tbuckley/cabot-search huggingface dataset:
Role of Remission Status and Prior Transplant in Optimizing Survival Outcomes Following Allogeneic Hematopoietic Stem Transplantation (HSCT) in Patients Who Received Inotuzumab Ozogamicin (INO) for Relapsed / Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)
Authors: Partow Kebriaei, Matthias Stelljes, Daniel J. DeAngelo, Nicola Goekbuget, Hagop M. Kantarjian, Anjali S. Advani, Akil Merchant, Wendy Stock, Tao Wang, Hui Zhang, Fausto Loberiza, Erik Vandendries, David Marks
Journal: Blood (2017)
LSD1 Inhibition Leads to Differentiation in Hoxa9/Meis1- but Not in MN1-Induced Acute Myeloid Leukemia
Authors: Jessica Barth, Anna-Maria Scheder, Sebastian Mohr, Johannes Schulz-Fincke, Martin Schmitt, Alexandra Walter, Milica Tosic, Eric Metzger, Gesine Bug, Michael Lübbert, Manfred Jung, Hubert Serve, Roland Schüle, Tobias Berg
Journal: Blood (2017)
Abstract 17995: Evolution of Left Ventricular Volume and Ejection Fraction in STEMI Patients: Findings From the PROMISE Randomized Clinical Trial
Authors: Ignacio Ferreira-Gonzalez, Jose Rodriguez-Palomares, Victor Pineda, Bruno Garcia-del-Blanco, Inmanol Otaegui, Alberto San-Roman, Francisco Fernandez-Aviles, Jaime Elizaga, Jose Barrabes, David Garcia-Dorado
Journal: Circulation (2016)

Introduction: Post-STEMI adverse left ventricular remodeling (AVR) is defined as an increase in end-diastolic left ventricular volume (EDLVV) without considering concomitant changes in left in vent...
A Phase 1 Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib (MLN9708) for Relapsed/ Refractory Acute Myeloid Leukemia (AML): Final Results
Authors: Anjali S. Advani, Brenda W. Cooper, Valeria Visconte, Paul Elson, E. Ricky Chan, Jennifer Carew, Sudipto Mukherjee, Aaron T. Gerds, Hetty E. Carraway, Aziz Nazha, Betty K. Hamilton, Ronald Sobecks, Paolo Caimi, Benjamin Tomlinson, Ehsan Malek, Jane A. Little, Jaime Fensterl, Allison Unger, Cassie Zimmerman, Christopher Goebel, Nita Hoxha, Caitlin Siebenaller, Jenna Thomas, Mary Lynn Rush, Samjhana Bogati, Eric Parsons, Rachael Diligente, Donna Kane, Alek Nielsen, Cassandra M. Hirsch, Simone Edelheit, Alexander Miron, John Pink, Jaroslaw P. Maciejewski, Matt Kalaycio, Marcos De Lima, Mikkael A. Sekeres
Journal: Blood (2017)
Engineering precision biomaterials for personalized medicine
Authors: Brian A. Aguado, Joseph C. Grim, Adrianne M. Rosales, Jana J. Watson-Capps, Kristi S. Anseth
Journal: Science Translational Medicine (2018)

As the demand for precision medicine continues to rise, the "one-size-fits-all" approach to designing medical devices and therapies is becoming increasingly outdated. Biomaterials have considerable potential for transforming precision medicine, but individual patient complexity often necessitates integrating multiple functions into a single device to successfully tailor personalized therapies. Here, we introduce an engineering strategy based on unit operations to provide a unified vocabulary and contextual framework to aid the design of biomaterial-based devices and accelerate their translation.
Abstract 19388: HDAC6 Inhibition Potential in Pulmonary Arterial Hypertension
Authors: François Potus, Olivier Boucherat, Sophie Chabot, Alice Bourgeois, Caroline Lambert, Sandra Breuils-Bonnet, Renée Paradis, Steeve Provencher, Sébastien Bonnet
Journal: Circulation (2016)

Introduction:  Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by the elevation of mean pulmonary arterial pressure. Pulmonary arterial smooth muscle cells (PASMCs) from PAH patients exhibit a cancer-like pro-proliferative and anti-apoptotic phenotype leading to development of progressive pulmonary artery remodeling. The histone deacetylase 6 (HDAC6) is mainly cytoplasmic and involved primarily in “non-histone” functions. Previous studies have shown that HDAC6 plays critical roles on many cellular processes related to cancer.   Hypothesis:  HDAC6 inhibition corrects the abnormal phenotype of PAH-PASMCs and improves PAH.   Methods and Results:  Using a multidisciplinary and translational approach, we demonstrated that HDAC6 is upregulated (WB; p In vitro , inhibition of HDAC6 increases DNA damage (γH2AX, WB) and promotes the accumulation of ubiquitinated protein aggregates potentially toxic for the cell (ubiquitin, WB and IF). Finally, in both monocrotaline and sugen/hypoxia rat models of PAH, we demonstrated that HDAC6 inhibition using Tubastatin A (25mg/kg/day, 14 days, i.p.) improves pulmonary hemodynamic (p   Conclusions:  We provide evidence that HDAC6 is upregulated in human PAH and contribute to the proliferative and anti-apoptotic phenotype of PAH-PASMCs. HDAC6 inhibition may represent a novel and attractive avenue for reversing PAH avoiding the adverse off-target effects of pan-HDAC inhibitors. The susceptibility of HDAC6 KO mice to develop PAH following hypoxia exposure is currently under investigation.
IL33 Receptor Deficiency Leads To Steroid Resistant Asthma Due To TSLP-driven Increase In IL9+ILC2s And Mast Cells
Authors: Mukesh Verma, Sucai Liu, Lidia Michalec, Anand Sripada, Magdalena M. Gorska, Rafeul Alam
Journal: Journal of Allergy and Clinical Immunology (2018)
Sleeve gastrectomy matches gastric bypass in terms of weight loss and health benefits
Authors: Jacqui Wise
Journal: BMJ (2018)

Sleeve gastrectomy and gastric bypass are overall fairly similar in terms of their effects on weight and comorbid conditions, according to three studies in a special obesity theme issue of JAMA .

Over the past decade, sleeve gastrectomy has replaced the Roux-en-Y gastric bypass as the procedure of choice in the management of patients with severe obesity. Sleeve gastrectomy—where a part of the stomach is removed—is a technically easier operation than the bypass procedure; however, there are less long term data supporting its use.

A large retrospective study shows that patients who underwent bariatric surgery had a lower rate of death from any cause over four years than patients who managed …
Abstract 16184: Elevated Maternal Glucose Levels During Gestation may Confer Specific Risk for Tetralogy of Fallot
Authors: James R Priest, Wei Yang, Gerald Reaven, Joshua W Knowles, Gary M Shaw
Journal: Circulation (2015)

Introduction: Clinicians have long observed an association between maternal diabetes and risk of congenital heart disease (CHD) in offspring. Though the clinical diagnoses of Type 2 diabetes or gestational diabetes are strong maternal risk factors, this diagnostic classification captures only a subset of patients with overt hyperglycemia not more subtle abnormalities of glucose or insulin metabolism. We explored the potential risk for two different CHD phenotypes in offspring with with midpregnancy measures of glucose, insulin, and insulin resistance. Hypothesis: We hypothesize that continuous measures of blood analytes related to maternal diabetes will be associated with the risk for two CHD phenotypes tetralogy of Fallot (ToF) and d-Transposition of the Great Arteries (dTGA) which have been recently associated with overt diabetes. Methods: We assembled a prospective cohort of 277 women carrying infants with ToF (n=55), dTGA (n=42), or nonmalformed control infants without CHD (n=180), and measured serum insulin by a validated radioimmunoassay and glucose levels in second trimester blood samples. We performed univariable as well as multivariable analyses to investigate statistical associations. Results: Maternal glucose levels were associated with elevated risk for both CHD phenotypes in offspring with an adjusted odds ratio (OR) of 6.61 (95%CI 1.67-26.13), which in subgroup analysis was driven by a strong association with ToF (OR 18.45, 95%CI 3.34-102.08) compared to the much lower OR for dTGA (OR 1.24, 95%CI 0.16-9.59). Conclusions: We observed that maternal blood glucose levels are strongly associated with risk for ToF, which is consistent with recent epidemiological data. These results represent the first direct correlation of glucose as a continuous variable to risk for specific cardiac malformations. In conclusion the association between serum glucose and risk for ToF suggest the need for additional epidemiological and mechanistic investigations into the risk for conferred by insulin signaling and glucose metabolism during early pregnancy.
Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion
Authors: Carlo Spreafico, Carlo Sposito, Marta Vaiani, Tommaso Cascella, Sherrie Bhoori, Carlo Morosi, Rodolfo Lanocita, Raffaele Romito, Carlo Chiesa, Marco Maccauro, Alfonso Marchianò, Vincenzo Mazzaferro
Journal: Journal of Hepatology (2018)
Erratum: Corrigendum: PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells
Authors: Shiri Gur-Cohen, Tomer Itkin, Sagarika Chakrabarty, Claudine Graf, Orit Kollet, Aya Ludin, Karin Golan, Alexander Kalinkovich, Guy Ledergor, Eitan Wong, Elisabeth Niemeyer, Ziv Porat, Ayelet Erez, Irit Sagi, Charles T Esmon, Wolfram Ruf, Tsvee Lapidot
Journal: Nature Medicine (2016)
Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases
Authors: N.C. Turner, R.S. Finn, M. Martin, S.-A. Im, A. DeMichele, J. Ettl, V. Diéras, S. Moulder, O. Lipatov, M. Colleoni, M. Cristofanilli, D.R. Lu, A. Mori, C. Giorgetti, S. Iyer, C. Huang Bartlett, K.A. Gelmon
Journal: Annals of Oncology (2018)

BackgroundThis report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases.Patients and methodsPre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N= 521) and postmenopausal women untreated for ABC (PALOMA-2; N= 666) were randomized 2:1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement.ResultsVisceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35–0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36–0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47–0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36–0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC.ConclusionsPalbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy.Clinical trial registrationNCT01942135, NCT01740427
Microfluidic Tumor–Vascular Model to Study Breast Cancer Cell Invasion and Intravasation
Authors: Supriya Nagaraju, Danh Truong, Ghassan Mouneimne, Mehdi Nikkhah
Journal: Advanced Healthcare Materials (2018)

Abstract Cancer is a major leading cause of disease‐related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment. To that end, in this work, a novel 3D microfluidic platform comprised of concentric three‐layer cell‐laden hydrogels for simultaneous investigation of breast cancer cell invasion and intravasation as well as vasculature maturation influenced by tumor–vascular crosstalk is developed. It was demonstrated that the presence of spontaneously formed vasculature enhance MDA‐MB‐231 invasion into the 3D stroma. Following invasion, cancer cells are visualized intravasating into the outer vasculature. Additionally, invading cancer cells significantly reduce vessel diameter while increasing permeability, consistent with previous in vivo studies. Major signaling cytokines involved in tumor–vascular crosstalk that govern cancer cell invasion and intravasation are further identified. Taken together, this platform will enable unique insights of critical biological events within the metastatic cascade, with significant potential for developing efficient cancer therapeutics.
Abstract 15274: Determinants of Exercise Tolerance After Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Sunao Miyanaga, Kayoko Kubota, Noriko Iwatani, Kenjuro Higo, Yoshihisa Horizoe, Hideto Chaen, Nami Uchiyama, Satoko Ojima, Shin Kawasoe, Takurou Kubozono, Masaaki Miyata, Mitsuru Ohishi
Journal: Circulation (2016)

Introduction:  In patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), balloon pulmonary angioplasty (BPA) has become an alternative therapy to improve hemodynamics, right ventricular (RV) function and exercise intolerance. Exercise intolerance, a key feature of CTEPH, remains even after BPA. However, the determinants of exercise capacity after BPA in patients with CTEPH have not been elucidated. The purpose of this study was to identify the determinants after BPA in patients with CTEPH.   Method:  We analyzed the consecutive 9 patients with CTEPH who underwent BPA. Six months after their final session of BPA, respiratory function test was performed at rest. In addition, we performed right heart catheterization, cardiopulmonary exercise test, and echocardiography simultaneously to observe hemodynamics and respiratory change during exercise by ergometer at supine position. As the indices of RV function, we used tricuspid annular plane systolic excursion (TAPSE) and RV-S’ using tissue Doppler imaging by echocardiography.   Result:  The median age was 73.0 (25%, 75%: 68.5, 76.0) years old. The median peak VO2/kg was 15.1 (14.1, 16.9) ml/min/kg, median mean pulmonary artery pressure (mPAP) increased from 22.0 (18.0, 23.5) mmHg at rest to 54.0 (47.5, 62.5) mmHg at peak and PVR also increased from 268 (294, 407) dynes s cm -5  at rest to 361 (255, 515) dynes s cm -5  at peak. The peak VO2/kg significantly correlated with PVR at peak (Figure A: R=-0.70, P=0.033), delta mPA / delta cardiac output (B: R=-0.80, P=0.008), rest PvO2 (C: R=0.69, P=0.039) and %VC (D: R=0.81, P=0.008). In contrast, there was no significant association between peak VO2/kg and left ventricular ejection fraction, brain natriuretic peptide, TAPSE, RV-S’, cardiac output or hemoglobin levels.   Conclusion:  We for the first time found that the exercise tolerance was determined by the hemodynamics and respiratory function, but not cardiac function, in patients with CTEPH after BPA.
Book: Moments of Truth: Four Creators of Modern Medicine
Authors: Ioana Vlad
Journal: BMJ (2004)

None of the four 19th century medical personalities who are the subjects of this book won the Nobel prize, but all made important steps in the development of today's medicine. At a time when immediate auscultation and hippocratic succusion (holding patients by their shoulders and shaking them vigorously) were typical diagnostic procedures, the Frenchman Rene Laennec invented the stethoscope and introduced it to clinical practice. Ignaz Semmelweis, a Hungarian obstetrician, proved that puerperal fever was a type of septicaemia and pioneered antiseptic obstetrics. The book's third part focuses on the more famous pioneer of antisepsis, Joseph Lister, and the fourth on Walter Reed, the US army pathologist who discovered that yellow fever was spread by mosquitoes.​mosquitoes.




Figure 1



Thomas Dormandy

John Wiley, £18.99/$30, pp 563 ISBN 0 470 86321 8

Rating: ★★★




The author, a retired consultant pathologist, describes the historical difficulties that the four men faced. Laennec, born in 1781, lived through four decades of political turbulence in France. During the First Republic privileges and social distinctions were disregarded and “anybody could call himself a doctor and practise medicine,” resulting in a dramatic rise in mortality and morbidity. However, later, under Napoleon, medical education was developed and governing bodies re-established, allowing Laennec to pursue his scientifically based medical career. Semmelweis practised in Habsburg Vienna and as a Hungarian was criticised by his local colleagues. Lister's use of carbolic acid as an antiseptic brought derision from his fellow practitioners and students. Walter Reed had to pursue his career as an army doctor at a time of military conquest against Native Americans.

Dormandy skilfully interweaves the work of the four men with the academic, political, and medical intrigues of their time. Scientific fraud and competing political and financial interests were as much a part of the 19th century as they are of our own times. More generally, the book also beautifully describes life at peace and at war in revolutionary and Napoleonic France, imperial Austria, Victorian England, and late 19th and early 20th century America. However, despite a thorough notes section at the end of the book giving even more historical detail, Dormandy includes too many descriptive details, making it a little difficult to follow the lives of the main characters.

All four figures were crucial to the evolution of medicine from a practice of charlatans and skilled barbers to a profession based on science. Maybe in 100 years' time another author will write a similar book on the development of today's evidence based medicine. But are equivalent discoveries possible today? Would any famous medical journal publish the work of one clinician that wasn't a randomised controlled trial and that lacked enough participants to have statistical significance?
Time for a longer and better life for patients with COPD
Authors: Lowie E.G.W. Vanfleteren, Anders Ullman, Leonardo M. Fabbri
Journal: European Respiratory Journal (2018)

Together with the adequate delivery of the right drugs to the right patient at the right dosage, and aimed at the right outcomes, the most important management goals in patients with chronic obstructive pulmonary disease (COPD) are the following: smoking abstinence, physical activity and a balanced diet; adhering to complex medication regimens; and developing the ability to recognise signs and symptoms of deterioration, and knowing what to do to prevent or reverse them [1]. Managed care may reduce mortality in severe COPD patients with previous hospitalisation <http://ow.ly/THpI30hiaYJ>
Efficacy of anti-CTLA-4 antibody in the SA1N tumor model when combined with dexamethasone
Authors: Bingliang Chen, James Phillips, Meghan Greenbaum, David Klitzing, Pina Cardarelli, Alan Korman
Journal: Cancer Research (2007)

2202  CTLA-4 is a negative costimulatory molecule expressed by multiple T cell subsets. Inhibition CTLA-4 activity by monoclonal antibodies has been shown to enhance anti-tumor responses in a variety of murine models. Ipilimumab (MDX-010; BMS-734016), a human antibody against CTLA-4, has shown activity against multiple f tumor types in clinical trials. Anti-cancer responses have been frequently associated with inflammatory adverse events that are suggestive of T cell activation, such as colitis, rash, and hypopituitarism. Serious adverse events are managed by cessation of antibody and the use immunosuppressive doses of corticosteroids, while durable anti-tumor responses have been maintained. Using a murine Sa1N fibrosarcoma model sensitive to anti-CTLA-4 monotherapy, the effect of dexamethasone (Dex) on anti-tumor activity was investigated. Sa1N cells were implanted in A/J mice and treated at ~100 mm3 with an anti-CTLA-4 antibody (9D9, 10 mg/kg), Q3Dx4. Dex (1 or 10 mg/kg; Q2Dx7) was initiated 7 days after anti-CTLA-4 treatment. In two separate experiments (example below), anti-CTLA-4 resulted in 85% and 97% mean tumor growth inhibition (TGI). Delayed treatment with Dex at 1 mg/kg did not effect TGI mediated by anti-CTLA-4 (83% and 95% TGI), while Dex at 10 mg/kg resulted in a limited abrogation of the anti-tumor effect (78% and 91% TGI). When Dex (1 and 10 mg/kg) was given concurrently with anti-CTLA4 (5 mg/kg), the anti-tumor effect by anti-CTLA-4 was still retained at early time points (day 18) but ultimately resulted in a reversal of TGI and tumor outgrowth at 24 days. Dex treatment alone did not significantly effect tumor volume in any study. These data support the use of corticosteroids in the treatment of adverse events following anti-CTLA-4 immunotherapy.
Association and birth prevalence of microcephaly attributable to Zika virus infection among infants in Paraíba, Brazil, in 2015–16: a case-control study
Authors: Elisabeth R Krow-Lucal, Marcia Regina de Andrade, Juliana Nunes Abath Cananéa, Cynthia A Moore, Priscila Leal Leite, Brad J Biggerstaff, Cibelle Mendes Cabral, Megumi Itoh, Jadher Percio, Marcelo Y Wada, Ann M Powers, Aristides Barbosa, Roberta Batista Abath, J Erin Staples, Giovanini Evelim Coelho, Emerson Araújo, Eva Lídia Arcoverde Medeiros, Jonas Brant, Matheus Cerroni, Henrique de Barros Moreira Beltrão, Francieli Fontana Sutile Tardetti Fantinato, Michael Laurence Zini Lise, Patrícia Miyuki Ohara, Elionardo Resende, Eduardo Saad, Annabelle de St. Maurice, Ada Dieke, Alexia Harrist, Natalie Kwit, Mariel Marlow, Gnakub Soke, Roseanne de Arruda Pessoa, Renata Candido da Silva, Rogéria Chelly Diniz, Micheline César de Araújo Ariette, Clarice França Lira, Sandra Matos, Taciana Mendonça Maia Wanderley, Vanessa Oliveira Costa Silva, Hélio Soares da Silva, Eduardo Hage Carmo, Myrian Carvalho, Nena Lentini, Raquel Miranda, Erin Boland, Paul Burns, Marc Fischer, Jeremy Ledermann, Fatima Coronado, Julio Dicent-Taillepierre, Brendan Flannery, Alexandre Macedo de Oliveira, José Fernando Arena
Journal: The Lancet Child & Adolescent Health (2018)
Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial
Authors: Bernadette Li, Alec Miners, Haleema Shakur, Ian Roberts
Journal: The Lancet Global Health (2018)

Sub-Saharan Africa and southern Asia account for almost 85% of global maternal deaths from post-partum haemorrhage. Early administration of tranexamic acid, within 3 h of giving birth, was shown to reduce the risk of death due to bleeding in women with post-partum haemorrhage in the World Maternal Antifibrinolytic (WOMAN) trial. We aimed to assess the cost-effectiveness of early administration of tranexamic acid for treatment of post-partum haemorrhage.
Ibrutinib Is Highly Active As First Line Therapy in Symptomatic Waldenstrom's Macroglobulinemia
Authors: Steven P Treon, Joshua Gustine, Kirsten Meid, Toni Dubeau, Patricia Severns, Christopher Patterson, Lian Xu, Guang Yang, Xia Liu, Maria Demos, Amanda Kofides, Jiaji Chen, Manit Munshi, Nickolas Tsakmaklis, Gloria Chan, Andrew J Yee, Noopur Raje, Elizabeth O'Donnell, Zachary Hunter, Jorge J. Castillo
Journal: Blood (2017)