tbuckley/cabot-search huggingface dataset:
Long-Term Outcome of Children with Acute Myeloid Leukemia in First Remission Given Allogeneic HSCT from a Matched Family Donor After a Conditioning Regimen Comprising Busulfan, Cyclophosphamide and Melphalan.
Authors: Marco Zecca, Riccardo Masetti, Adriana Balduzzi, Franca Fagioli, Giorgio Dini, Chiara Messina, Attilio Rovelli, Luca Lo Nigro, Mario Regazzi, Giuseppe Basso, Andrea Pession, Arcangelo Prete, Franco Locatelli
Journal: Blood (2009)
Role of PET/CT in the Diagnostic Work-up of Patients with Chronic Lymphocytic Leukemia (CLL) and Clinical Signs of Disease Progression
Authors: Francesca R Mauro, Mara Riminucci, Davide Rossi, Francesca Paoloni, Luca Laurenti, Anna M Frustaci, Giuseppe Cimino, Michelina Santopietro, Chiara Spadafora, Angela Rago, Francesco Autore, Molica Matteo, Brocchieri Simonetta, Emanuele Nicolai, Gianluca Gaidano, Anna Guarini, Bianco Paolo, Robin Foà
Journal: Blood (2012)
The Expressions of CD114, CD117 and STAT5 in CD34+CD59− and CD34+CD59+ Bone Marrow Cells of the Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Rong Fu, Shaoxue Ding, Zonghong Shao, Lijuan Li, Hui Liu, Honglei Wang, Tian Zhang
Journal: Blood (2012)
Antifungal Prophylaxis with Posaconazole in Allogeneic Hematopoietic Stem Cell Transplantation Using Sirolimus for Prevention of Graft-Versus-Host Disease
Authors: Raffaella Greco, Maria Chiara Barbanti, Alessandra Forcina, Maria Teresa Lupo Stanghellini, Fabio Giglio, Mara Morelli, Luca Vago, Simona Piemontese, Carlo Messina, Elisa Sala, Francesca Pavesi, Sarah Marktel, Matteo G Carrabba, Andrea Assanelli, Massimo Bernardi, Jacopo Peccatori, Consuelo Corti, Fabio Ciceri
Journal: Blood (2015)
Sequence specific effects on DNA and cell damage with the PARP inhibitor olaparib (AZD2281) and carboplatin.
Authors: J. L. Hays, G. Kim, J. Mariani, R. F. Murphy, M. Angelos, A. McCollum, J. Lu, B. C. Widemann, J. Lee, E. C. Kohn
Journal: Journal of Clinical Oncology (2011)

5025 Background: We have found clinical activity of carboplatin (C) with the PARP inhibitor olaparib (O) in BRCA1/2mut or BRCA-like breast and ovarian cancers. Current clinical trials are testing the hypothesis that PARP inhibition will sensitize tumors to platinum agents. We have examined sequence specificity of C and O combinations in cell lines, including two BRCA1mut (HCC1937, UWB1.289) and two BRCA-WT lines (OVCAR8, HeyA8), on the development of DNA damage and cell injury. Methods: Cell injury was measured with XTT assays. DNA damage was examined using Comet assay with tail quantification and γH2AX foci by immunofluorescence. Platinum DNA-adduct formation was measured using atomic absorption spectrometry and normalized to DNA input. Results: Exposure to O prior to C for 24 hours (O>C) reduced the efficiency of double stranded DNA damage compared to C alone or O+C (p<0.05 for O>C vs. C or O+C) measured by γH2AX foci/nucleus in BRCA1mut cell lines, UWB1.289: 11.0 (O>C), 40.9 (C), 46.4 (O+C); HCC1937: 14.7 (O>C), 53.2 (C), 60.6 (O+C). This trend was not observed in BRCA-WT cell lines. Comet assay demonstrated decreased DNA damage as a reduced percentage of DNA in the comet tail in BRCA1mut cells treated with O>C compared to C (p<0.05) but not O+C (p=not significant), HCC1937: 11.3% (C), 3.4% (O>C), 5.1% (O+C); UWB1.289: 7.3% (C), 2.4% (O>C), 5.1% (O+C). Cell cytotoxicity by XTT assay indicated O>C had decreased cytotoxic effects compared to C or O+C (p<0.05 for O>C vs. C or O+C) in BRCA1mut cell lines, UWB1.289: 69% (O>C), 44% (C), 40% (O+C); HCC1937: 88% (O>C), 68% (C), 63% (O+C). Platinum adduct formation was not affected by treatment with O in either BRCA1mut cell lines or BRCA-WT cell lines. Conclusions: The sequencing of O with C yields changes in cytotoxicity and the quantity of DNA damage observed in both comet analysis and γH2AX focus formation while platinum adducts were not altered by O exposure. This suggests pretreatment of BRCA-deficient cell lines with PARP inhibition may up-regulate other DNA repair pathways and lead to paradoxically less DNA damage than seen with C alone or C+O concurrently. Further studies are ongoing to evaluate this question.
Bortezomib-Bendamustine-Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (MM) Shows Marked Efficacy and Is Well Tolerated, but Assessment of PNP Symptoms Shows Significant Discrepancies Between Patients and Physicians
Authors: Heinz Ludwig, Hedwig Kasparu, Werner Linkesch, Josef Thaler, Richard Greil, Clemens Leitgeb, Daniel Heintel, Elisabeth Rauch, Niklas Zojer, Ludek Pour, Adelheid Seebacher, Zdenek Adam
Journal: Blood (2011)
EXHANCE-3: A Phase 3, Three-Month Study of Safety and Efficacy of Fluticasone Propionate Exhalation Delivery System (FLU-EDS) in Patients with Chronic Rhinosinusitis with (CRSwNP) and without Nasal Polyps (CRSsNP)
Authors: Mandel R. Sher, Eric A. Mair, John Messina, Jennifer Carothers, Ramy Mahmoud, Per G. Djupesland
Journal: Journal of Allergy and Clinical Immunology (2017)
Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2
Authors: Brandon C. Sos, Charles Harris, Sarah M. Nordstrom, Jennifer L. Tran, Mercedesz Balázs, Patrick Caplazi, Maria Febbraio, Milana A.B. Applegate, Kay-Uwe Wagner, Ethan J. Weiss
Journal: Journal of Clinical Investigation (2011)
A novel biased antagonist of the eotaxin-CCR3 pathway in eosinophils
Authors: Milica M. Grozdanovic, Lee K. Rousslang, Hazem Abdelkarim, Kimberly G. Laffey, Ben Hitchinson, Nadya Tarasova, Vadim Gaponenko, Steven J. Ackerman
Journal: Journal of Allergy and Clinical Immunology (2017)
Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association
Authors: Amish N. Raval, Joaquin E. Cigarroa, Mina K. Chung, Larry J. Diaz-Sandoval, Deborah Diercks, Jonathan P. Piccini, Hee Soo Jung, Jeffrey B. Washam, Babu G. Welch, Allyson R. Zazulia, Sean P. Collins
Journal: Circulation (2017)

Non–vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.
Protean proteases: at the cutting edge of lung diseases
Authors: Clifford Taggart, Marcus A. Mall, Gilles Lalmanach, Didier Cataldo, Andreas Ludwig, Sabina Janciauskiene, Nicole Heath, Silke Meiners, Christopher M. Overall, Carsten Schultz, Boris Turk, Keren S. Borensztajn
Journal: European Respiratory Journal (2017)

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web. In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases. The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies. Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.
Successful Translation of Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Cell Processing Technology from Academia to Industry
Authors: Jeffrey A. Boyd, Bruce L. Levine, Kathrin Jinivizian, Margit A. Jeschke, Megan M. Suhoski Davis, Zhaohui Zheng, Daniel Stark, Liza Loidolt, Christopher H. Keir, Patricia A. Wood
Journal: Blood (2015)
Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder
Authors: Noa Lipstein, Nanda M. Verhoeven-Duif, Francesco E. Michelassi, Nathaniel Calloway, Peter M. van Hasselt, Katarzyna Pienkowska, Gijs van Haaften, Mieke M. van Haelst, Ron van Empelen, Inge Cuppen, Heleen C. van Teeseling, Annemieke M.V. Evelein, Jacob A. Vorstman, Sven Thoms, Olaf Jahn, Karen J. Duran, Glen R. Monroe, Timothy A. Ryan, Holger Taschenberger, Jeremy S. Dittman, Jeong-Seop Rhee, Gepke Visser, Judith J. Jans, Nils Brose
Journal: Journal of Clinical Investigation (2017)

Munc13 proteins are essential regulators of neurotransmitter release at nerve cell synapses. They mediate the priming step that renders synaptic vesicles fusion-competent, and their genetic elimination causes a complete block of synaptic transmission. Here we have described a patient displaying a disorder characterized by a dyskinetic movement disorder, developmental delay, and autism. Using whole-exome sequencing, we have shown that this condition is associated with a rare, de novo Pro814Leu variant in the major human Munc13 paralog UNC13A (also known as Munc13-1). Electrophysiological studies in murine neuronal cultures and functional analyses in Caenorhabditis elegans revealed that the UNC13A variant causes a distinct dominant gain of function that is characterized by increased fusion propensity of synaptic vesicles, which leads to increased initial synaptic vesicle release probability and abnormal short-term synaptic plasticity. Our study underscores the critical importance of fine-tuned presynaptic control in normal brain function. Further, it adds the neuronal Munc13 proteins and the synaptic vesicle priming process that they control to the known etiological mechanisms of psychiatric and neurological synaptopathies.
GENT-37. THE GENETICS DRIVING RADIATION INDUCED MENINGIOMAS
Authors: Peter Tonge, Sameer Agnihotri, Shahrzad Jalali, Arnavaz Danesh, Jeff Bruce, Trevor Pugh, Ken Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2016)

One-third of all primary central nervous system tumors in adults are meningiomas, which arise from the meninges. Although the majority of meningioma cases are not associated with an environmental risk factor, it is well established that individuals receiving radiation treatment to the CNS are susceptible to radiation-induced meningiomas. The genomic integrity of spontaneous meningiomas has been extensively profiled by whole genome sequencing and exome sequencing, providing a well-developed catalogue of meningioma associated mutations. In contrast, a comprehensive understanding of the molecular changes associated with RIMs is undetermined. We have compiled a cohort of radiation-induced meningiomas and molecularly characterized their methylome, transcriptome and mutational signatures. The integration of these three platforms at base-pair resolution has facilitated the identification of molecular changes that drive oncogenesis. We reveal that radiation induced meningiomas possess a unique mutational signature that is distinct from spontaneous meningiomas. This distinct mutational signature is dominated by genomic rearrangements that generate novel fusion genes and disrupt tumor suppressors. These findings have serious implications for the development of therapies focused towards the treatment of radiation-induced meningiomas. In summary, this is the largest cohort of profiled meningiomas to date, providing a robust characterization of distinct radiation induced meningioma features that can be exploited for the development of future therapies.
Massively Parallel Mate Pair DNA Library Sequencing for Translocation Discovery: Recurrent t(6;7)(p25.3;q32.3) Translocations In ALK-Negative Anaplastic Large Cell Lymphomas
Authors: Andrew L Feldman, Ahmet Dogan, David I Smith, Mark E Law, Stephen M. Ansell, Sarah H Johnson, Julie C Porcher, Nazan Özsan, Eric D Wieben, Bruce W Eckloff, George Vasmatzis
Journal: Blood (2010)
DISCRIMINATION BETWEEN CRIGLER-NAJJAR TYPE-I AND TYPE-II BY EXPRESSION OF MUTANT BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE
Authors: J Seppen, Bg Goldhoorn, Ctm Bakker, [No Value] Chowdhury, Nr Chowdhury, Plm Jansen, Rpjq Elferink
Journal: Hepatology (1994)
Significance of the hedgehog (Hh) pathway in ovarian cancer xenograft growth.
Authors: B. R. Rueda, C. McCann, W. B. Growdon, R. Foster, M. D. Curley, R. W. Ross, J. Proctor, J. MacDougall
Journal: Journal of Clinical Oncology (2010)

5058 Background: Initial immunohistochemical analysis revealed that about 50% of ovarian cancer samples expressed sonic Hh ligand in the tumor epithelium, suggesting this signaling pathway might be active in this disease. Thus we examined the activity of IPI-926, a potent inhibitor of the Hh pathway that blocks the activity of Smoothend, in a preclinical model of serous ovarian cancer in an adjuvant and maintenance setting. Methods: Primary human serous ovarian tumor xenograft tissue was utilized to generate tumor explants in NOD/SCID mice. Mice bearing tumors (250-1900 mm3) were randomized into four groups 1) IPI-926 PO gavage q 24 hours along with intraperitoneal (IP) vehicle; 2) paclitaxel and carboplatinum (T/C) IP q 7 days with vehicle by PO gavage q 24 hours; 3) IPI-926 by PO gavage q 24 hours + IP T/C; 4) vehicle by PO gavage q 24 hours + IP vehicle q 7 days. The adjuvant treatment period spanned 19 days. In the maintenance arms of the experiment, T/C treatment was stopped in the two groups receiving T/C. These mice continued to receive vehicle or IPI-926 for 24 days. Tumor volume and mouse weights were regularly assessed in experiments. Mouse and human Gli1 were assessed in tumor explants by RT PCR 24 hours after treatment with IPI-926 or vehicle. Results: In the adjuvant setting, IPI-926 inhibited growth compared to vehicle (p = 0.006). Weight loss was similar for all groups. In the maintenance experiment, continued treatment with IPI-926 further inhibited tumor growth when compared to vehicle. Continued treatment with IPI-926 was required to maintain efficacy. There was a 1,000-fold inhibition of Gli1 expression in the tumor associated stroma when compared to vehicle (p < 0.0002) 24 hours post treatment with IPI-926. This modulation was not seen in the tumor cells. Conclusions: IPI-926 treatment precludes tumor growth in the adjuvant and maintenance therapy setting suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may be useful as targeted therapy. The modulation of Gli1 expression in the stromal compartment implies signaling between the tumor and stroma. These data suggest that therapeutic inhibition of the Hh pathway could be an important strategy to extend progression-free survival in ovarian cancer patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Infinity Infinity Infinity
Effectiveness of Decitabine in Chronic Myelomonocytic Leukemia Patients. International Cooperative Multi-Center Study.
Authors: Marcelo Iastrebner, Jun Ho Jang, Isolda Fernandez, Kihyun Kim, Guy Garay, Dong Hwan (Dennis) Kim, Silvia Saba, Chul Won Jung, Fernando Santini, Haydee i Bernard, Lino Salvatierra, Jorge Korin, Gustavo Taborda, Ricardo Antonio Giuliani, Gabriela Flores, Alejandro Flores
Journal: Blood (2009)
Relevance of α-Globin Genotyping in Patients Expressing HbH in Cord Blood: Prevalence of α-Globin Gene Deletions and α2-Globin Termination Codon Mutations in a Neonatal Hemoglobinopathy Screening Program
Authors: Vincent-Philippe Lavallée, Denis Soulieres, Xiaoduan Weng, Louise Robin, Steven Girard, Gilbert Cornut, Marie-Lise Audette
Journal: Blood (2008)
100P Phase III of study of docetaxel and carboplatin with or without doxorubicin hydrochloride and cyclophosphamide in treating women with triple negative breast cancer
Authors: S. Najafi, M. Payandeh, M. Sadeghi, F. Zahra Shojaiyan, F. Abbasvandi, V. Shafahi
Journal: Annals of Oncology (2016)
Plasticity of tumor associated macrophages in a metastatic melanoma model in the mouse
Authors: Annamaria Gal, Thomas Tapmeier, Ruth Muschel
Journal: Cancer Research (2012)

Macrophages acquire different functional traits, with the pro-inflammatory, classically activated M1 and the tissue-repair, alternatively activated M2 phenotypes the best characterized to date. Tumor-associated macrophages (TAMs) have been described as alternatively activated and exert pro-tumoral activity. We investigated TAMs isolated from subcutaneous tumors and experimental lung metastases at an early (72 h) and late (3 wk) stage within a B16F10 mouse melanoma model. The macrophages were characterized according to their expression of genes, surface markers and secreted factors. Interestingly, the mRNA profile revealed both M1- and M2-associated gene expression in macrophages derived from s.c. melanoma, including Cxcl9, Cxcl11, Il-1a, Nos2, and Retnla (FIZZ-1), Arg-1 and Fn1, respectively. In early pulmonary metastases, we found that macrophages also expressed both pro-inflammatory (Il1b, Il12b, Ccl2), and anti-inflammatory (Ccl17 and Ccl22) cytokines and chemokines and other M1- and M2-associated genes, such as Cd40, Cd86, and Il27ra and Itgax (Cdd11c), respectively. Macrophages from late stage lung metastases displayed predominantly alternatively activated characteristics with Arg1, Retnla and Fn1 expression, but pro-inflammatory genes, such as Ccl2, Il1b and Cxcl10 were also induced/upregulated. We therefore suggest an intermediate phenotype of TAMs which does not fit the orthodox M1/M2 paradigm. To describe the mechanism by which macrophages are recruited to pulmonary metastases, we investigated chemokine receptor expression of macrophages infiltrating the lung. While Ccr2 was expressed at high level in macrophages associated with both the control and B16F10 metastases bearing lung, we found that Ccr1 and Ccr5 expression was induced after tumor cell challenge. The secretion profile of B16F10 cells revealed CCL5 (RANTES), a ligand for these receptors, secreted at high level, which suggests that CCL5 attracts macrophages to lung metastases via CCR1 and CCR5. The effect of anti-CCL5 antibody treatment, and s.c melanoma growth and pulmonary metastasis development in CCR1-/- and CCR5-/- mice will be discussed.
Sixty seconds on . . . medical school applications
Authors: Tom Moberly
Journal: BMJ (2017)

Indeed. Making a difference, wanting to care, lifelong ambition, and all that.

Exactly. But even starry eyed A level students are thinking twice these days before signing up to a life of clerking patients, tracking down available beds, and arguing with health service managers.

It is. Last year there were nine plucky applicants fighting over every place on offer, but there’s been a …
Conditional Deletion of Asxl1 Results in Myelodysplasia
Authors: Omar Abdel-Wahab, Jie Gao, Mazhar Adli, Young Rock Chung, Richard Koche, Alan H. Shih, Suveg Pandey, Lindsay M. La-Fave, Delphine Ndiaye-Lobry, Yu Sup Shin, Parva K. Bhatt, Jay P. Patel, Xinyang Zhao, Christopher Y. Park, Jacob D. Jaffe, Bradley E. Bernstein, Iannis Aifantis, Ross L. Levine
Journal: Blood (2012)
Sirolimus and Post Transplant Cyclophosphamide (PT-Cy) Allow the Use of Haploidentical PBSC Grafts Inducing a Favorable Immune Reconstitution with Low Rates of GvHD: Results in 39 Patients
Authors: Nicoletta Cieri, Raffaella Greco, Lara Crucitti, Mara Morelli, Fabio Giglio, Giorgia Levati, Andrea Assanelli, Francesca Lorentino, Maria Teresa Lupo Stanghellini, Luca Vago, Tiago Freitas, Sarah Marktel, Massimo Bernardi, Consuelo Corti, Chiara Bonini, Fabio Ciceri, Jacopo Peccatori
Journal: Blood (2014)
Identification of CD20 Mutations in Malignant Lymphoma: Can They Be Predictors of Response to Rituximab?.
Authors: Yasuhito Terui, Takuma Sakurai, Yuji Mishima, Yuko Mishima, Natsuhiko Sugimura, Kiyotsugu Kojima, Masahiro Yokoyama, Kiyohiko Hatake
Journal: Blood (2005)
Dietary fiber and prebiotics and the gastrointestinal microbiota
Authors: Hannah D. Holscher
Journal: Gut Microbes (2017)

The gastrointestinal microbiota has an important role in human health, and there is increasing interest in utilizing dietary approaches to modulate the composition and metabolic function of the microbial communities that colonize the gastrointestinal tract to improve health, and prevent or treat disease. One dietary strategy for modulating the microbiota is consumption of dietary fiber and prebiotics that can be metabolized by microbes in the gastrointestinal tract. Human alimentary enzymes are not able to digest most complex carbohydrates and plant polysaccharides. Instead, these polysaccharides are metabolized by microbes which generate short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. This article reviews the current knowledge of the impact of fiber and prebiotic consumption on the composition and metabolic function of the human gastrointestinal microbiota, including the effects of physiochemical properties of complex carbohydrates, adequate intake and treatment dosages, and the phenotypic responses related to the composition of the human microbiota.