tbuckley/cabot-search huggingface dataset:
Abstract P031: Effect of Exercise on Function and Differentiation of Adipose Tissue Derived Mesenchymal Stromal Cells (MSCs)
Authors: Nabanita Kundu, Cleyton Domingues, Peter Kokkinos, Eric Nylen, Sabyasachi Sen
Journal: Circulation (2018)

Approximately 422 million people have diabetes worldwide (2014) and it is predicted that diabetes will rise by nearly 54% by 2030. Aerobic exercise is known to show positive effect on health of diabetic and pre diabetic patients. The effect of exercise has been studied extensively using plasma biochemistry but cellular data is scares. Previously, we have shown endothelial progenitor cells (EPCs) can act as a strong cellular biomarker of endothelial function following aerobic exercise as an intervention. In this study, we are examining the effect of aerobic exercise on adipocyte derived MSCs to study stromal cell differentiation and as a cellular surrogate of fat metabolism. Methods: Overweight and obese subjects (n=5) were enrolled in a 12 week exercise intervention study. The biweekly exercise sessions were supervised by a trained exercise physiologist and consisted of a 1 hour sessions that included warm-up and cool-down and 30 min of combined aerobic and resistance training at an exercise intensity of 50-80% of heart rate reserve. Physical and biochemical parameters were tested pre and post exercise. Subcutaneous abdominal fat biopsies were obtained and fat derived stromal cells were cultured in vitro for 2-3 weeks. MSCs were analyzed for mRNA gene expression (qRT-PCR) and cellular oxygen consumption rate (OCR), pre and post 12 week exercise. Results: With exercise, A1C reduced significantly. An increase of METs was also noticed post exercise. Both basal and maximal respiration increased significantly post exercise when compared with commercially obtained MSCs. Simultaneously, mitochondrial genes COX4 and ATP5B (p= 0.01, 1.4 fold, 0.02, 1.5 fold respectively), Glucose transporter, GLUT1 (p=0.04, 1.8 fold), antioxidants GPX3 and CAT (p= 0.01, 3.2 fold and p=0.04, 1.5 fold respectively) upregulated whereas pro-inflammatory cyclo-oxygenase-2 (p=0.04, 2.5 fold) gene reduced significantly, post exercise. Regarding differentiation potential of multipotent MSCs, post exercise, we noted enhanced expression of bone markers such Alkaline Phosphatase (p= 0.03, 2.7 fold) BGLAP and RUNX2 (1.3 and 1.2 fold) and also for collagen marker COL2 (2.4 fold) expression. For adipogenic differentiation potential PPARG mRNA expression was reduced. Interestingly, serum value of osteocalcin increased significantly from 15.0 (5.5) to 16.3(6.1) ng/ml (9% increase, p=0.03) with 1% increase in bone alkaline phosphatase level, post exercise. Conclusion: We conclude that exercise augments cellular glucose transporters (GLUT1), anti-oxidants and reduce MSC inflammation and up-regulates mitochondrial function and gene expression profile of MSCs. Increased serum value of osteocalcin complement increased gene expression of bone formation markers indicating a cross talk between fat derived MSCs and bone formation, post exercise.
Immunophenotypic Characteristics of Olygomonocytic Chronic Myelomonocytic Leukemia Support Its Diagnosis As a Distinctive Entity in the Continuum of Chronic Myelomonocytic Leukemia
Authors: Xavier Calvo, Ivonne Parraga, Lourdes Florensa, Sara Montesdeoca Romero, Anna Puiggros, Marta Salido, Blanca Espinet, Anna Angona, Ana Ferrer, Carme Pedro, Leonor Arenillas
Journal: Blood (2018)
Differential Effects of TCR Stimulation and IL-2 On Apoptotic Pathways in CD4 Regulatory T Cells Compared to Conventional CD4 T Cells and CD8 T Cells
Authors: Kazuyuki Murase, Yutaka Kawano, Jeremy Ryan, Ken-ichi Matsuoka, Gregory Bascug, Sean McDonough, Robert W Smith, Suzan Lazo-Kallanian, John Daley, Matthew S. Davids, Anthony G. Letai, Jerome Ritz
Journal: Blood (2012)
Abstract 418: Ready-made Microvessels Robustly Integrate Into the Infarcted Coronary Vasculature Promoting Graft Perfusion, Enhancing Cardiac Remuscularization and Function
Authors: Sara Nunes Vasconcelos, Xuetao Sun, Jun Wu, Ren-Ke Li
Journal: Circulation Research (2019)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted hearts. However, the majority of hiPSC-CMs die post transplantation into the ischemic environment, limiting their regenerative potential. CM death occurs in the first few days post-transplantation due to ischemia. Attempts to promote intramyocardial vascularization (i.e. delivery of growth factors or cells) have not led to significant improvements due to poor cell retention and the long time required for new vessels to form and carry blood compared to the rapid death of transplanted CMs. Here, we used ready-made microvessels harvested from adipose tissue - that form a vasculature and carry blood within the first days post subcutaneous implantation - to re-vascularize ischemic rat hearts and improve hiPSC-CM survival. We performed left anterior descending artery ligation in immunocompromised rats to model MI. hiPSC-CMs (10 x10 6 ) with (CM+V) or without (CM-only, control) microvessels were delivered by intra-myocardial injection 2 weeks post MI. Cardiac function was assessed by echocardiography and pressure-volume loop. Delivery of microvessels from GFP rats allowed assessment of microvessel persistence. Compared to hiPSC-CM transplantation alone, microvessels promoted a 6-fold increase in hiPSC-CM survival, with reduction in scar size and a significantly superior functional recovery. While delivery of CM-only stabilized the heart preventing further fractional shortening decline, delivery of CM+V resulted in reversal of fractional shortening loss. This was supported by PV-loop data (ejection fraction: sham, ~20%; CM-only, ~31%; CM+V, ~39%; 4 wks). Moreover, microvessels showed unprecedented persistence and integration (&gt;60%, 4 wks), resulting in 2-fold increase in vessel area and graft perfusion (as early as day 5 post-transplantation). This was achieved despite the very low number of cells (~2 x10 5 ) delivered in the form of microvessels. These findings provide a novel approach to cell-based therapies for MI whereby incorporation of ready-made microvessels can serve as a personalized delivery system to improve functional outcomes in cell replacement therapies.
Characterization of Platelet Activation in Patients with Eisenmenger Syndrome
Authors: Gordon Haire, Karl Egan, Barry Kevane, Michael Fay, Anne Fortune, Rhona Savage, Esther Doran, Ciara O'Neill, Kevin Walsh, Damien Kenny, Aine Lennon, Patricia Maguire, Fionnuala Ni Ainle
Journal: Blood (2018)
Mutational and Clonal Landscape of Acute Myeloid Leukemia with Myelodysplastic Related Changes
Authors: Guillermo Montalban Bravo, Rashmi Kanagal-Shamanna, Christopher B. Benton, Simona Colla, Irene Ganan-Gomez, Koji Sasaki, Farhad Ravandi, Tapan M. Kadia, Jorge E. Cortes, Naval G. Daver, Koichi Takahashi, Courtney D. DiNardo, Elias J. Jabbour, Gautam Borthakur, Kiran Naqvi, Marina Y. Konopleva, Sherry A. Pierce, Carlos E. Bueso-Ramos, Keyur Patel, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2018)
Spectrum of Gene Mutations and Clinical Significance in Myeloid Malignancies Patients with ASXL1 Mutations
Authors: Jie Bai, Guangshuai Teng, Yingshao Wang, Jing Xu, Chenxiao Du, Yan Wang, Yafang Chen, Mengyao Sheng, Jiaojiao Bai, Lei Zhang, Yuan Zhou, Feng-Chun Yang
Journal: Blood (2018)
Successful Treatment with Bortezomib in Combination with Bendamustine and Prednisone of Patients with Newly Diagnosed/Untreated Multiple Myeloma and Light Chain Induced Renal Failure
Authors: Wolfram Pönisch, Marc Andrea, Ina Wagner, Doreen Hammerschmidt, Ute Kreibich, Andreas Schwarzer, Thomas Zehrfeld, Maik Schwarz, Cornelia Winkelmann, Sirak Petros, Anette Bachmann, Tom Lindner, Dietger Niederwieser
Journal: Blood (2011)
Measuring financial toxicity of cancer in the Italian health care system: Initial results of the patient reported outcome for fighting financial toxicity of cancer project (proFFiT).
Authors: Jane Bryce, Silvia Riva, Massimo Di Maio, Fabio Efficace, Luciano Frontini, Ciro Gallo, Diana Giannarelli, Vincenzo Montesarchio, Francesco De Lorenzo, Laura Del Campo, Elisabetta Iannelli, Francesca Traclò, Lara Gitto, Claudio Jommi, Concetta Maria Vaccaro, Anna Gimigliano, Lucia Sparavigna, Francesco Perrone
Journal: Journal of Clinical Oncology (2019)

91 Background: Financial toxicity in cancer patients has been initially reported in the United States and subsequently in other countries, including Italy, despite its health care system is grounded on universal coverage. Considering that the way healthcare and welfare systems are shaped does impact on financial problems faced by cancer patients, we are developing an instrument for evaluating occurrence, gravity, and consequences of financial toxicity in Italy, and hopefully for fighting it. Methods: Concept elicitation, item generation and qualitative analyses represented the initial tasks of the project. Literature review, focus groups with 34 cancer patients or caregivers in three regions located in nothern, central, and southern Italy, and semi-structured interviews with 97 oncologists were conducted for concept elicitation. A recursive process was used to identify themes in the data to inform instrument until saturation was reached. Importance analysis questionnaires were administered to further 44 cancer patients to evaluate and revise the draft item pool. A multi-disciplinary committee (including oncologists, psychologists, statisticians, patient association’s representatives, nurses, social science researchers and economists) oversights the project. Results: Overall, 156 concepts were distributed among 10 themes (bureaucracy, medical care, domestic economy, emotion, family, job, health workers, welfare state, free time, transportation). After controlling for redundancy, 55 candidate items were generated and 30 items, with at least one per each theme, remained after importance analysis. Out of the 30 items, 23 (77%) refer to material conditions, 4 (13%) to psychological response and 3 (10%) to coping behaviors. Conclusions: The first results of the proFFiT project show that most of the items selected by patients are related to material conditions that cause, or derive from, financial hardship. The final questionnaire will be ready by the end of 2019. Supported by Fondazione AIRC IG grant 2017-20402. Clinical trial information: NCT03473379 .
Rapamycin Together With TGF-β1, IL-2 and IL-15 Induces The Generation Of Functional Regulatory γδT Cells From Human Peripheral Blood Mononuclear Cells
Authors: Yanjun Gu, Yongxian Hu, Kaimin Hu, Weichao Liao, Feilin Zheng, Xiaohong Yu, He Huang
Journal: Blood (2013)
Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma
Authors: Sven Borchmann, Melita Cirillo, Helen Goergen, Lydia Meder, Stephanie Sasse, Stefanie Kreissl, Paul Jan Bröckelmann, Bastian von Tresckow, Michael Fuchs, Roland Tillmann Ullrich, Andreas Engert
Journal: Journal of Clinical Oncology (2019)

PURPOSE Vitamin D deficiency is described as a modifiable risk factor for the incidence of and mortality in many common cancers; however, data in Hodgkin lymphoma (HL) are lacking. PATIENTS AND METHODS We thus performed a study measuring pretreatment vitamin D levels in prospectively treated patients with HL and correlated this with clinical outcomes. A total of 351 patients from the German Hodgkin Study Group clinical trials (HD7, HD8, and HD9) were included. RESULTS Fifty percent of patients were vitamin D deficient (&lt; 30 nmol/L) before planned chemotherapy. Pretreatment vitamin D deficiency was more common in relapsed/refractory patients than matched relapse-free controls (median baseline vitamin D, 21.4 nmol/L v 35.5 nmol/L; proportion with vitamin D deficiency, 68% v 41%; P &lt; .001). Vitamin D–deficient patients had impaired progression-free survival (10-year difference, 17.6%; 95% CI, 6.9% to 28.4%; hazard ratio, 2.13; 95% CI, 1.84 to 2.48; P &lt; .001) and overall survival (10-year difference, 11.1%; 95% CI, 2.1% to 20.2%; hazard ratio, 1.82; 95% CI, 1.53 to 2.15; P &lt; .001), consistent across trials and treatment groups. We demonstrated that vitamin D status is an independent predictor of outcome and hypothesized that vitamin D status might be important for the chemosensitivity of HL. We subsequently performed experiments supplementing physiologic doses of vitamin D (calcitriol) to cultured HL cell lines and demonstrated increased antiproliferative effects in combination with chemotherapy. In an HL-xenograft animal model, we showed that supplemental vitamin D (dietary supplement, cholecalciferol) improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. CONCLUSION On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in HL.
Wire-over-wire technique enables placement of a second parallel guidewire into a pseudocyst for drainage
Authors: Jochen Weigt, Wilfried Obst, Ali E. Canbay
Journal: Endoscopy (2019)

Recently we reported a new technique that enables the positioning of a second guidewire following a first wire without the use of a catheter [1]. Using a wire with a double-bend tip, which forms the shape of a helix, it is possible to wrap the new wire around a first guidewire and advance it. We have already successfully demonstrated this technique in biliary interventions [1]. In the following, we present the case of a patient with a symptomatic pancreatic fluid collection, in whom we used this technique to pass a second wire into the pseudocyst to allow drainage with two double-pigtail stents.
Abstract 477: Role of Telomere Dysfunction in Duchenne Muscular Dystrophy Cardiomyopathy
Authors: Asuka Eguchi, Alex C Chang, Gaspard Pardon, Beth L Pruitt, Daniel Bernstein, Helen M Blau
Journal: Circulation Research (2019)

Duchenne muscular dystrophy (DMD) is a devastating X-linked genetic disorder that affects 1 in 3500 males. Characterized by progressive muscle degeneration that culminates in respiratory failure and dilated cardiomyopathy, DMD is caused by a lack of dystrophin, a protein that provides structural support between the sarcomeric cytoskeleton and the extracellular matrix. Loss of dystrophin leads to a leaky plasma membrane, contractile stress, and disruption of cellular homeostasis. However, the molecular mechanism that eventually leads to cell death remains to be explored. Recently, the Blau lab discovered a pathogenic link between DMD cardiomyopathy and telomere dysfunction. While mdx mice that lack functional dystrophin do not exhibit dilated cardiomyopathy as in human patients, when crossed with mTR mice that lack the RNA component of telomerase (TERC), mdx mice with “humanized” telomere lengths fully manifested the severe muscle wasting and cardiac failure seen in patients. Notably, the longer telomeres, characteristic of mice, appear to be cardioprotective. Importantly, we observed telomere shortening in cardiomyocytes, but not other cell types, of DMD patients compared to age-matched controls. Preliminary data suggests that contractile stress due to the lack of dystrophin leads to a pathogenic feed-forward loop which ultimately culminates in cardiomyocyte cell death. Using human iPS cells derived from DMD patients, we have modeled telomere shortening and aspects of cardiomyocyte dysfunction characteristic of DMD, including aberrant calcium transients, mechanical stress, and arrhythmia. By comparing cardiomyocytes derived from DMD iPS cells with those from CRISPR-corrected isogenic controls on patterned bioengineered hydrogel platforms of varying stiffness, we can study the role of fibrotic stiffening in the myocardium in the premature demise of DMD cardiomyocytes. Pinpointing the early molecular events that trigger the pathogenic feed-forward loop will provide strategies for intervention to ameliorate DMD cardiomyopathy.
Autotransplantation in Patients with Multiple Myeloma and Concurrent Renal Failure Is Safe and Feasible and Associated with Recovery of Renal Function in &gt; 30% of Patients.
Authors: Gaurav C. Parikh, Rima M. Saliba, Amit Lahoti, Chitra Hosing, Floralyn Mendoza, Suhail R. Qureshi, Donna M. Weber, Michael Wang, Uday Popat, Amin Alousi, Richard E. Champlin, Sergio A. Giralt, Muzaffar H. Qazilbash
Journal: Blood (2007)
Quality improvement and implementation science in cancer care: Identifying areas of synergy and opportunities for further integration.
Authors: Devon Check, Leah L. Zullig, Melinda Davis, Angela M. Stover, Louise Davies, Florian Rudolf Schroeck, Linda Fleisher, David Chambers, Enola Proctor, Bogda Koczwara
Journal: Journal of Clinical Oncology (2019)

29 Background: Efforts to improve cancer care delivery have been driven by two approaches: quality improvement (QI) and implementation science (IS). QI and IS have developed independently but have potential for synergy. To inform efforts to better align these fields, we examined 20 cancer-related QI and IS articles to identify differences and areas of commonality. Methods: We searched PubMed for cancer care studies that used IS or QI methods and were published in the past 5 years in one of 17 leading journals. Through consensus-based discussions, we categorized studies as QI if they evaluated efforts to improve the quality, value, or safety of care, or IS if they evaluated efforts to promote the adoption of evidence-based interventions into practice. We identified the 10 most frequently cited studies from each category (20 total studies), characterizing and comparing their objectives, methods – including use of theoretical frameworks involvement of stakeholders – and terminology. Results: All IS studies (10/10) and half (5/10) of QI studies addressed barriers to uptake of evidence-based practices. The remaining five QI studies sought to improve clinical outcomes, reduce costs, and/or address logistical issues. QI and IS studies employed common approaches to change provider and/or organizational practice (e.g., training, performance monitoring/feedback, decision support). However, the terminology used to describe these approaches was inconsistent within and between IS and QI studies. Fewer than half (8/20) of studies (4 from each category) used a theoretical or conceptual framework and only 4/20 (2 from each category) consulted key stakeholders in developing their approach. Most studies (10/10 IS and 6/10 QI) were multi-site, and most were observational, with only 4/20 studies (2 from each category) using a randomized design to evaluate their approach. Conclusions: Cancer-related QI and IS studies had overlapping objectives and used similar approaches but used inconsistent terminology. The impact of IS and QI on cancer care delivery could be enhanced by greater harmonization of language and by promoting rigor through the use of conceptual frameworks and stakeholder input.
Monoclonal Gammopathy and Hypogammaglobulinemia As Prognostic Factors in Patients with Chronic Lymphocytic Leukemia: A Retrospective Multicentric Experience
Authors: Idanna Innocenti, Andrea Corbingi, Nicola Piccirillo, Francesco Autore, Andrea Visentin, Edoardo Scomazzon, Ramona Cassin, Raffaella Pasquale, Francesca Morelli, Simona Sica, Gianluigi Reda, Livio Trentin, Luca Laurenti
Journal: Blood (2018)
Abstract 271: Reduced Expression of the Cardiac Sodium Channel Nav1.5 Triggers Enhanced Fatty Acid Metabolism and Oxidative Stress
Authors: Ryan L Boudreau, Xiaoming Zhang, Jared M McLendon, William Kutschke, Ethan J Anderson, Barry London
Journal: Circulation Research (2019)

SCN5A encodes the voltage-gated Na+ channel Nav1.5 that is best known for its role in cardiac conduction. We recently identified a microRNA (miR-24) binding site within the SCN5A coding region and found that its activity is modulated by an adjacent synonymous SNP (rs1805126). In humans, we linked the rs1805126 minor allele with decreased cardiac SCN5A expression and increased non-arrhythmic death in HF patients. To understand how lower SCN5A expression may lead to worse HF, we evaluated SCN5A +/- haploinsufficient mice, which develop cardiac fibrosis after 12 months of age. Given that oxidative stress often precedes fibrosis and is increased in HF, we assessed ROS levels in SCN5A +/- mouse hearts and found a 2.5-fold increase relative to wildtype (WT) hearts. We also performed co-expression analyses using human cardiac mRNA profiling data and unexpectedly found that SCN5A is linked to PPARA , a key driver of fatty acid oxidation (FAO, a predominant source of cardiac ROS), and to gene networks related to glucose metabolism and oxidative phosphorylation (OXPHOS). Along these lines, we found that SCN5A +/- mouse hearts show mRNA changes indicative of increased FAO/OXPHOS and decreased glycolysis, with a coincident broad up-regulation of PPAR target genes. Metabolomics data further indicated that glycolytic flux is perturbed in SCN5A +/- mouse hearts, and cardiac myofiber respiration assays showed that these hearts exhibit enhanced FAO. To test if SCN5A +/- mice suffer worse HF outcomes, we subjected young adult male mice to thoracic aortic constriction (TAC), a model of cardiac hypertrophy progressing to HF. While WT mice showed typical hypertrophic responses and signs of HF, SCN5A +/- hearts were resistant to TAC-induced hypertrophy, which based on prior reports, may be the result of elevated FAO. Overall, our data support the notion that lower cardiac SCN5A expression leads to an overreliance on FAO and accumulation of ROS in heart, which may exacerbate HF in patients. Together, our studies point to unforeseen roles for Nav1.5 in cardiac metabolism, opening several new paths of investigation. Future studies will interrogate 1) if human hearts with low SCN5A expression show signs of oxidative stress, and 2) if SCN5A +/- mice suffer worse HF after myocardial infarction.
Should Myelodysplastic Syndromes in Very Old Patients be More Actively Managed? Clinical Characteristics, Management and Outcomes for Patients 85 Years and Older
Authors: Laura McDonald, Peter McCarthy, Mohammad Khan, Patrick Hogan, Eileen C. Kelleher, Philip Murphy, John Quinn, Ronan Desmond, Johnny McHugh, Melanie Strickland, Mary Cahill, Su Wai Maung, Clodagh Keohane, Desmond O'Neill, Daniel Ryan, Vitaliy Mykytiv, Helen Enright
Journal: Blood (2018)