tbuckley/cabot-search huggingface dataset:
Daunorubicin, Cytarabine and Fludarabine (DAF) for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Phase II Study by the Polish Adult Leukemia Group (PALG).
Authors: Jerzy Holowiecki, Sebastian Grosicki, Slawomira Krzemien, Aleksander Skotnicki, Krzysztof Warzecha, Barbara Zdziarska, Beata Stella-Holowiecka, Malgorzata Krawczyk-Kulis, Malgorzata Kopera, Maria Wojciechowska
Journal: Blood (2004)
Hemostatic Effect of a Novel Bispecific Antibody (ACE910) Against Activated Factor IX and Factor X in an Acquired Hemophilia A Model
Authors: Atsushi Muto, Takehisa Kitazawa, Kazutaka Yoshihasi, Minako Takeda, Tetsuhiro Soeda, Tomoyuki Igawa, Zenjiro Sampei, Yuichiro Sakamoto, Yukiko Okuyama-Nishida, Hiroyuki Saito, Yoshiki Kawabe, Midori Shima, Akira Yoshioka, Kunihiro Hattori
Journal: Blood (2012)
Bystander Cardiopulmonary Resuscitation: A Civic Duty
Authors: Torben K. Becker, Michael Bernhard, Bernd W. Böttiger, Jon C. Rittenberger, Mike-Frank G. Epitropoulos, Sören L. Becker
Journal: The American Journal of Bioethics (2017)

Improving the outcomes of patients suffering from cardiac arrest has been a seemingly ever-elusive goal of researchers around the world for decades. Even as survival rates have improved, high rates...
Molecular and Clinical Features of the Myeloproliferative Neoplasm Associated with JAK2 Exon 12 Mutations: a European Multicenter Study.
Authors: Francesco Passamonti, Susanne Schnittger, François Girodon, Jean-Jacques Kiladjian, Mary Frances McMullin, Marco Ruggeri, Eric Lippert, Alessandro Vannucchi, Carles Besses, Elisa Rumi, Chiara Elena, Torsten Haferlach, Cristiana Pascutto, Mario Cazzola
Journal: Blood (2009)
Imatinib Mesilate Versus Allogeneic Bone Marrow Transplantation for Patients with Chronic Myeloid Leukemia in First Chronic Phase - A Brazilian Point of View.
Authors: Henrique Bittencourt, Vaneuza Funke, Laura Fogliatto, Simone Magalhaes, Daniela Setubal, Alessandra Paz, Antonio V. Macedo, Jefferson Ruiz, Ana Paula Azambuja, Lucia M.R. Silla, Nelma Clementino, Ricardo Pasquini
Journal: Blood (2007)
Vinorelbine (N)-capecitabine (C) combination in advanced breast cancer (ABC): Long-term results of two multicentric phase II trials
Authors: M. Ghosn, G. Chahine, J. Kattan, F. Farhat, F. Nasr, W. Moukadem, J. Dagher, F. Younes, J. Gasmi
Journal: Journal of Clinical Oncology (2005)

673 Background: Vinorelbine (Navelbine)-Fluoropyrimidine has demonstrated to be an active and safe combination for ABC. Two multi centric phase II trials were conducted by the CRG/CG to assess the efficacy and safety of Navelbine-Capecitabine combination (Navcap) and Navcap followed by Docetaxel (D) as sequential block regimen (NEXT). Methods: Eligible patients (pts) had ABC, measurable disease, no prior chemotherapy for ABC, WHO PS<2, adequate bone morrow, renal and hepatic functions and written informed consent. In the Navcap study, pts received N: 25 mg/m2 on day 1 & day 8 in combination with C: 825 mg/m2 twice a day from day 1 to day 14 every 3 weeks until progression or unacceptable toxicity, while in NEXT, pts received 4 cycles of the same schedule of Navcap followed by twelve consecutive weeks of D: 25 mg/m2/w. Results: Between april 01 and Sept 03, seventy-three consecutive pts were enrolled into these 2 trials. 73.5% of pts in Navcap and 78.5% of pts in NEXT had visceral involvement, 57% of pts in both trials received anthracycline in adjuvant setting. The efficacy results are displayed in table 1. Safety results were similar for both studies, WHO grade 3–4 neutropenia was reported in 13% of pts in Navcap and 14% in NEXT, however febrile neutropenia was more frequent in NEXT (8%/2% of pts). Non-haematological toxicity was mild, Grade 3 hand-foot syndrome and mucositis were reported by one pt each in Navcap. Asthenia, diarrhea, oedema and nail disorders were frequent in NEXT (Grade 1–2 in 3% of pts). Conclusions: Navcap and block sequential of Navcap followed by D demonstrated an interesting efficacy; however the tolerance profile was slightly better for the Navcap. A phase II randomized trial is planned in order to compare the Navcap regimen with sequential Navcap followed by weekly Docetaxel (NEXT) in the first line treatment of ABC breast cancer. No significant financial relationships to disclose.
Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial
Authors: Andrew D Zelenetz, Jacqueline C Barrientos, Jennifer R Brown, Bertrand Coiffier, Julio Delgado, Miklós Egyed, Paolo Ghia, Árpád Illés, Wojciech Jurczak, Paula Marlton, Marco Montillo, Franck Morschhauser, Alexander S Pristupa, Tadeusz Robak, Jeff P Sharman, David Simpson, Lukáš Smolej, Eugen Tausch, Adeboye H Adewoye, Lyndah K Dreiling, Yeonhee Kim, Stephan Stilgenbauer, Peter Hillmen
Journal: The Lancet Oncology (2017)
Whole Exome Sequencing Reveals Spectrum of Gene Mutations in Pediatric AML
Authors: Norio Shiba, Kenichi Yoshida, Yusuke Okuno, Yuichi Shiraishi, Yasunobu Nagata, Kentarou Ohki, Motohiro Kato, Myoung-ja Park, Junko Takita, Takashi Kanazawa, Kazuko Kudo, Hirokazu Arakawa, Etsuro Ito, Masashi Sanada, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
Journal: Blood (2012)
Gender differences in outcomes for early-stage colon cancer.
Authors: Sina Alipour, Hagen F. Kennecke, Howard John Lim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

605 Background: Retrospective analyses of clinical trials suggest that gender may influence the risk of recurrence and survival in patients diagnosed with early stage colon cancer. Whether this association persists in the setting of routine clinical practice is unclear. Our aims were to 1) assess for gender differences in outcomes in early stage colon cancer and 2) evaluate if the effect of gender on outcomes is modified by adjuvant therapy (AT). Methods: Using a population-based cohort of patients diagnosed with stage II or III colon cancer and referred to any 1 of 5 regional cancer centers in British Columbia, Canada from 2001 to 2005, we compared 5-year outcomes between men and women. Multivariate Cox proportional hazard models were constructed to explore the relationships between gender and prognosis, while controlling for patient and tumor characteristics. Interaction terms between gender and AT were used to examine the predictive value of gender. Results: We included 1837 patients: 970 men and 867 women. Baseline characteristics were similar: median ages were 68 and 69 years; 39 and 38% had stage II colon cancer; and 46 and 44% received AT, respectively. Outcomes were better in women than in men (5-year cancer-specific survival rate 73 vs. 71% and 5-year overall survival rate 68 vs. 62%). In Cox regression models, women continue to experience better overall prognosis (HR for death = 0.80, 95% CI 0.69-0.92, p=0.003) when compared to men. Advanced age, stage III disease, and lack of AT also correlated with worse outcomes (all p&lt;0.01). The effect of gender on outcomes remained similar regardless of AT (HR 0.86 among women with AT and HR 0.75 among women without AT, interaction p=0.35). Conclusions: Gender is a prognostic, but not a predictive, factor for this cohort of patients with early stage colon cancer. Studies to investigate the biological mechanisms underlying this gender difference in outcomes are warranted.
High Expression of Haematopoietic Cell Specyfic Lyn Substrate-1 (HS1) Predicts Survival of B-Cell Chronic Lymphocytic Leukemia Patients
Authors: Aleksandra Butrym, Miroslaw Majewski, Justyna Dzietczenia, Tomasz Wrobel, Kazimierz Kuliczkowski, Grzegorz Mazur
Journal: Blood (2011)
Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Blocks Hairy Cell Leukemia (HCL) Survival, Proliferation, and BCR Signaling: A New Therapeutic Approach for HCL
Authors: Mariela Sivina, Robert J. Kreitman, Evgeny Arons, Joseph J. Buggy, Farhad Ravandi, Jan A. Burger
Journal: Blood (2012)
Flow Cytometric Determination of ZAP-70 Expression by SBZAP Antibody: Impact of Type of Data Analysis on Correlation with IgVH Mutation Status, Cytogenetics, and Level of ZAP-70 mRNA Expression in 351 Patients with Chronic Lymphocytic Leukemia (CLL).
Authors: Wolfgang Kern, Frank Dicker, Susanne Schnittger, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2007)
Physical activity and prostate cancer risk reduction: Does race matter?
Authors: Abhay A Singh, Jodi A Antonelli, Lee Jones, Leah Gerber, Elizabeth Ellen Calloway, Kathleen Shuler, Cathrine Hoyo, Delores Grant, Stephen J. Freedland, Lionel Lloyds Banez
Journal: Journal of Clinical Oncology (2012)

235 Background: We previously reported that physical activity may reduce prostate cancer (CaP) risk among men undergoing prostate biopsy. However, whether the potential benefit of exercise against cancer differs by race is unclear. We therefore sought to further characterize the link between physical activity and CaP risk as a function of race. Methods: Men undergoing prostate biopsy at the Durham VA Hospital were asked to complete a survey assessment of current exercise habits including frequency of differing intensities (mild, moderate and strenuous) as well as the average duration. Total current exercise was calculated by multiplying the frequency of sessions within each intensity by their average duration, weighted by the estimated metabolic equivalent (MET) and then summed across all intensities expressed as average total MET hrs/wk. Specifically, exercise intensities were as follows: mild (3 METs, e.g. easy walking), moderate (5 METs, e.g. tennis), and strenuous (9 METs, e.g. running). Quantified exercise was compared between race groups using rank sum test. Associations between exercise and CaP risk was determined using crude and adjusted logistic regression stratified by race. Results: A total of 308 men had complete data for analysis. Of these men, 53% were white and 47% were black. There was no significant difference in the amount of physical activity between race groups (p= 0.11). Increased amount of exercise was associated with decreased CaP risk for white men in both crude (OR= 0.89; 95% CI=0.81–0.98; p=0.02) and adjusted (OR=0.90; 95% CI=0.82−0.99; p=0.04) regression models that controlled for age, BMI, DRE, previous biopsy, and family history of CaP. We found no association between exercise and CaP risk among black men in both crude (p=0.79) and adjusted regression models (p=0.87). Conclusions: Increased physical activity was associated with CaP risk reduction among white men but not among black men. Further investigations to validate this potential source of CaP race disparity and to identify exercise-specific parameters that influence CaP risk reduction (ex. age-specific or cumulative exercise) are required. Investigating the race-specific mechanisms through which exercise modifies CaP risk is also warranted.
Prognostic factors for survival in early-phase trials in hematology.
Authors: R. Jamal, G. Hristova, C. Holcroft, S. E. Assouline
Journal: Journal of Clinical Oncology (2011)

e13094 Background: Although strict criteria are used to limit toxicity for cancer patients (pts) enrolled in phase I/II clinical trials, one of these, the ability to survive beyond 12 weeks, is subjective and error-prone. A prognostic score using low albumin (Alb), high lactate dehydrogenase (LDH) and >2 sites of metastasis was designed and validated as an independent predictor of OS in pts with solid tumors included in phase I trials (Arkenau, BJC 2008; JCO 2009). Similarly, we examined the ability of objective clinical measures to predict OS in pts with hematologic malignancies enrolled in early-phase trials. Methods: A retrospective analysis was conducted on 63 consecutive pts, 30 in phase I and 33 in phase II trials between 01/2006 and 10/2009. Pts received either combination drugs (n=15), monoclonal antibody (n=12) or single agent drugs (n=36). Median age was 62 yrs (37-86). ECOG performance status (PS) was 0, 1 and 2 in 48, 47 and 5% of pts, respectively. There were 52% of pts with lymphoma (LY) and chronic lymphocytic leukemia (CLL), and 48% with acute leukemia (AL). Median follow-up time, time on study, and OS were 16.4, 7.9, and 31 weeks, respectively. Clinical variables were collected and univariate (UA) and multivariable analyses (MVA) using proportional hazards regression were performed. Results: In the UA, diagnosis (Dg), type of treatment, phase of study, ECOG PS, Alb, LDH, hemoglobin, and granulocyte count were significant (p≤0.05). Gender, age>65, white blood cell count, platelet count, lymphopenia, alkaline phosphatase and uric acid were not. MVA assessed the same variables. LDH, Dg and lymphopenia were found to be significant (p≤0.05, Table 1). Alb was also significant when the significance level was set to 0.1. Conclusions: In this sample, LDH and Alb independently predicted OS, mirroring Arkenau's findings. Dg and lymphopenia were predictors specific to these patients with hematologic malignancies. A larger cohort will be needed to reinforce these findings. Variable MVA HR (95%CI, p value) p≤0.05 p≤0.1 Alb <35g/L - 2.38 (0.92-6.18, 0.074) LDH >220 U/L 2.94 (1.33-6.48, 0.007) 2.70 (1.22-6.00, 0.015) Lymphopenia <1.2x109/L 2.03 (1.00-4.11, 0.049) 2.07 (1.02-4.18, 0.044) Dg (AL vs. CLL/LY) 3.55 (1.74-7.25, 0.001) 3.36 (1.64-6.89, 0.001)
Host Prothrombin and Fibrinogen Support S. Aureus Virulence In the Context of Acute Bacteremia
Authors: Matthew J. Flick, Xinli Du, Leslie Fausnacht, Harini Raghu, Kathryn E Talmage, Keith W Kombrinck, Elizabeth A. Blevins, Eric S. Mullins, Joseph S. Palumbo, Jay L. Degen
Journal: Blood (2010)
Next-Generation Sequencing for the Identification of Transplantation-Associated Pathogens
Authors: Ami S. Bhatt, Samuel S Freeman, Alex F Herrera, Chandra Sekhar Pedamallu, Dirk Gevers, Fujiko Duke, Joonil Jung, Bruce J Walker, Sarah Young, Ashlee Earl, Aleksandar Kostic, Akinyemi I. Ojesina, Gabriela Soriano, Joseph H. Antin, Robert J. Soiffer, Lindsey R Baden, Jason L Hornick, Francisco M Marty, Matthew Meyerson
Journal: Blood (2012)
Central role of the TIR‐domain‐containing adaptor‐inducing interferon‐β (TRIF) adaptor protein in murine sterile liver injury
Authors: Katherine J. Brempelis, Sebastian Y. Yuen, Nicole Schwarz, Isaac Mohar, Ian N. Crispe
Journal: Hepatology (2017)

Multiple pathways drive the sterile injury response in the liver; however, it is unclear how the type of cells injured or the mechanism of injury activates these pathways. Here, we use a model of selective hepatocyte death to investigate sterile liver injury. In this model, the TIR‐domain‐containing adaptor‐inducing interferon‐β (TRIF) was a central mediator of the resulting intrahepatic inflammatory response that was independent of both upstream Toll‐like receptor (TLR) 4 signaling and downstream type I interferon (IFN) signaling. TRIF was required for induction of interleukin (IL)‐10, IL‐6, and IL‐1β cytokines. Conversely, although induction of C‐C motif chemokine ligand (CCL) 2 and C‐X‐C motif chemokine ligand (CXCL) 1 chemokines and up‐regulation of chemokine ( Ccl2 , Ccl7, Cxcl1 , Cxcl2 , and Cxcl10 ) and cell‐adhesion (intracellular adhesion molecule 1 and vascular cell adhesion molecule 1) genes involved in myeloid cell recruitment was reduced in a majority of TRIF –/– mice, a subset of TRIF –/– mice showed breakthrough inflammation and the ability to induce these genes and proteins, indicating that redundant pathways exist to respond to hepatocyte death. Furthermore, we found that hepatocytes themselves were the main responders to hepatocyte death, increasing transcription of genes involved in myeloid cell recruitment more than either liver sinusoidal endothelial cells or Kupffer cells. Conclusion : Our studies define a TRIF‐dependent, TLR4‐ and type I IFN‐independent pathway of sterile liver injury in which hepatocytes are both the targets of damage and the principal responding cell type. (H epatology 2017;65:1336‐1351).
NHS chief wants big overhaul of medical training
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The head of the NHS in England has told The BMJ that he will push for a major overhaul of medical training to focus more on the needs of the modern NHS and rejuvenate morale among the junior workforce.

NHS England’s chief executive, Simon Stevens, said that he wanted to use the government’s recent announcement of 1500 extra medical school places by 2018 as a springboard for change to how doctors are trained.1 This refocus should include a stronger emphasis on primary care and psychiatry and an increased recognition of the importance of multimorbidity and frailty, he said.

Alongside this, Stevens said that the NHS would work urgently to provide a more …
Relationship between high microRNA-200C expression and the risk of death from disease in muscle-invasive urothelial carcinoma of the bladder.
Authors: Neema Navai, Michael Brandon Williams, Sijin Wen, Arlene O. Siefker-Radtke, David James McConkey, Colin P.N. Dinney, Liana Adam
Journal: Journal of Clinical Oncology (2012)

279 Background: Bladder cancer represents both a common and highly morbid disease with limited tools for prognostication. Recently molecular studies have led to promising targets to inform disease behavior, including microRNAs (miRNA). miRNAs are non-coding RNAs, with widespread effects on cellular function. Our group has demonstrated that the miR200 family members play an integral role in epithelial to mesenchymal transition (EMT) via an inverse relationship with ZEB1 and a direct relationship with E-cadherin. EMT is seen as a necessary step for invasion and metastasis, however, studies have indicated a significant role for mesenchymal to epithelial transition (MET) to drive proliferation after cells have reached metastatic locations. Members of the miR200 family have been shown to induce MET and we hypothesize that miR200c, as a surrogate marker for MET, and will predict disease survival in muscle invasive urothelial carcinoma (MIUC). Methods: A clinically diverse sample set was obtained consisting of 101 unique specimens upon which real-time PCR miRNA analysis was performed. Regression tree analysis and best-fit modeling was used to establish the most discriminating relative miR200c expression level to predict disease specific survival. Fisher exact test was carried out to compare clinical variables, Kaplan-Meier estimate of survival distribution based on miR200c expression and univariate log-rank test was used to compare survival distributions between groups. Multivariate analysis was done via the proportional hazards model. A p-value of &lt;0.05 was considered significant for all statistical analyses. Results: Patients with high miRNA200c had significantly more deaths (69 vs. 47%). In multivariable analysis of patients with MIUC miR200c expression was associated with the highest risk of death (RR 2.7). Lymph node involvement (RR 2.0) and age &gt; 65yrs (RR 2.4) were also strong predictors of survival. High miR200c had lower median survival for all patients (59 vs 16 months; p = 0.039) and those with MIUC (41 vs 8 months; p = 0.0004). Conclusions: High miR200c expression is associated with a higher risk of death from bladder cancer in patients with muscle invasive disease.
Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions
Authors: E. Hagforsen, M. Lampinen, A. Paivandy, S. Weström, H. Velin, S. Öberg, G. Pejler, O. Rollman
Journal: British Journal of Dermatology (2017)

Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells. The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions. Punch biopsies were obtained from lesional and uninvolved skin in 25 patients with chronic plaque psoriasis. After incubation with siramesine, the number of tryptase‐positive mast cells and their expression of interleukin (IL)‐6 and IL‐17 was analysed. Skin biopsies were digested to allow flow cytometric analysis of the drug's effect on cutaneous fibroblasts and keratinocytes. Siramesine caused a profound reduction in the total number of mast cells in both lesional and uninvolved psoriatic skin biopsies without affecting the gross morphology of the tissue. The drug reduced the density of IL‐6‐ and IL‐17‐positive mast cells, and showed antiproliferative effects on epidermal keratinocytes but had no apparent cytotoxic effect on keratinocytes or dermal fibroblasts. Considering the pathophysiology of psoriasis, the effects of siramesine on cutaneous mast cells may prove favourable from the therapeutic aspect. The results encourage further studies to assess the usefulness of siramesine and other lysosomotropic agents in the treatment of cutaneous mastocytoses and inflammatory skin diseases aggravated by dermal mast cells.
Treatment of High Risk AML and MDS with Ara-C-Containing Standard Chemotherapy Followed by Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (RIC-SCT) during Aplasia: A Survey of the German Cooperative Transplant Study Group (GCTSG).
Authors: Jolanta B. Dengler, Matthias Stelljes, Cathrin Theuser, Ute Hegenbart, Christoph Schmid, Joachim Kienast, Anthony D. Ho, Gerhard Ehninger, Peter Dreger, Martin Bornhaeuser
Journal: Blood (2006)
Molecular cloning and functional identification of a cDNA encoding 4-hydroxy-3-methylbut-2-enyl diphosphate reductase from Tripterygium wilfordii
Authors: Qiqing Cheng, Yuru Tong, Zihao Wang, Ping Su, Wei Gao, Luqi Huang
Journal: Acta Pharmaceutica Sinica B (2017)

The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the last step key enzyme of the methylerythritol phosphate (MEP) pathway, synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which is important for regulation of isoprenoid biosynthesis. Here the full-length cDNA of HDR, designated TwHDR (GenBank Accession No. KJ933412.1), was isolated from Tripterygium wilfordii for the first time. TwHDR has an open reading frame (ORF) of 1386 bp encoding 461 amino acids. TwHDR exhibits high homology with HDRs of other plants, with an N-terminal conserved domain and three conserved cysteine residues. TwHDR cDNA was cloned into an expression vector and transformed into an Escherichia coli hdr mutant. Since loss-of-function E.coli hdr mutant is lethal, the result showed that transformation of TwHDR cDNA rescued the E.coli hdr mutant. This complementation assay suggests that the TwHDR cDNA encodes a functional HDR enzyme. The expression of TwHDR was induced by methyl-jasmonate (MJ) in T. wilfordii suspension cells. The expression of TwHDR reached the highest level after 1 h of MJ treatment. These results indicate that we have identified a functional TwHDR enzyme, which may play a pivotal role in the biosynthesis of diterpenoid triptolide in T. wilfordii.
Comparison of Donor KIR Genotype, Recipient CMV Reactivation and Pretransplant MRD in Predicting Relapse after Ex Vivo T-Deplete Allohsct
Authors: Robert Q. Le, Prathima Anandi, Xin Tian, Sawa Ito, Natasha A Jain, Meghali Goswami, Catherine E. Lai, Christopher S. Hourigan, Sharon Adams, Nancy F. Hensel, Austin John Barrett, Minoo Battiwalla
Journal: Blood (2015)
FTY720 Inhibits Graft-Versus-Host Disease (GVHD) and Allogeneic Bone Marrow (BM) Graft Rejection Independent of Effects on T Cell Egress from Lymphoid Tissue.
Authors: Patricia A. Taylor, Michael J. Ehrhardt, Angela Panoskaltsis-Mortari, Jonathan S. Serody, Volker Brinkmann, Bruce R. Blazar
Journal: Blood (2006)