tbuckley/cabot-search huggingface dataset:
Phase II Study Evaluating the Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem and Progenitor Cells for Allogeneic Hematopoietic Cell Transplantation and Phenotypic Characterization of the Leukapheresis Product
Authors: Michael P. Rettig, Geoffrey L. Uy, Asad Bashey, Steven Devine, Samantha Jaglowski, Abi Vainstein, Ella Sorani, Hemda Chen, Osnat Bohana-Kashtan, Stephen Shaw, Peter Westervelt, John F. DiPersio
Journal: Blood (2018)
Assessing hematologic ratios as biomarkers for psychosocial distress.
Authors: Abigail Fong, Kelly Lafaro, Arthur X Li, Laleh Golkar Melstrom, Jenny Rodriguez, Karen L. Clark, Matthew J. Loscalzo, Susanne Warner
Journal: Journal of Clinical Oncology (2019)

699 Background: Psychosocial distress is common among cancer patients and has been shown to have deleterious effects on a patient’s quality of life, treatment, and outcomes. Neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-monocyte ratio (PMR) have been associated with poor outcomes in some cancers. Therefore we hypothesized that these ratios may be correlated to distress. This study looked at request for social work follow up as a surrogate marker for distress and investigated relationships between these ratios and markers of patient distress. Methods: A validated 48 item electronic distress screen was administered to patients in the medical and surgical oncology clinics of a large cancer center from 2009-2015. Patient requests for social work follow up were noted and patient charts reviewed for relevant labs and history. Patient demographics, NLR, LMR, PMR were reviewed. Chi-squared tests and univariate and multivariate regressions were performed to compare groups and relationships of variables and outcomes. Results: 43% of patients surveyed requested social work follow up. Of those, 75% received follow up, at a mean of 8 days. Non-Caucasian patients were more likely to request social work follow up (p = 0.03). Non-English speaking patients (p = 0.06) and those who saw medical oncologists trended towards significant desire for social work follow up. There was no significant correlation between NLR, PMR, LMR and desire to see a social worker. On multivariate analysis, patients with metastatic disease were less likely to want social work follow up (OR 0.43, 95% CI: 0.21-0.9, P = 0.02). Conclusions: In this study, non-white, non-English speaking patients, and those seeing medical oncologists were more likely to request social work follow up. We found no significant correlations between NLR, PMR, LMR and request for social work follow up. This suggests that desire for social work follow up is not a good correlate for physiologic distress in cancer patients. Further work is ongoing to provide better insight into determinants of psychosocial and physiologic stress in this patient population along with relevance of hematologic ratios.
CARs of the future
Authors: Anthony F. Daniyan, Renier J. Brentjens
Journal: American Journal of Hematology (2019)

CAR T cells have revolutionized the treatment of relapsed and refractory CD19‐positive leukemia and lymphoma. Unfortunately, the majority of patients treated will not achieve durable remissions. Reasons for these suboptimal clinical outcomes can be tied back to intrinsic CAR T cell design and manufacturing processes, factors that are highly amenable to modification and improvement. As CAR T cell therapy is being deployed in spaces outside of CD19‐positive disease, these limitations, complications, and setbacks need to be overcome, allowing for the full potential of this novel therapy to be realized. Preclinical work has begun tackling these major roadblocks, paving the way for potentially off‐the‐shelf products that are safer and more potent. In time, a number of these advances will be translated to the clinic and usher in an era of CARs of the future.
Salvage Autologous Stem Cell Transplantation in Multiple Myeloma: Investigating the Impact of Pre-Transplant Therapy
Authors: Kevin C. Miller, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, Martha Q. Lacy, Angela Dispenzieri, David Dingli, Prashant Kapoor, Wilson I Gonsalves, Taxiarchis Kourelis, William J. Hogan, Shaji K. Kumar
Journal: Blood (2018)
Abstract 13114: Telomere Length is Not Associated With Known Cardiovascular Risk Factors in Older Patients (≥75 Years) with Acute Coronary Syndrome Treated by Invasive Strategy
Authors: Meedya Sharifpour, Hannah Sinclair, Murugapathy Veerasamy, Jin Tee, Dermot Neely, Carmen Martin-Ruiz, Weiliang Qiu, Vijay Kunadian
Journal: Circulation (2014)

Background: Telomere length (TL) is emerging as a promising biomarker for cardiovascular ageing. In younger patients (≤65 years), TL is associated with risk factors for acute coronary syndrome (ACS...
Premature Aging in Young Cancer Survivors
Authors: Saro H Armenian, Christopher J Gibson, Russell C Rockne, Kirsten K Ness
Journal: JNCI Journal of the National Cancer Institute (2018)

Advances in early detection, treatment, and supportive care have resulted in an estimated 16 million cancer survivors who are alive in the United States today. Outcomes have notably improved for children with cancer as well as young adults with hematologic malignancies due, in part, to the intensification of cancer treatment, including the use of hematopoietic cell transplantation. Emerging evidence suggests that these cancer survivors are at risk for premature aging, manifesting as early onset of chronic health conditions and a higher risk of mortality compared with the general population. Although the pathophysiology of premature aging in these survivors has not been fully elucidated, emerging concepts in aging research could help shed light on this phenomenon. Longitudinal studies are needed to better characterize aging in these survivors, setting the stage for much-needed interventions to halt the trajectory of accelerated aging. These efforts will be enhanced through collaborations between translational researchers, clinical oncologists, primary care providers, geriatricians, patient caretakers, and other stakeholders committed to improving the lives of the growing population of survivors.
Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns
Authors: Gaurav A. Upadhyay, Tharian Cherian, Dalise Y. Shatz, Andrew D. Beaser, Zaid Aziz, Cevher Ozcan, Michael T. Broman, Hemal M. Nayak, Roderick Tung
Journal: Circulation (2019)

Septal activation in patients with left bundle-branch block (LBBB) patterns has not been described previously. We performed detailed intracardiac mapping of left septal conduction to assess for the presence and level of complete conduction block (CCB) in the His-Purkinje system. Response to His bundle pacing was assessed in patients with and without CCB in the left bundle.Left septal mapping was performed with a linear multielectrode catheter in consecutive patients with LBBB pattern referred for device implantation (n=38) or substrate mapping (n=47). QRS width, His duration, His-ventricular (HV) intervals, and septal conduction patterns were analyzed. The site of CCB was localized to the level of the left-sided His fibers (left intrahisian) or left bundle branch. Patients with ventricular activation preceded by Purkinje potentials were categorized as having intact Purkinje activation.A total of 88 left septal conduction recordings were analyzed in 85 patients: 72 LBBB block pattern and 16 controls (narrow QRS, n=11; right bundle-branch block, n=5). Among patients with LBB block pattern, CCB within the proximal left conduction system was observed in 64% (n=46) and intact Purkinje activation in the remaining 36% (n=26). Intact Purkinje activation was observed in all controls. The site of block in patients with CCB was at the level of the left His bundle in 72% and in the proximal left bundle branch in 28%. His bundle pacing corrected wide QRS in 54% of all patients with LBBB pattern and 85% of those with CCB (94% left intrahisian, 62% proximal left bundle-branch). No patients with intact Purkinje activation demonstrated correction of QRS with His bundle pacing. CCB showed better predictive value (positive predictive value 85%, negative predictive value 100%, sensitivity 100%) than surface ECG criteria for correction with His bundle pacing.Heterogeneous septal conduction was observed in patients with surface LBBB pattern, ranging from no discrete block to CCB. When block was present, we observed pathology localized within the left-sided His fibers (left intrahisian block), which was most amenable to corrective His bundle pacing by recruitment of latent Purkinje fibers. ECG criteria for LBBB incompletely predicted CCB, and intracardiac data might be useful in refining patient selection for resynchronization therapy.
Comprehensive Analysis of Systemic Immunosuppression (SIS) Duration after Allogeneic Hematopoietic Stem Cell Transplant: Risk Score Model Provides Stratification of Patients According to Probability of SIS Discontinuation
Authors: Maria Rhida Bautista, Arjun Law, Wilson Lam, Fotios V. Michelis, Santhosh Thyagu, Auro Viswabandya, Rajat Kumar, Jeff H. Lipton, Hans A. Messner, Dennis Dong Hwan Kim
Journal: Blood (2018)
Clonal <i>MET</i> Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer
Authors: Gillianne G.Y. Lai, Tse Hui Lim, John Lim, Perry J.R. Liew, Xue Lin Kwang, Rahul Nahar, Zaw Win Aung, Angela Takano, Yin Yeng Lee, Dawn P.X. Lau, Gek San Tan, Sze Huey Tan, Wan Ling Tan, Mei-Kim Ang, Chee Keong Toh, Bien Soo Tan, Anantham Devanand, Chow Wei Too, Apoorva Gogna, Boon Hean Ong, Tina P.T. Koh, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Tanujaa Rajasekaran, Ju Yuan, Tony Kiat Hon Lim, Alvin S.T. Lim, Axel M. Hillmer, Wan Teck Lim, N. Gopalakrishna Iyer, Wai Leong Tam, Weiwei Zhai, Eng-Huat Tan, Daniel S.W. Tan
Journal: Journal of Clinical Oncology (2019)

Mesenchymal epithelial transition factor ( MET) activation has been implicated as an oncogenic driver in epidermal growth factor receptor ( EGFR)-mutant non-small-cell lung cancer (NSCLC) and can mediate primary and secondary resistance to EGFR tyrosine kinase inhibitors (TKI). High copy number thresholds have been suggested to enrich for response to MET inhibitors. We examined the clinical relevance of MET copy number gain (CNG) in the setting of treatment-naive metastatic EGFR-mutant-positive NSCLC.
Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes
Authors: Wu-Lin Zuo, Jing Yang, Yael Strulovici-Barel, Jacqueline Salit, Mahboubeh Rostami, Jason G. Mezey, Sarah L. O'Beirne, Robert J. Kaner, Ronald G. Crystal
Journal: European Respiratory Journal (2019)

Airway remodelling in chronic obstructive pulmonary disease (COPD) originates, in part, from smoking-induced changes in airway basal stem/progenitor cells (BCs). Based on the knowledge that bone morphogenetic protein 4 (BMP4) influences epithelial progenitor function in the developing and adult mouse lung, we hypothesised that BMP4 signalling may regulate the biology of adult human airway BCs relevant to COPD. BMP4 signalling components in human airway epithelium were analysed at the mRNA and protein levels, and the differentiation of BCs was assessed using the BC expansion and air–liquid interface models in the absence/presence of BMP4, BMP receptor inhibitor and/or small interfering RNAs against BMP receptors and downstream signalling. The data demonstrate that in cigarette smokers, BMP4 is upregulated in ciliated and intermediate undifferentiated cells, and expression of the BMP4 receptor BMPR1A is enriched in BCs. BMP4 induced BCs to acquire a smoking-related abnormal phenotype in vitro mediated by BMPR1A/Smad signalling, characterised by decreased capacity to differentiate into normal mucociliary epithelium, while generating squamous metaplasia. Exaggerated BMP4 signalling promotes cigarette smoking-relevant airway epithelial remodelling by inducing abnormal phenotypes in human airway BCs. Targeting of BMP4 signalling in airway BCs may represent a novel target to prevent/treat COPD-associated airway disease.
Ruxopeg, a Multi-Center Bayesian Phase 1/2 Adaptive Randomized Trial of the Combination of Ruxolitinib and Pegylated Interferon Alpha 2a in Patients with Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis
Authors: Jean-Jacques Kiladjian, Juliette Soret-Dulphy, Matthieu Resche-Rigon, Francoise Boyer-Perrard, Fiorenza Barraco, Valérie Rolland-Neyret, Claude Capron, Sylvie Chevret, Stephane Giraudier, Bruno Cassinat
Journal: Blood (2018)
Abstract 19954: Echocardiographic Findings in Pediatric Patients Evaluated for Systemic Hypertension
Authors: Michelle Kaplinski, Heather Griffis, Fang Liu, Craig Tinker, Nina C Laney, Melodee Mendoza, Meryl S Cohen, Kevin Meyers, Shobha Natarajan
Journal: Circulation (2017)

Introduction: Elevated left ventricular (LV) mass and abnormal LV mechanics have been associated with adverse cardiovascular events in adults and differ by race and body mass index (BMI). Cardiovas...
Transforming the food system to fight non-communicable diseases
Authors: Francesco Branca, Anna Lartey, Stineke Oenema, Victor Aguayo, Gunhild A Stordalen, Ruth Richardson, Mario Arvelo, Ashkan Afshin
Journal: BMJ (2019)

Malnutrition and unhealthy diets are important risk factors for non-communicable diseases. <b>Francesco Branca and colleagues</b> call for changes in both what and how food is produced, marketed, and consumed
Abstract 20107: An Injectable CCN1-Collagen Matrix for Cardiac Cell Support and Improving Left Ventricular Function Post Myocardial Infarction
Authors: Brian McNeill, Branka Vulesevic, Danielle Giroux, Nicholas Blackburn, Marc Ruel, Erik J Suuronen
Journal: Circulation (2017)

Background: Biomaterials have emerged as a promising approach to treat myocardial infarction (MI). Here we investigated a collagen matrix loaded with the pro-angiogenic, anti-fibrotic matricellular protein CCN1. We hypothesized that a CCN1-matrix can positively regulate the function of different cardiac cells and that it would limit adverse cardiac remodeling and dysfunction in a mouse MI model. Methods: In vitro experiments examined the function of heart-derived fibroblasts, cardiomyocytes and bone marrow macrophages when cultured on the CCN1-matrix. In vivo, MI was induced in mice and at 1wk post-MI, mice received intramyocardial injections of: 1) PBS; 2) matrix; or 3) CCN1-matrix. Heart function was assessed by echocardiography and tissues were analyzed by histology. Results: In vitro studies revealed that CCN1-matrix was able to reduce fibroblast proliferation by 29% (p=0.02), and TGF-β mediated induction of the myofibroblast marker α-SMA by 42.1% (p=0.014), compared to matrix culture. Furthermore, CC...
Clinical Relevance of NOTCH1 Mutations in Ibrutinib-Treated Chronic Lymphocytic Leukemia (CLL)
Authors: Giovanni Del Poeta, Luca Laurenti, Annalisa Chiarenza, Francesca Maria Rossi, Massimiliano Postorino, Riccardo Bomben, Maria Ilaria Del Principe, Enrico Santinelli, Idanna Innocenti, Federico Pozzo, Erika Tissino, Annalisa Biagi, Paolo de Fabritiis, Maria Cantonetti, Pietro Bulian, Sergio Amadori, Francesco Di Raimondo, Antonella Zucchetto, Valter Gattei, William Arcese
Journal: Blood (2018)
Efficacy and Safety of Ruxolitinib in Treatment of Steroid Refractory/Refractory Acute Graft-Versus-Host Disease: A Prospective Multicenter Research
Authors: Zhiping Fan, Lan Deng, Xudong Li, Qing Zhang, Li Xuan, Fen Huang, Ren Lin, Hua Jin, Na Xu, Pengcheng Shi, Zhixiang Wang, Jieyu Ye, Ling Jiang, Jing Sun, Qifa Liu
Journal: Blood (2018)
Household air pollution as an important factor in the complex relationship between altitude and COPD
Authors: Xavier Basagaña
Journal: European Respiratory Journal (2019)

The relationship between altitude and chronic obstructive pulmonary disease (COPD) remains controversial. Altitude per se is a relevant variable for respiratory health, as subjects living at high altitude are exposed to lower atmospheric pressure, which by affecting the driving pressure for gas exchange in the lungs leads to hypoxia [1]. It has been reported that high altitude natives have larger lungs and higher forced vital capacity (FVC) than predicted, potentially as an adaptation mechanism, which is relevant for COPD research, as it consequently leads to lower forced expiratory volume in 1 s to FVC ratios [2–4]. Household air pollution, whose relationship with COPD is still understudied, is yet another factor explaining the complex relationship between altitude and COPD <http://ow.ly/Ao4K30nmxDt> I thank Otavio Ranzani (ISGlobal) for critical reading of the text. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.
Neonatal salt intake and blood pressure
Authors: Atul Singhal, Tim J Cole, Alan Lucas
Journal: The Lancet (2001)

breastfed infants) extend to infants born at term, mainly because of corresponding published evidence in term infants and not primarily because our observations were independent of gestation.Third, Belton mischaracterises our views when he says that we recognise that preterm infants have greater suscptibility to later hypertension and heart disease.We wrote nothing in our paper that should have led readers to that conclusion.We recognise that low birthweight for gestation (intrauterine growth retardation) is associated with increased susceptibility to later cardiovascular disease in term and preterm babies (as stated in the discussion), but not that prematurity itself increases later cardiovascular risk.We will be publishing new data to support our view that prematurity alone is not a risk factor for later vascular disease.Belton puts words in our mouths, only to refute them.
Endoscopic resection of prepyloric diaphragm in an adult
Authors: Lin-Jie Guo, Chun-Cheng Wu, Bing Hu
Journal: Endoscopy (2019)

Prepyloric diaphragm is a rare anatomic anomaly in adults and can cause gastric outlet obstruction. A 33-year-old man presented with postprandial epigastric distress and a 10-year history of repeated nonbilious vomiting. He was otherwise healthy with no medical history of peptic ulcer or caustic ingestion. Body mass index was 15.9.
Antisense Inhibition of Glucagon Receptor by IONIS-GCGRRx Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy
Authors: Erin S. Morgan, Li-Jung Tai, Nguyen C. Pham, Julia K. Overman, Lynnetta M. Watts, Anne Smith, Shiangtung W. Jung, Martin Gajdošík, Martin Krššák, Michael Krebs, Richard S. Geary, Brenda F. Baker, Sanjay Bhanot
Journal: Diabetes Care (2019)

OBJECTIVE To evaluate the safety and efficacy of IONIS-GCGRRx, a 2′-O-methoxyethyl antisense oligonucleotide targeting the glucagon receptor (GCGR), and the underlying mechanism of liver transaminase increases in patients with type 2 diabetes on stable metformin therapy. RESEARCH DESIGN AND METHODS In three phase 2, randomized, double-blind studies, patients with type 2 diabetes on metformin received weekly subcutaneous injections of IONIS-GCGRRx (50–200 mg) or placebo for 13 or 26 weeks. RESULTS Significant reductions in HbA1c were observed after IONIS-GCGRRx treatment versus placebo at week 14 (−2.0% 200 mg, −1.4% 100 mg, −0.3% placebo; P &amp;lt; 0.001) or week 27 (−1.6% 75 mg, −0.9% 50 mg, −0.2% placebo; P &amp;lt; 0.001). Dose-dependent increases in transaminases were observed with IONIS-GCGRRx, which were attenuated at lower doses and remained mostly within the normal reference range at the 50-mg dose. There were no other significant safety observations and no symptomatic hypoglycemia or clinically relevant changes in blood pressure, LDL cholesterol, or other vital signs. At week 14, IONIS-GCGRRx 100 mg did not significantly affect mean hepatic glycogen content compared with placebo (15.1 vs. −20.2 mmol/L, respectively; P = 0.093) but significantly increased hepatic lipid content (4.2 vs. −2.7%, respectively; P = 0.005) in the presence of transaminase increases. CONCLUSIONS IONIS-GCGRRx is a potent inhibitor of hepatic glucagon receptor expression with a potential to improve glycemic control at low weekly doses in combination with metformin. Significant reductions in HbA1c occurred across the full-dose range tested, with minimal transaminase elevations at lower doses. Furthermore, novel results suggest that despite inhibition of glycogenolysis after GCGR antagonism, IONIS-GCGRRx did not increase hepatic glycogen content.
Just-in-Time Instructions for Layperson Tourniquet Application—Reply
Authors: Eric Goralnick, Justin McCarty, Adil Haider
Journal: JAMA Surgery (2019)

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Rational Targeting of a NuRD Sub-Complex for Fetal Hemoglobin Induction Following Comprehensive in Situ Mutagenesis
Authors: Mir Hossain, Falak Sher, Davide Seruggia, Vivien Schoonenberg, Mitchel A. Cole, Paolo Cifani, Laura Dassama, Claudio Macias-Trevino, Matthew C. Canver, Ryo Kurita, Yukio Nakamura, Luca Pinello, Takahiro Maeda, Alex Kentsis, Stuart H. Orkin, Daniel E. Bauer
Journal: Blood (2018)