tbuckley/cabot-search huggingface dataset:
Model-based predictions of expected anti-tumor response and survival in phase III studies based on phase II data of an investigational agent
Authors: L. Claret, P. Girard, J. O’shaughnessy, P. Hoff, E. Van Cutsem, J. Blum, K. Zuideveld, K. Jorga, J. Fagerberg, R. Bruno
Journal: Journal of Clinical Oncology (2006)

6025 Background: Decision making during early oncology drug development remains very empirical. A drug-disease simulation model to predict expected clinical response and survival in phase III studies from observed longitudinal tumor size in phase II trials offers a science-based alternative. Methods: We developed the following: 1) longitudinal exposure-response models of drug effect (and resistance) on tumor growth dynamics based on phase II data on capecitabine (X) in metastatic breast (MBC) and colorectal cancer (MCRC) and on historical phase III data on docetaxel (T) in MBC and 5-FU in MCRC; and 2) a survival model relating change in tumor size and patient characteristics to survival time in MBC and MCRC based on phase III data. The models were validated and used to predict expected anti-tumor response and survival in phase III studies of XT vs. T alone in MBC and X vs. 5-FU in MCRC. Multiple replicates (n = 1000) of simulated phase III studies were compared to actual results. Results: Change of tumor size and survival time distributions in X arms were well predicted. In MBC, expected median (90% prediction interval) survival for patients treated with XT was 412 (range 330 to 526) days (vs. 431 days observed) with an improvement over T of 57 days (range -17 to 148) (vs. 78 days observed). For MCRC patients, X treatment resulted in a potential survival improvement of 39 (range -21 to 110) days (vs. 35 days observed) compared to patients treated with 5-FU. Conclusions: The dose-tumor size-survival model succeeded in predicting survival in phase III trials based on X phase II data in MBC (in combination with T) and as a single agent in MCRC. This model is a useful tool to compare expected clinical response of new compounds to various competitors and to support end-of-phase II decisions and design of phase III studies. [Table: see text]
Endogenous Bioelectric Signaling Networks: Exploiting Voltage Gradients for Control of Growth and Form
Authors: Michael Levin, Giovanni Pezzulo, Joshua M. Finkelstein
Journal: Annual Review of Biomedical Engineering (2017)

Living systems exhibit remarkable abilities to self-assemble, regenerate, and remodel complex shapes. How cellular networks construct and repair specific anatomical outcomes is an open question at the heart of the next-generation science of bioengineering. Developmental bioelectricity is an exciting emerging discipline that exploits endogenous bioelectric signaling among many cell types to regulate pattern formation. We provide a brief overview of this field, review recent data in which bioelectricity is used to control patterning in a range of model systems, and describe the molecular tools being used to probe the role of bioelectrics in the dynamic control of complex anatomy. We suggest that quantitative strategies recently developed to infer semantic content and information processing from ionic activity in the brain might provide important clues to cracking the bioelectric code. Gaining control of the mechanisms by which large-scale shape is regulated in vivo will drive transformative advances in bioengineering, regenerative medicine, and synthetic morphology, and could be used to therapeutically address birth defects, traumatic injury, and cancer.
Topiramate (Top) in the treatment of neuropathic pain (Np) in cancer patients (pts)
Authors: E. A. Bendaly, C. A. Jordan, S. A. Staehler, D. A. Rushing
Journal: Journal of Clinical Oncology (2006)

18589 Background: Top relieves Np by four direct and one indirect method, compared to most other anti-epileptics that relieve Np by one. Methods: Seventeen cancer pts treated with Top for Np were found on retrospective chart review of Palliative Care Clinics at Indiana University Hospital and Roudebush VA. Pain was assessed by physician serial follow-up. Results: Mean age was 53.8 years; 53.8 % were males. Four pts were not included in statistical analysis for efficacy, one for incomplete follow’up, and 3 had their pain decrease in frequency by 25 to 75 % but not in severity. Of the remaining 13 pts, 69% had previous gabapentin use, 85% had previous tricyclic use, and all were on opioids. Most common Np sites were extremity (53.8%), trunk (30.8%), and face (15.4%). Most common Np characteristics included burning (61.5%), pins and needles (30.8%), and sharp (15.4%). Np was related directly to active tumor in 38.5%, previous surgery in 43.8%, and chemotherapy in 11.7%. Mean duration of Top therapy was 6 months; mean total daily dose was 173 mg. 61.5% were current users. Pts had Np for 27.3 months on average prior to starting Top. All 13 pts were using Top as second-line therapy; 69.2% had tried another anticonvulsant, and 92.3% used antidepressants. 53.8% experienced Top-related adverse effects (AEs). These included change of taste (15.4%), dose-dependent, transient, memory loss (23.1%), depression (15.4%), nausea (7.7%), chest pain (7.7%), and fatigue (7.7%). 29.4% discontinued Top due to AEs. Using two-tailed paired testing, mean decrease in worst pain was from 8.7 to 5.6 (p &lt; .001), in average pain from 6.4 to 2.4 (p = .0004), and in least pain from 4.4 to 1.5 (p &lt; .03). Conclusions: Top was associated with improvements in Np in a high proportion of pts with refractory Np. Pts tolerated Top therapy well as indicated by the average duration of therapy. Further studies of Top in cancer-related Np are indicated, particularly as first-line therapy. No significant financial relationships to disclose.
The Novel Kinesin Spindle Protein Inhibitor SB-743921 Exhibits Marked Activity In In Vivo and In Vitro In Models of Aggressive Diffuse Large B-Cell Lymphoma
Authors: Danielle C Bongero, Luca Paoluzzi, Enrica Marchi, Neisa Roberto, Rafael Escandon, Ken Wood, Owen A. O'Connor
Journal: Blood (2010)
Anti-Thymocyte Globulin Induces Higher Response Rates and Less Graft-Versus-Host Disease in Multiple Myeloma Patients Undergoing Allogeneic Stem Cell Transplantation.
Authors: Francis Ayuk, José A. Perez-Simon, Avichai Shimoni, Anna Sureda, Tatjana Zabelina, Rainer Schwerdtfeger, Rodrigo Martino, Herbert G. Sayer, Adrián Alegre, Juan-José Lahuerta, Djordje Atanackovic, Christine Wolschke, Arnon Nagler, Axel R. Zander, Jesús San Miguel, Nicolaus Kroeger
Journal: Blood (2007)
Molecular Monitoring of ERG and BAALC as Minimal Residual Disease Markers in Patients with Acute Leukemia.
Authors: Yuho Najima, Kazuteru Ohashi, Kazuhiko Kakihana, Taku Kikuchi, Yasunobu Nagata, Chihiro Sakurai, Toshimitsu Ueki, Takeshi Kobayashi, Takuya Yamashita, Machiko Kawamura, Hideki Akiyama, Hidefumi Kaku, Hisashi Sakamaki
Journal: Blood (2007)
GW26-e2253 An Imaging-based Renal Denervation Strategy in Hypertensive Canines Using Integrated Ultrasound Catheter
Authors: Jun Qian, Yuanyi Zheng, Gang Yang, Shunkang Rong, Yonghong Jiang, Qi Zhou, Que Zhu, Dengqing Zhang, Rui Xue, Yuanqing Yao, Changming Deng, Dichuan Liu, Pan Li, Zhigang Wang, Tong-Chuan He, Han Lei, Jing Huang
Journal: Journal of the American College of Cardiology (2015)
IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis
Authors: Ankit Malik, Deepika Sharma, Qifan Zhu, Rajendra Karki, Clifford S. Guy, Peter Vogel, Thirumala-Devi Kanneganti
Journal: Journal of Clinical Investigation (2016)

Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1α, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1α ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1α-dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1α, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC.
GW26-e2106 The Impact of the Drug Composition Containing Medicine Serum Contains Cassia Twig Liquorice Decoction Components on ICa- L of Guinea Pig Single Ventricular Myocyte
Authors: Yongxia Wang, Zuoying Xing, Chulin Zhu, Yingjie Cao, Shuangxing Yuan, Hongjun Liu, Youping Wang, Yuan Gao, Bin Li, Mingjun Zhu
Journal: Journal of the American College of Cardiology (2015)
Increased Activity in the T Cell Effector Phase and Enhanced T Cell Repertoire Target-Tissue Stability Distinguish Alloreactivity Across Major Versus Minor Histocompatibility Barriers
Authors: Pingping Zheng, Adrianne E Vasey, Jeanette Baker, Bettina Iliopoulou, Dennis B Leveson-Gower, Antonio Pierini, Dominik Schneidawind, Xiaoqing You, Katie Hsu, Robert Negrin, Everett Meyer
Journal: Blood (2015)
David Oliver: Let’s argue about statistics
Authors: David Oliver
Journal: BMJ (2016)

In his recent speech to the Conservative Party conference the health secretary, Jeremy Hunt, used statistics enthusiastically.1 I counted at least 27 times that he mentioned numerical data. And he made several more assertions about numbers, such as, “Safer care doesn’t cost more; it costs less.” Not bad for a speech of 23 minutes.2

He used statistics to take credit on behalf of his government for purported greater NHS activity. Then he used data to highlight poor or inconsistent NHS performance to justify reforms. And he cited data in support of his commitment to an uncosted “seven day …
Hematopoietic Cell Mobilization for Gene Therapy of Adult Patients with Severe Beta-Thalassemia: The Challenge of Splenectomy and the Role of Plerixafor
Authors: Evangelia Yannaki, Thalia Papayannopoulou, Erica Jonlin, Fani Zervou, Garyfalia Karponi, Angeliki Xagorari, Pamela S. Becker, Nikoleta Psatha, Ioannis Batsis, Panayotis Kaloyannidis, Varvara Tahynopoulou, Varnavas Constantinou, Asimenia Bouinta, Konstantia Kotta, Aglaia Athanassiadou, Achilles Anagnostopoulos, Athanasios Fassas, George Stamatoyannopoulos
Journal: Blood (2011)
Genetic Polymorphisms in Chemokine Receptor 5, Interleukin 10 and Monocyte Chemoattractant Protein 1 Contribute to Cytomegalovirus Reactivation and Disease after Allogeneic Stem Cell Transplantation.
Authors: Juergen Loeffler, Michael Steffens, Eva-Maria Arlt, Mohammad-Reza Toliat, Thomas Wienker, Holger Hebart, Michael Boeckh, Per Ljungman, Rudolf Trenschel, Hermann Einsele
Journal: Blood (2005)
Diagnostic value of imaging in infective endocarditis: a systematic review
Authors: Anna Gomes, Andor W J M Glaudemans, Daan J Touw, Joost P van Melle, Tineke P Willems, Alexander H Maass, Ehsan Natour, Niek H J Prakken, Ronald J H Borra, Peter Paul van Geel, Riemer H J A Slart, Sander van Assen, Bhanu Sinha
Journal: The Lancet Infectious Diseases (2016)
Aortic stenosis: diagnosis and management
Authors: M Zakkar, A J Bryan, G D Angelini
Journal: BMJ (2016)

#### What you need to know

The overall prevalence of clinically significant aortic stenosis in patients >70 years old in Europe is approximately 1-3%, making it the most common valvular heart diseases in developed countries.1 2 3 4 Aortic stenosis is a narrowing of the aortic valve that results in restricted blood flow to the body and eventually compromised heart function. Aortic sclerosis is the thickening and calcification of aortic leaflets without motion restriction (fig 1⇓). Aortic sclerosis affects one in four of patients >65 years old in developed countries.



Fig 1  Anatomy and function of the aortic valve. The valve controls blood flow from the heart by allowing unobstructed forward flow during systole and preventing blood return to the heart during diastole. It is made of three leaflets in most patients. In aortic stenosis, calcific degeneration of the aortic leaflets reduces opening and prevents full closure



This review describes the causes, pathophysiology, presentation, and treatment of aortic stenosis.1 2 3 4

Calcific degeneration of aortic leaflets is the most common cause of aortic stenosis in patients >70 years old in developed countries. The leading cause of aortic stenosis in younger patients is bicuspid aortic valve. This is a congenital abnormality in which the valve is made of two leaflets rather than the normal three leaflet configuration and occurs in 1-2% of the general population in developed countries. Other causes are listed in box 1.2 3 5

#### Box 1: Causes of aortic stenosis

Degenerative changes …
β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis
Authors: Bryan Saunders, Kirsty Elliott-Sale, Guilherme G Artioli, Paul A Swinton, Eimear Dolan, Hamilton Roschel, Craig Sale, Bruno Gualano
Journal: British Journal of Sports Medicine (2016)

To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance.This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data.3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine').Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses.40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)).β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-alanine supplementation based on their chosen exercise modality.
Impact of pre-operative chemotherapy on the quality of life (QL) of patients with resectable non-small cell lung cancer (NSCLC): Experience from the MRC LU22/NVALT/EORTC 08012 multicentre randomised trial
Authors: P. Hopwood, M. Nankivell, C. Pugh, D. Gilligan, M. Nicolson, R. J. Stephens
Journal: Journal of Clinical Oncology (2007)

9020 Aim: To evaluate QL during the first 2 years follow-up in patients randomised to receive 3 cycles of platinum-based chemotherapy (CT-S) prior to surgical resection of NSCLC compared to those receiving surgery alone (S). Methods: A total of 519 patients were entered into the LU22 trial from 70 centres in the UK, The Netherlands, Germany and Belgium. All patients were asked to complete the SF-36 QL questionnaire prior to randomisation and at 6 and 12 months then annually to 5 years. The scores from the SF-36 questionnaire were combined into 8 domains and also summarised as physical component summary (PCS) and mental component summary (MCS). The 6,12 and 24 month PCS and MCS scores were analysed using multivariable regression to identify prognostic factors and investigate the difference between the regimens. Results: 82% patients completed QL at baseline, and compliance at 6, 12 and 24 months was 59%, 60% and 67% respectively. Median age was 63 (range 25 to 79 years) and 72% were male. At 6 months patients in the S group reported somewhat better functioning in all domains except general health and mental health, but no differences were seen at 12 or 24 months. The regression analyses indicated that better physical health outcomes (PCS) were predicted by baseline PCS and MCS at all follow-up points (all p&lt;0.05), whereas longer time since surgery predicted better PCS at 6 months (p&lt;0.05), and younger age predicted better PCS at 24 months (p=0.07). For mental health, better MCS was predicted at all time points by baseline MCS (p&lt;0.05). In addition, female gender (p=0.07), and PCS (p&lt;0.05), were predictors at 6 months, and younger age predicted better MCS at 24 months (p&lt;0.01). Treatment regimen had no effect on QL at any time point. At 1 and 2 years more than 50% patients considered their health comparable to others, and 45% were generally optimistic about their future health. Conclusions: Over 2 years follow-up, QL was not adversely affected by pre-operative chemotherapy and there were no significant differences between the regimens. Many patients saw themselves as fit as their contemporaries. [Table: see text]
Elevation of Plasma Leukotriene B4 on G-CSF-Induced Hematopoietic Stem Cells Mobilization In Normal Individuals
Authors: Yeung-Chul Mun, Jee Young Ahn, Solip Lee, Eun-Sun Yoo, Jung Yeon Cho, Kyoung Eun Lee, Eun Mi Nam, Soon Nam Lee, Chu-Myong Seong
Journal: Blood (2010)
NICE algorithms based on high sensitivity troponin assays ruled out AMI but &gt; 8.5% had MACE at 30 d
Authors: Benton R. Hunter
Journal: Annals of Internal Medicine (2016)

Source Citation Parsonage WA, Mueller C, Greenslade JH, et al. Validation of NICE diagnostic guidance for rule out of myocardial infarction using high-sensitivity troponin tests. Heart. 2016;102:1279-86. 27288278
High-dose sequential chemotherapy and rituximab (R-HDS) supported by autologous stem cell transplantation (ASCT) in patients (pts) with systemic B-cell lymphoma with CNS involvement (SCNSL) at diagnosis or relapse: Interim analysis of feasibility and activity of a phase II trial.
Authors: A. Assanelli, K. Patti, S. Cortelazzo, L. Rigacci, L. Devizzi, M. Foppoli, A. Mule', F. Ciceri, C. Tarella, A. J. Ferreri
Journal: Journal of Clinical Oncology (2010)

8081 Background: High-dose (HD) chemotherapy supported by ASCT exhibited promising results in a few, small retrospective series of SCNSL. Herein we report the interim analysis of a phase II trial (ClinicalTrials.gov #NCT00801216) addressing a new R-HDS combination with ASCT in these poor-prognosis pts. Methods: Pts (≤65 ys old; ECOG PS 0-3) with SCNSL at diagnosis or relapse were treated with 2 c. of HD-methotrexate + HD-cytarabine (induction); 3 sequential c. of HD-cyclophosphamide, HD-cytarabine, HD-etoposide (R-HDS); BCNU-thiotepa-based conditioning and ASCT. Pts received 6 doses of i.v. rituximab and 4 doses of intrathecal liposomal cytarabine. Pts with CNS residual disease were referred to RT. The 2-year EFS is the primary endpoint (P0 40%; P1 60%; 38 pts required). This approach will be considered active if ≥21 pts will be progression free at 2 yrs. Results: the first 13 registered pts (median age 52 ys, 31-65; M/F ratio 1.6) were analyzed. Six pts were treated at diagnosis; 8 had systemic disease; no pt had positive CSF. Histotypes were diffuse large B-cell (10), mantle cell (2) and follicular (1) lymphomas. Bulky disease (1), ECOG-PS 2-3 (4) and B-symptoms (1) were uncommon; elevated LDH levels were observed in 10 pts. Treatment was completed in 8 pts, is ongoing in 3 (R-HDS), and was interrupted in 2: before conditioning in a poor mobilizer and after the first course due to PD. There were no toxic deaths. G4 neutropenia and thrombocytopenia were reported in all pts, febrile neutropenia in 7, other septic complications in 5. G3-4 non-hematological toxicity was not reported. PBSC collection was successful in 8 of the 9 referred pts (median 9.35 × 109/kg). Nine (69%) pts achieved a CR, 3 a PR (ORR 92%), 1 pt had PD. No pt received RT. At a median f-up of 15 m, 4 pts experienced relapse/PD (CNS 3, extra-CNS 1), with a 2-yr EFS of 46%; 9 pts are alive with a 2-yr OS of 54%. Conclusions: R-HDS supported by ASCT is feasible in pts ≤65 ys old with SCNSL. Preliminary results with this intensive approach are encouraging in this condition, with otherwise dismal prognosis. No significant financial relationships to disclose.
Antifungal Therapy with Itraconazole Impairs Rituximab′s Anti-Lymphoma Effect by Inhibiting CD20 Recruitment to Lipid Rafts.
Authors: Christian Meyer zum Bueschenfelde, Yvonne Feuerstacke, Philipp Krainz, Ken Herrmann, Andreas Buck, Christian Peschel, Ingo Ringshausen
Journal: Blood (2009)
P0200 : Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: A meta-analysis of controlled trials
Authors: P. Deltenre, E. Trépo, M. Rudler, A. Monescillo, M. Fraga, A. Denys, C. Doerig, N. Fournier, C. Moreno, D. Moradpour, C. Bureau, D. Thabut
Journal: Journal of Hepatology (2015)
A case treated with nivolumab after small cell lung cancer transformation of mutant EGFR non-small cell lung cancer
Authors: S. Nishikawa, Y. Tambo, H. Ninomiya, T. Oguri, Y. Kawashima, N. Takano, S. Kitazono, F. Ohyanagi, A. Horiike, N. Yanagitani, Y. Ishikawa, M. Nishio
Journal: Annals of Oncology (2016)
Xenotransplantation of Primary CD34+CD38- Hematopoietic Stem Cells Results in an In Vivo Model of Idiopathic Myelofibrosis.
Authors: Noriyuki Saito, Fumihiko Ishikawa, Kazuya Shimoda, Shuro Yoshida, Yoriko Saito, Noriaki Kawano, Leonard D. Shulz, Koichi Akashi, Mine Harada
Journal: Blood (2006)
Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium 90 Ibritumomab Tiuxetan (Zevalin) in Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL).
Authors: Parameswaran Venugopal, Stephanie A. Gregory, Teresa Obrien, Ray Drasga, Robert Bayer
Journal: Blood (2007)
A Phase I Study of a Combination of 5-Azacyitidine Followed by Lenalidomide In High-Risk MDS or AML Patients with Chromosome 5 Abnormalities – Interim Results of the “AZALE” Trial
Authors: Uwe Platzbecker, Detlef Haase, Friederike Braulke, Gesine Bug, Katharina Götze, Andrea Kuendgen, Christoph Röllig, Martin Wermke, Ralph Naumann, Martin Bornhäuser, Aristoteles Giagounidis, Ulrich Germing, Wolf-Karsten Hofmann, Gerhard Ehninger
Journal: Blood (2010)
Gentuzumab-Ozogamicin,Citosine Arabinoside, G-CSF Combination in the Treatment of Elderly Poor Prognosis Acute Myeloid Leukemia. A Multicentric Study.
Authors: Luana Fianchi, Franco Leoni, Sergio Storti, Sergio Rutella, Giacomo Gianfaldoni, Maria Teresa Voso, Stefano Bosi, Livio Pagano, Giuseppe Leone
Journal: Blood (2005)
A Novel Antisense Long Noncoding RNA Modulates NR4A1 Protein Level in Myeloid Malignancies
Authors: Flávia Adolfo Corrocher, Ada Congrains, Fernanda Soares Niemann, Bruna Palodetto, Fernanda Marconi Roversi, Mariana Ozello Baratti, Paula de Melo Campos, Sara Teresinha Olalla Saad
Journal: Blood (2015)