tbuckley/cabot-search huggingface dataset:
Duration of First Remission in Diffuse Large B-Cell Lymphoma (DLBCL) Define Groups of Patients with Different Overall Survival Which Cannot Be Entirely Distinguished by Clinical Features or IPI at Diagnosis: a Prospective Population Based Study of the Scotland and Newcastle Lymphoma Group
Authors: Michal Sieniawski, Jennifer Wilkinson, Dominic Culligan, John Davies, John Goodlad, Ruth Jarrett, Anne L Lennard, Helen Lucraft, Tryfonia Mainou-Fowler, Pam McKay, Fiona Scott, Sudhir Tauro, Jo White, Stephen J Proctor
Journal: Blood (2008)
Abstract 175: Evaluation of Sepsis-Related Cytokines on Endothelial Cell Permeability
Authors: Carmen E Campbell, William A Boisvert
Journal: Circulation Research (2019)

The endothelium plays a critical role in the progression from sepsis to organ failure because endothelium lines all blood vessels and organs in the body to provide a selective barrier. The endothelium is responsible for dynamically regulating the passage of small molecules, fluid, and cells between the bloodstream and tissues. In sepsis, many factors play a role in compromising the endothelium. Dysfunctional endothelium results in development of capillary leak, tissue hypoperfusion, hypoxia, edema, and shock. This study evaluates the individual contributions immunomodulatory cytokines as well as a potential synergistic effect of cytokine combinations on vascular endothelial permeability. Major components of intercellular junctions including tight junction and associated cell adhesion molecules are also assessed microscopically. Specifically, endothelial cell monolayer response to an array of sepsis-related factors including TNF-alpha, IL-1b, IL-6, IL- 8, IL-10, IL-12, IFN-g, and TGF-b by a novel approach using the in-vitro Electric Cell-substrate Impedance Sensing (ECIS) biosensor model is presented.
Retrospective evaluation of clinical evidence submitted with off-label requests at a community-based oncology infusion center.
Authors: Matthew Stankowicz, David M. Heyer
Journal: Journal of Clinical Oncology (2019)

254 Background: A systematic grading system was created to evaluate literature submitted with off-label requests to the Inova Schar Cancer Institute (ISCI) oncology P&amp;T. Level of evidence (LOE) 1A, 1B, and 1C are granted immediate approval. LOE 2A, 2B, 2C require two members (MD and PharmD) to approve. LOE 3A, 3B, 3C require 3/4 (2MDs, 2PharmDs) members to approve. LOE no benefit (NB) is denied approval. Methods: Identified off-label requests for hematology/oncology patients from December 23, 2016 to January 2, 2019. Primary objective was retrospective evaluation of literature submitted using a systematic grading system through the oncology P&amp;T. Secondary objective was to evaluate financial and clinical outcomes of off-label treatments, including compliance with Quality Oncology Practice Initiative measures. Future aim is to compare LOE and treatment outcomes pre- and post-implementation. Results: There were 73 off-label requests with 126 references submitted as supporting literature. The most frequently requested treatments were nivolumab (21.9%) and pembrolizumab (20.5%). The most common disease state was breast cancer. The LOE for the literature submitted was 1A (10.3%), 1B (23%), 1C (8.7%), 2A (9.5%), 2B (7.9%), 2C (4.8%), 3A (1.6%), 3B (7.1%), 3C (5.6%), and NB (21.4%). Sixty-six treatments were approved and 54 patients received at least one dose of off-label treatment. Thirty off-label requests were made based on molecular tumor board recommendations. Off-label treatment was discontinued for disease progression (29.6%), toxicity (25.9%), or death (14.8%). Three patients completed therapy and 11 received subsequent treatment after discontinuation of the off-label treatment. Average time from last treatment to death was 41.8 days (median 21, range 6-175). Eleven of 55 expired patients received hospice care prior to expiring. Most off-label treatments were approved by third party insurance (55.6%) while 37% were covered by manufacturer provided free drug and 7.4% were paid for by the ISCI Foundation. Conclusions: The standardized grading system for off-label treatments can be implemented to ensure safe and effective use of off-label treatments in oncology patients.
Hierarchical microchanneled scaffolds modulate multiple tissue-regenerative processes of immune-responses, angiogenesis, and stem cell homing
Authors: Jong-Eun Won, Yun Sang Lee, Jeong-Hui Park, Jung-Hwan Lee, Yoo Seob Shin, Chul-Ho Kim, Jonathan C. Knowles, Hae-Won Kim
Journal: Biomaterials (2019)

Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured ('microchanneled') 3D printed scaffolds (named 'μCh'), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The μCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of μCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the μCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the μCh. Furthermore, the neo-blood vessel formation was more pronounced in the μCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the μCh. Further assays on the protein sequestration to the μCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the μCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the μCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the μCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the μCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms.
First Line Therapy With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) In Patients With AL Amyloidosis and Potentially Reversible Contraindications To Autologous Stem Cell Transplant
Authors: Giovanni Palladini, Paolo Milani, Marta Vidus Rosin, Andrea Foli, Giampaolo Merlini
Journal: Blood (2013)
Combination of CD19 and CD70 Specific Chimeric Antigen Receptor T Cells Achieves Long-Term Disease-Free Survival in Relapsed and Refractory Primary Central Nervous System Diffuse Large B Cell Lymphoma
Authors: Sanfang Tu, Rui Huang, Xuan Zhou, Yanjie He, Zhao Liang, Lei Wang, Lung-Ji Chang, Yuhua Li
Journal: Blood (2018)
Improving time to start bone modifying agents in newly diagnosed multiple myeloma patients.
Authors: Sarah Lee, Nathaniel Rosko, Janice Reed, Mary Ann Karam, Beth Faiman, Saveta Mathur, Kimberly Hamilton, Alex V. Mejia, Faiz Anwer, Christy Joy Samaras, Jason Neil Valent
Journal: Journal of Clinical Oncology (2019)

65 Background: Current ASCO and IMWG guidelines recommend all patients (pts) on active myeloma therapy receive concurrent supportive care with a bone modifying agent (BMA) to decrease the risk of skeletal related events (SRE). Unfortunately, recent data shows only 51% of Medicare pts with myeloma received a BMA within 90 days of first chemotherapy. We implemented a quality improvement project to identify the average time to BMA initiation at all Cleveland Clinic affiliated sites, with the primary goal to improve time to start BMA in newly diagnosed multiple myeloma (NDMM) pts by 4 weeks at Cleveland Clinic Main Campus (MC). Methods: Barriers to start BMA were identified using quality improvement tools developed at ASCO Quality Training Program. The first PDSA cycle ran from Sept 2018–Jan 2019 with an emphasis on education. This included review of updated guidelines, literature review of risks and toxicities associated with BMAs, and strategies for choosing BMA based on pt factors. Baseline data on time to start BMA and data to evaluate impact of PDSA intervention was done by chart review. Results: 161 NDMM pts were evaluated from 2015–2018 at all sites. The average time difference between the start of myeloma therapy and the start date of BMA in NDMM pts was 10.5 weeks. Subset analysis based on whether pts were treated at MC vs affiliate site was 10.6 weeks vs 9.1 weeks, respectively. During the first PDSA cycle, 14 NDMM pts were treated at MC. 86% (12/14) pts were treated with BMA. The average time between cycle 1 day 1 of first line treatment and first dose BMA was 4.3 weeks (range 4-12 weeks). Conclusions: With increased physician education and awareness of internal baseline data, we achieved our initial goal and observed a significant improvement in time to start BMA from 10.5 weeks to 4.3 weeks. Obstacles regarding effective communication with patients on the benefit of BMAs as well as need for dental clearance were barriers identified early on. We plan to incorporate BMA guidelines in our institutional care path with the goal to decrease time to initiation at all affiliated practices. Further mechanisms to ensure reinforcement of BMA initiation in NDMM patients is warranted to maintain therapeutic benefit.
Financial hardship associated health care utilization among cancer survivors in the United States.
Authors: Zhiyuan Zheng, Reginald Tucker-Seeley, Xuesong Han, Jingxuan Zhao, Matthew P. Banegas, Ashish Rai, Ahmedin Jemal, K Robin Yabroff
Journal: Journal of Clinical Oncology (2019)

133 Background: A cancer diagnosis is associated with medical financial hardship in the U.S. However, little is known about health consequences associated with financial hardship. This study examines associations between medical and non-medical financial hardship on healthcare utilization among cancer survivors. Methods: We used the National Health Interview Survey (2013-2017) to identify cancer survivors (18-64 years: n = 5200; 65+ years: n = 7326). Medical financial hardship included material (e.g., problems paying medical bills), psychological (e.g., worry about medical bills), and behavioral (e.g., forgoing care due to cost) domains, and non-medical financial hardship included food hardship and worry for other financial needs (e.g. retirement, monthly bills, standard of living, and housing costs). We compared cancer survivors by intensities of medical and non-medical financial hardships in: 1) emergency department (ED) visits; 2) preventive services use (receipt of influenza vaccine, and blood pressure/cholesterol screenings); and 3) cervical/breast/colorectal cancer screenings among eligible cancer survivors. We used generalized ordinal logistic regressions, controlling for demographic characteristics, time since diagnosis, number of cancer diagnoses, insurance, income, and comorbidities. Results: Across age groups, both higher medical and non-medical hardship intensities were associated with higher ED visits and lower use of preventive services. Compared to cancer survivors with lowest intensity, higher percentages of ED visits were observed among those with highest medical hardship intensity (ages 18-64: 42% vs 26.2%; ages 65+: 37.2% vs 27.9%, all p &lt; .01) and highest non-medical hardship intensity (ages 18-64: 37.6% vs 24.3%, p = .01). Moreover, compared to lowest intensity, highest medical hardship intensity was associated with lower influenza vaccination (ages 18-64: 45.6% vs 52.5%; ages 65+: 64.6% vs 75.6%, p &lt; .05) and breast cancer screening (54.4% vs 65.9%, p &lt; .05). Conclusions: Cancer survivors with higher medical and non-medical financial hardships have more ED visits and medical financial hardship was also associated with less use of preventive services and some cancer screening.
Abstract 746: The Effect of Aging-related Metabolic Disorder on Resistin Expression and Valvular Heart Disorder
Authors: Rihab Bouchareb, Najla Saadallah, Roger Hajjar, Djamel Lebeche
Journal: Circulation Research (2019)

Calcific aortic valve stenosis (AS) is the most prevalent valvular heart disease and the third most frequent cardiovascular disease after coronary artery disease and hypertension. AS is characterized by a period of asymptomatic progressive valve calcification, which eventually leads to the development of a severe stenosis and to the onset of symptoms. Visceral obesity is a strong predictor of type-2 diabetes and is associated with insulin resistance. In addition, increased visceral adiposity leads to an increase in systemic release in resistin (Retn) and possibly interleukins. Elevation of circulating adipokines such as Retn plays a role in the development of muscle insulin resistance. Moreover, higher Retn levels were associated with increased valvular inflammation and calcification in the elderly patients, whereas this association was not observed among middle-aged patients. In the current study, we explored the potential role of Retn in ectopic valvular calcification. Analyses of scanning electron microscopy micrographs of calcified aortic valve showed that Retn is more abundant next to calcified nodes. These data corroborate with increased levels of circulating Retn in apoE mice that were fed a high fat high sucrose diet for 24 weeks. Moreover, apoE-/-Retn-/- double KO mutant mice have lower plasma cholesterol level compared to apoE KO mice. In addition, knocking down Retn decreased valve lipid infiltration, lowered glycaemia, calcium nodes and reduced fibrosis. In conclusion, Retn may be a new pharmacological target to stop the progression of aortic stenosis in patients with visceral obesity.
The rationale of rationalization
Authors: Walter Veit, Joe Dewhurst, Krzysztof Dołęga, Max Jones, Shaun Stanley, Keith Frankish, Daniel C. Dennett
Journal: Behavioral and Brain Sciences (2020)

While we agree in broad strokes with the characterisation of rationalization as a "useful fiction," we think that Fiery Cushman's claim remains ambiguous in two crucial respects: (1) the reality of beliefs and desires, that is, the fictional status of folk-psychological entities and (2) the degree to which they should be understood as useful. Our aim is to clarify both points and explicate the rationale of rationalization.
An Optimised In Vivo Modelling System For Adult Acute Lympoblastic Leukaemia (ALL) Enables Sensitive Detection Of Leukaemia Initiating Cells (LIC) and Drug Resistant Clones
Authors: Bella Patel, Aditi Dey, Anna Z Castleton, Claire Schwab, Brendan Beaton, Nahid Zareian, Christie Zhang, Anthony V Moorman, Adele Fielding
Journal: Blood (2013)
"Secondary Chronic Myeloid Leukemia": Comparison between Patients Previously Exposed or Not to Chemo and/or Radiotherapy
Authors: Francesco Autore, Federica Sora, Patrizia Chiusolo, Mario Annunziata, Alessandra Iurlo, Daniele Cattaneo, Sara Galimberti, Jolanta Bayer, Giuseppe Leone, Simona Sica
Journal: Blood (2018)
Abstract 334: Cardiac Myosin Binding Protein C Phosphorylation Regulates Calcium Homeostasis
Authors: Mohit Kumar, Kobra Haghighi, Evangelia Kranias, Sakthivel Sadayappan
Journal: Circulation Research (2019)

Rationale: Cardiac myosin binding protein-C (cMyBP-C) is heavily phosphorylated to regulate normal cardiac function under basal conditions. However, its phosphorylation level is significantly decreased in patients with heart failure and atrial fibrillation. Furthermore, decreased cMyBP-C phosphorylation causes reduced myofilament contractility and decreased calcium sensitivity. The impact of such decreases in cMyBP-C phosphorylation and myofilament calcium sensitivity on the overall calcium handling and potential induction of arrhythmogenesis is not known. Objective: To determine the necessity and sufficiency of cMyBP-C phosphorylation to regulate calcium cycling and contractility at the isolated cardiomyocyte level. Methods and Results: Contractile properties and calcium kinetics were measured in intact cardiomyocytes isolated from 3-month-old, mixed sex, mice expressing phospho-ablated (S273A/S282A/S302A) cMyBP-C (AAA) or phospho-mimetic (S273D/S282D/S302D) cMyBP-C (DDD) and nontransgenic (NTG) control mice. AAA cells displayed a significant decrease in fractional shortening compared to NTG and DDD cells (9.4% vs 12.8% in NTG, and 12.3% in DDD, p&lt;0.0001). Similarly, AAA myocytes demonstrated abnormal calcium kinetics with increased diastolic calcium levels (20%, p&lt;0.001 vs . NTG and DDD) and prolonged decay time of the calcium transient (26%, p&lt;0.01 vs NTG and DDD) when compared with NTG and DDD myocytes. Caffeine-induced calcium release in AAA myocytes indicated no change in SR calcium content, while sodium-calcium exchanger function, assessed as the time constant (τau) of calcium decline, was increased (89%, p&lt;0.01 vs NTG). However, these depressive effects in AAA myocytes were relieved by isoproterenol (100 nmol/L) stimulation. Furthermore, stress conditions (2 Hz + ISO) increased after-contractions in AAA cardiomyocytes (60% in AAA vs 13% in NTG, p&lt;0.001 and 15% in DDD, p&lt;0.001). In addition, preliminary data indicate increased susceptibility of the AAA mice to arrhythmias under stress conditions in vivo. Conclusion: Dephosphorylation of cMyBP-C is sufficient to reduce sarcomere contractility and impair calcium cycling resulting in spontaneous after-contractions and arrhythmias under stress conditions.
Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial
Authors: Stijn F H Raven, Christian J P A Hoebe, Ann C T M Vossen, Leo G Visser, Jeannine L A Hautvast, Anna H E Roukens, Jim E van Steenbergen
Journal: The Lancet Infectious Diseases (2019)
Superior Immunomodulatory Effects of Cultured Mast Cells: Potent Strategy for Treatment of Gvhd
Authors: Raita Araki, Hideaki Maeba, Rie Kuroda, Toshihiro Fujiki, Shintaro Mase, Shoichi Koizumi, Akihiro Yachie, Ryosei Nishimura
Journal: Blood (2012)
Mutational Loss of PTEN Induces Resistance to NOTCH1 Inhibition in T-ALL.
Authors: Adolfo Ferrando, Teresa Palomero, Maria Luisa Sulis, Maria Cortina, Pedro J. Real, Kelly Barnes, Maria Ciofani, Esther Caparros, Sherrie L. Perkins, Govind Bhagat, Archana Mishra, Giuseppe Basso, Ramon Parsons, Juan Carlos Zúniga-Pflücker, Maria Dominguez
Journal: Blood (2007)
Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication
Authors: Shintaro Katayama, Katarina Stenberg Hammar, Kaarel Krjutškov, Elisabet Einarsdottir, Gunilla Hedlin, Juha Kere, Cilla Söderhäll
Journal: European Respiratory Journal (2019)

Background Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. Methods We analysed leukocyte transcriptomes from preschool children (6 months–3 years) at acute wheeze (n=107), and at a revisit 2–3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. Findings Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p&lt;0.005) in infancy, and asthma medication and FEV 1 %/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p&lt;0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668–0.962). Interpretation Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma.
Serum Beta-2 Microglobulin Predicts the Survival Outcome after Autologous Stem Cell Transplantation in Relapse or Refractory Diffuse Large B Cell Lymphoma
Authors: Hyeun-Su Im, Jung Yong Hong, Dok Hyun Yoon, Shin Kim, Jung Sun Park, Sang Wook Lee, Chan-Sik Park, Jin-Sook Ryu, Jooryung Huh, Cheolwon Suh
Journal: Blood (2018)
Abstract 107: Role of p53 Acetylation in Mediating Myocardial Angiogenesis and Diabetic Cardiomyopathy
Authors: Heng zeng, Jian Xiong Chen
Journal: Circulation Research (2019)

The prevalence of diabetic heart failure (HF) is increasing at an alarming rate, it is therefore urgent to identify potential therapeutic targets. Accumulating evidence demonstrates the important role of acetylation of mitochondrial proteins in HF and diabetes. In this study, we investigated the role of p53 acetylation in diabetic impairment of myocardial angiogenesis and determine whether inhibition of p53 acetylation can improve cardiac function in the setting of diabetes. The acetylation of p53 was significantly increased in hearts of diabetic db/db mice, hyperglycemic STZ mice, and high fat-diet-induced obese mice, which was associated with the reduced level of SIRT3. Knockout of SIRT3 increased p53 acetylation, which in turn led to impairment of angiogenesis and cardiac function in mice. Using cultured cardiomyocytes exposed to high glucose (HG) and diabetic db/db mice, we further explored the roles of p53 acetylation on angiogenic growth factor expression, angiogenesis and cardiac function. We found that exposure of cardiomyocytes to HG resulted in upregulation of p53 acetylation. This was accompanied by a reduction of Sirt3 expression. Transfection with Ad-Sirt3 significantly reduced hyperglycemia-induced p53 acetylation. Overexpression of Sirt3 increased the expression of HIF-1α and Ang-1 and VEGF, together with reduction of oxygen consumption and ROS formation. Hyperglycemia-induced caspase-3 expression and apoptosis was also significantly suppressed by Sirt3. Knockdown of p53 in cardiomyocytes by using siRNA significantly increased the expression of HIF-1α and Ang-1 and VEGF. Treatment with p53 siRNA significantly decreased oxygen consumption. In vivo , Ad-Sirt3 treatment significantly inhibited p53 acetylation in the heart of db/db mice. Ad-Sirt3 treatment upregulated the expression of HIF-1α, Ang-1 and VEGF. Similarly, mutations at acetylation sites K117/161/162 and K98 of p53 (p53 4KR ) upregulated the expression of HIF-1α and increased angiogenesis in mouse heart. Ad-Sirt3 treatment increased angiogenesis, and reduced ROS formation and apoptosis in the diabetic heart. These led to significantly improved cardiac function. Our study suggests that p53 acetylation may be a novel target for diabetic cardiomyopathy.