Methylation Status of Protein Tyrosine Phosphatase Receptor Gamma (PTPRG) in Chronic Myeloid Leukemia Patients in the State of Qatar
Authors: Mohamed Ismail, Marzia Vezzalini, Ali Al Sayab, Maria Monne, Vinod Gupta, Govundarajulu Varadharaj, Mohamed Alsharshani, Mohamed Yassin, Claudio Sorio, Helmout Modjtahedi, Nader I. Al-Dewik
Journal: Blood (2018)
Abstract 860: Functional Characterization of a Novel Human Heart-specific Microprotein With a Potential Mitochondrial Localization and Role in Sarcomere Dynamics
Authors: Michael Benedikt B Muecke, Jana F Schulz, Valentin Schneider, Arun Sharma, Christopher N Toepfer, Sebastiaan van Heesch, Jonathan G Seidman, Christine E Seidman, Norbert Hübner
Journal: Circulation Research (2019)

Cardiac microproteins are an emerging class of important regulators of cellular homeostasis, often encoded by presumed long noncoding RNAs. With only few described so far, their prevalence and biological significance largely remains unclear. To create an atlas of cardiac-expressed microproteins, we performed ribosome profiling on 80 human heart samples. This revealed the translation of hundreds of previously undetected microproteins, which we validated in vivo by targeted mass spectrometry. A single heart-specific microprotein caught our attention as it showed strong expression coregulation with components of mitochondrial OXPHOS pathway. We next deleted this microprotein's lncRNA host gene in hiPSCs using CRISPR/Cas9, and, upon differentiation into 30-d old cardiomyocytes, find a strong expression upregulation of genes involved in oxidative phosphorylation and calcium handling. To investigate the impact of the microprotein KO on cardiomyocyte mechanical function, we assessed sarcomere dynamics using an endogenous TTN-GFP tag, enabling live cell imaging analysis with the SarcTrack algorithm. Preliminary analysis sowes a putative increase in sarcomere contraction and relaxation times, suggesting a repressive regulatory function of the eliminated microprotein encoding lncRNA.
Possible Biomarkers To Predict Response In Patients With Myelodysplastic Syndromes (MDS) Or Acute Myeloid Leukemia (AML) Treated With 5-Azacitidine
Authors: Andrea Kuendgen, Catharina Müller-Thomas, Petra Urbaniak, Michael Lauseker, Torsten Haferlach, Tamara Alpermann, Andreia Albuquerque, Alexander Kohlmann, Susanne Schnittger, Barbara Hildebrandt, Brigitte Royer-Pokora, Norbert Gattermann, Rainer Haas, Ulrich Germing, Katharina Götze
Journal: Blood (2013)
Five-Year Follow-up of Safety and Efficacy of a Phase III Randomized Trial of Ofatumumab Therapy Versus Physicians' Choice in Patients with Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia
Authors: Udvardy Miklos, Vladimir Strugov, Catharina Lewerin, Sebastian Grosicki, Grzegorz Mazur, Michael Steurer, Marco Montillo, Irina Kryachok, Jan Moritz Middeke, Grygoriy Rekhtman, Tommaso Stefanelli, Ghislaine Vincent, Sameera G, Anders Österborg
Journal: Blood (2018)
Comparing health utility scores, treatments, and outcomes in lung cancer patients with rare EGFR mutations with those with exon 19 deletion (del) and L858R mutations.
Authors: Lorin Dodbiba, Katrina Hueniken, Shirley Xue Jiang, Sze Wah Samuel Chan, Elliot Charles Smith, Lawson Eng, Devalben Patel, Maryam Razooqi, M. Catherine Brown, Frances A. Shepherd, Natasha B. Leighl, Penelope Ann Bradbury, Wei Xu, Adrian G. Sacher, Geoffrey Liu
Journal: Journal of Clinical Oncology (2019)

102 Background: Precision oncology divides patients into smaller cohorts each with unique characteristics, treatment and outcomes. Cost-effectiveness assessments that rely on quality-adjusted life years will require mutation-specific health utility scores (HUS). We assessed the impact of having exon 19 del, L858R and rare EGFR mutations on outcomes and HUS. Methods: From a retrospective database of 719 patients with EGFR mutations, specific baseline EGFR mutations, clinicodemographic and treatment characteristics, and outcomes (overall survival, OS; progression-free survival, PFS) were analyzed using Cox models (adjusted hazard ratios, HR). In a subset of 289 patients with metastatic disease, serial HUS data collected through EQ-5D-5L at clinic visits were compared by mutation using t-tests. Results: Of 380 (53%) patients with exon 19 del, 288 (40%) with L858R, and 51 (7%) with rare mutations (mostly G719A/C, Exon 18 or 20 insertion, L861Q, compound mutations): 68% were female; median age was 74 years; 51% were Asian; and 74% were never smokers. In 334 Stage I-III pts, recurrence-free survival was not associated with specific mutations. In contrast, among 365 stage IV pts on TKIs, when compared to a reference of patients with exon 19 del, outcomes were worse in patients with L858R mutations (PFS: 1.35, 95% CI 1.1-1.7; OS: HR 1.39, 95% CI 1.0-1.9) and for rare mutations (PFS: 1.16 95% CI 0.7-1.9; OS: 1.45 95% CI 0.7-2.9). From an analysis of 1064 clinic encounters, different TKIs were used in similar proportions by mutation. In stable disease, mean HUS [SEM] were 0.80 [0.008] (exon 19), 0.81 [0.009] (L858R), and 0.82 [0.02] (rare mutation). Progressive disease led to significant drops in mean HUS for exon 19 (0.76 [0.01]; p = 0.01 compared to stable disease) and L858R, mean HUS = 0.74 [0.02] p &lt; 0.001, but less so for rare mutations, mean HUS = 0.79 [0.05] p = 0.65. Conclusions: Patients in this EGFR mutated cohort had similar exposures of different TKI therapy regardless of specific EGFR mutation. L858R and rare mutations had inferior survival outcomes but similar HUS as patients with exon 19 del mutations.
Long-Term Follow-up of Patients Affected by Relapsed Lymphomas Receiving Reduced-Intensity Conditioning (RIC) Regimen Followed by Allogeneic Stem Cell Transplantation (Allo-SCT): An Update of the Phase II Study of the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO)
Authors: Paolo Corradini, Anna Dodero, Lucia Farina, Roberto Fanin, Francesca Patriarca, Rosalba Miceli, Paola Matteucci, Fabio Ciceri, Rosanna Scime’, Franco Narni, Enrico Pogliani, Anna Locasciulli, Serena Dalto, Cristiana Carniti, Andrea Bacigalupo, Alessandro Rambaldi, Francesca Bonifazi, Attilio Olivieri, Mats L Brune, Alessandro M. Gianni, Corrado Tarella
Journal: Blood (2008)