tbuckley/cabot-search huggingface dataset:
Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells
Authors: Tze-Sian Chan, Chung-Chi Hsu, Vincent C. Pai, Wen-Ying Liao, Shenq-Shyang Huang, Kok-Tong Tan, Chia-Jui Yen, Shu-Ching Hsu, Wei-Yu Chen, Yan-Shen Shan, Chi-Rong Li, Michael T. Lee, Kuan-Ying Jiang, Jui-Mei Chu, Gi-Shih Lien, Valerie M. Weaver, Kelvin K. Tsai
Journal: The Journal of Experimental Medicine (2016)

Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy–treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif–positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy.
Health professionals’ stereotyping is impeding suicide prevention efforts
Authors: Caroline White
Journal: BMJ (2016)

The stereotyping of people amid a mental health crisis is hampering efforts in mainstream care services in England to bring down the toll of deaths by suicide, a parliamentary inquiry has heard.

The House of Commons Health Committee is looking at what further action needs to be taken ahead of the planned refresh of the previous coalition government’s suicide prevention strategy for England, published in 2012.1

A progress report two years on showed that 4727 people died by suicide in 2013 and that between 2011 and 2013 (the latest period for which data are available) the suicide rate was 8.8 per 100 000 of the population, the same as in 2004-06.2

Expert witnesses …
Kruppel-Like Factor 10 (KLF10)-Deficient Mice Have Marked Defects In EPC Differentiation, Function, and Angiogenesis
Authors: Akm Khyrul Wara, Kevin Croce, ShiYin Foo, Xinghui Sun, Basak Icli, Yevgenia Tesmenitsky, Zhuoxiao Cao, Fehim Esen, Malayannan Subramaniam, Jeffery Kutok, Scott J. Rodig, Thomas Spelsberg, Anthony Rosenzweig, Mark Feinberg
Journal: Blood (2010)
Long-Term Follow-up of Survival, Complications, Arsenic Retention and Quality of Life in Patients with Newly Diagnosed Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid/Arsenic Trioxide Combination Therapy
Authors: Hongming Zhu, Jiong Hu, Li Chen, Wei Zhou, Xiaoyang Li, Wang Lining, Xia Zhao, Yunxiang Zhang, Huijin Zhao, Yu Chen, Huiping Sun, Qiusheng Chen, Yu Chen, Weili Zhao, Jianqing Mi, Zhixiang Shen, Saijuan Chen, Zhenyi Wang, Junmin Li
Journal: Blood (2014)
Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack
Authors: Kwang-Zin Lee, Matthieu Lestradet, Catherine Socha, Stefanie Schirmeier, Antonin Schmitz, Caroline Spenlé, Olivier Lefebvre, Céline Keime, Wennida M. Yamba, Richard Bou Aoun, Samuel Liegeois, Yannick Schwab, Patricia Simon-Assmann, Frédéric Dalle, Dominique Ferrandon
Journal: Cell Host & Microbe (2016)
Predictors of Avascular Necrosis (AVN) of Bone after Long-Term Follow-Up of Allogeneic and Autologous Hematopoietic Cell Transplantation (HCT) for Malignant and Non-Malignant Disorders.
Authors: Liton Francisco, Stephanie Campbell, Andrea Carter, Roberto Rodriguez, Joseph Rosenthal, Carol Schroeder, Marianna Shakhnovits, Stephen J. Forman, Smita Bhatia
Journal: Blood (2005)
Dual modulation of MCL-1 and mTOR determines the response to sunitinib
Authors: Mohamed Elgendy, Amal Kamal Abdel-Aziz, Salvatore Lorenzo Renne, Viviana Bornaghi, Giuseppe Procopio, Maurizio Colecchia, Ravindran Kanesvaran, Chee Keong Toh, Daniela Bossi, Isabella Pallavicini, Jose Luis Perez-Gracia, Maria Dolores Lozano, Valeria Giandomenico, Ciro Mercurio, Luisa Lanfrancone, Nicola Fazio, Franco Nole, Bin Tean Teh, Giuseppe Renne, Saverio Minucci
Journal: Journal of Clinical Investigation (2016)

Most patients who initially respond to treatment with the multi-tyrosine kinase inhibitor sunitinib eventually relapse. Therefore, developing a deeper understanding of the contribution of sunitinib's numerous targets to the clinical response or to resistance is crucial. Here, we have shown that cancer cells respond to clinically relevant doses of sunitinib by enhancing the stability of the antiapoptotic protein MCL-1 and inducing mTORC1 signaling, thus evoking little cytotoxicity. Inhibition of MCL-1 or mTORC1 signaling sensitized cells to clinically relevant doses of sunitinib in vitro and was synergistic with sunitinib in impairing tumor growth in vivo, indicating that these responses are triggered as prosurvival mechanisms that enable cells to tolerate the cytotoxic effects of sunitinib. Furthermore, higher doses of sunitinib were cytotoxic, triggered a decline in MCL-1 levels, and inhibited mTORC1 signaling. Mechanistically, we determined that sunitinib modulates MCL-1 stability by affecting its proteasomal degradation. Dual modulation of MCL-1 stability at different dose ranges of sunitinib was due to differential effects on ERK and GSK3β activity, and the latter also accounted for dual modulation of mTORC1 activity. Finally, comparison of patient samples prior to and following sunitinib treatment suggested that increases in MCL-1 levels and mTORC1 activity correlate with resistance to sunitinib in patients.
Quadruple Therapy with CsA, MTX, MMF and ATG and Triple Therapy with CsA, MTX and ATG for Preventing Graft-Versus-Host Disease in Unrelated Donor Hematopoietic Stem Cell Transplantation.
Authors: Zhiping Fan, Zhengshan Yi, Qifa Liu, Jing Sun, Dan Xu, Yu Zhang, Yongqiang Wei, Changxiong Ye
Journal: Blood (2005)
Online BCI typing using language model classifiers by ALS patients in their homes
Authors: William Speier, Nand Chandravadia, Dustin Roberts, Shrita Pendekanti, Nader Pouratian
Journal: Brain-Computer Interfaces (2016)

The P300 speller is a common brain-computer interface system that can provide a means of communication for patients with amyotrophic lateral sclerosis (ALS). Recent studies have shown that incorporating language information in signal classification can improve system performance, but this has largely been tested on healthy volunteers in a laboratory setting. The goal of this study was to demonstrate the functionality of the P300 speller system with language models when used by ALS patients in their homes. Six ALS patients with functional ratings ranging from 2 to 28 participated in this study. All subjects had improved offline performance when using a language model and five subjects were able to type at least six characters per minute with over 84% accuracy in online sessions. The results of this study indicate that the improvements in performance using language models in the P300 speller translate into the ALS population, which could help to make it a viable assistive device.
AB0134 Oxidative Stress Levels Are Increased in Systemic Lupus Erythematosus Patients with A Higher Accumulative Damage Score
Authors: E. Grau Garcia, M. Fernández Matilla, G. Poveda Marín, C. Feced Olmos, E. Labrador Sánchez, F.M. Ortiz Sanjuan, N. Fernández-Llanio, D. Hervás Marín, V. Fornes Ferrer, R. Rodrigo Nicolás, K. Arévalo Ruales, R. Negueroles Albuixech, J. Ivorra Cortés, J. Fragio Gil, I. Martínez Cordellat, J. Valero Sanz, I. Chalmeta Verdejo, L. González Puig, C. Alcañiz Escandell, C. Nájera Herranz, J. Castellano Cuesta, J. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Oxidative stress is increased in Systemic Lupus Erythematosus (SLE) patients, and contributes to the immune system imbalance, abnormal activation of apoptotic processes, autoantibodies production and the development of serious complications, such as cardiovascular comorbidities. <h3>Objectives</h3> To evaluate the influence of oxidative stress as an additional factor to the classical cardiovascular risk ones, in SLE patients. <h3>Methods</h3> Cross-sectional prospective study of SLE patients according to the SLICC-2012 criteria, coming from the Rheumatology Service of Arnau de Vilanova Hospital and La Fe Hospital. In all patients we analyzed the serum concentration of GS-Nem (GSH) and GSSG by UPLC-MS/MS (Acquity UPLC System). We have also taken healthy individuals as negative controls, who had the same blood-test. In patients was also made a complete blood-test, and clinical, treatment and biometric data were collected by personal interview. Biostatistical analysis was performed by the <i>R</i> software version 3.2.3., using a simple, binominal and logistic lineal regression. <h3>Results</h3> A total of 140 patients were evaluated; (95% women) with 33.39±13.63 year-old average at the diagnosis time with a 10.05± 11.42 year-evolution of SLE. We used GSH/GSSG ratio to assess the oxidative stress rate, being this value higher in patients than in healthy controls (P=0.005). We observed a statistically significant relationship between the presence of oxidative stress and accumulated damage assessed by SLICC-ACR (P&lt;0.0001). No differences according to the disease activity, specific autoimmune profile or by organ or systems affected. However, we found a slight difference in the GSH/GSSG ratio among patients who have had a CVD (1±0.39) and those who have not suffered CVD (1.19±0.55). No differences in the levels of oxidative stress are observed according to treatment with folic acid or the administration of biological therapies. <h3>Conclusions</h3> We observed increased levels of oxidative stress in our SLE patients compared to healthy controls. Data suggest a rise of oxidative stress in patients with a greater cumulative damage, which is consistent with the presence of severe comorbidities in these patients. It seems to be a slight tendency to increased oxidative stress levels measured with GSH/GSSG ratio in patients with SLE and cardiovascular involvement, but more independent studies are needed to confirm it. <h3>Disclosure of Interest</h3> None declared
Azacitidine in Myelodysplastic Syndromes: Multicenter Retrospective Study of 34 Long-Responder Patients
Authors: Carlo Finelli, Cristina Clissa, Maria Teresa Voso, Maria Antonietta Aloe Spiriti, Massimo Breccia, Gianluca Gaidano, Monica Crugnola, Maria Benedetta Giannini, Costanza Bosi, Virginia Naso, Matilde Y Follo, Sara Mongiorgi, Giovanni Martinelli, Lucio Cocco, Michele Baccarani
Journal: Blood (2012)
Thrombocytopoiesis Is Not Regulated by Thrombopoietin (TPO) but Proplatelet Formation (PPF) Stimulating Factor.
Authors: Kazunori Murai, Shugo Kowata, Yasuhiko Tsukushi, Mamiko Ishiguro, Tatsuo Oyake, Takeshi Sugawara, Yoji Ishida
Journal: Blood (2006)
The Treatment of Primary Mediastinal Large B-Cell Lymphoma: A Two Decades Monocentric Experience on 98 Patients
Authors: Beatrice Casadei, Alessandro Broccoli, Vittorio Stefoni, Cinzia Pellegrini, Letizia Gandolfi, Enrico Derenzini, Federica Quirini, Lisa Argnani, Pier Luigi Zinzani
Journal: Blood (2014)
AB0443 Relation Between Accumulative Damage and Disability Recogniced by The INSS* in Systemic Lupus Erythematosus Patients:
Authors: E. Grau Garcia, M. Fernández Matilla, G. Poveda Marín, C. Feced Olmos, E. Labrador Sánchez, F.M. Ortiz Sanjuan, N. Fernández-Llanio, D. Hervás Marín, V. Fornes Ferrer, K. Arévalo Ruales, R. Negueroles Albuixech, J. Ivorra Cortés, J. Fragio Gil, I. Martínez Cordellat, J. Valero Sanz, I. Chalmeta Verdejo, L. González Puig, C. Alcañiz Escandell, C. Nájera Herranz, J. Castellano Cuesta, J. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) in a multisystemic and autoimmune disease that specially affects young women during the second and third decade, and is able to injure different organs and or systems, being the most common one affected the musculoskeletal system. Events attributed to SLE itself and other related to the disease may impact negatively in the quality of life, unemployment, disability and mortality. Recent data show that 3.8% of SLE patients have comorbidities and 59.2% of them were receiving a disability pension. In Spain, the evaluation of disability and the assignation of the mentioned pension is given by the National Social Security Institute of Spain (INSS: Instituto Nacional de la Seguridad Social). <h3>Objectives</h3> To assess the relationship between cumulative damage regarding to the affected organ and the percentage of disability recognized by the INSS in SLE patients in Spain. <h3>Methods</h3> Cross-sectional prospective study of SLE patients according to the SLICC-2012 criteria, from the Rheumatology Service of Arnau de Vilanova Hospital and La Fe Hospital. We collected clinical and demographic data through personal interview and the SLIC-ACR questionnaire. <h3>Results</h3> A total of 140 patients were evaluated; of them, 95% were women with 33.39±13.63 year-old average at the diagnosis time with a 10.05±1.42 year-evolution of SLE. Clinical characteristics of each group are described in the table. <h3>Conclusions</h3> We observed a positive correlation between percentage of recognized disability and the SLICC-ACR index score. Musculoskeletal system is, in general, the most affected one, without differences between both groups; but we found a higher proportion of damage in nervous system, renal and vasculitis in patients with a recognized disability. <h3>Disclosure of Interest</h3> None declared
CD4+CD25+ Regulatory T Cells Enhance Immune Reconstitution Following Allogeneic Hematopoietic Cell Transplantation by Protecting Thymic and Lymphoid Compartments from Graft-Versus-Host Disease Damage without Impacting T Cell Repertoire Development.
Authors: Vu H. Nguyen, Daisy Chang, Sumana Shashidhar, Michael Bachmann, Christopher H. Contag, Janice M.Y. Brown, Robert S. Negrin
Journal: Blood (2006)
Impact of Killer Immunoglobulin Receptor (KIR) Ligand Incompatibility in Nonmyeloablative Bone Marrow Transplantation (BMT) from Haploidentical Donors.
Authors: Heather J. Symons, M. Sue Leffell, Nancy D. Rossiter, Elizabeth Sugar, Leo Luznik, Michele Phelps, Angelita Crawford, M. Yair Levy, Richard J. Jones, Ephraim J. Fuchs
Journal: Blood (2006)
AB0829 2012 American Guidelines for The Management of Gout as Seen by Family Doctors in France
Authors: C. Mourgues, M. Soubrier, B. Pereira, P. Vorilhon, S. Mathieu
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Gout is a common and potentially serious rheumatological disease. Its management in France remains inadequate, with target serum uric acid (SUA) levels being reached in 20% of cases. American guidelines for the management of gout were released in 2012. <h3>Objectives</h3> Our aim was to assess whether family doctors in Auvergne, France, agreed with the 14 recommendations for managing gout by mailing them a questionnaire. <h3>Methods</h3> An anonymous questionnaire was mailed to all the family doctors in our region in November 2014. <h3>Results</h3> The response rate was 40% (n=505/1263). Of the 505 family doctor respondents (FDRs), 60% had been in practice for more than 20 years. Some 56.2% were in practice in rural areas, and 53.6% followed on average 5 to 20 gout patients. Management of acute gout: 90.7% of FDRs agreed with pharmacological management within 24 hours of the attack; 95% of FDRs agreed with using colchicine, 72% short-course nonsteroidal anti-inflammatory drugs, and 16.6% corticosteroids; 81% approved of continuing hypouricemic therapy during the attack. Management of chronic gout: 61.6% agreed with not treating asymptomatic hyperuricemia. Allopurinol or febuxostat are used as the first-line therapies according to 88.7%. Half of respondents lowered target SUA when gout was tophaceous. <h3>Conclusions</h3> The guidelines generally met with the approval of family doctors in Auvergne (72% agreement). They were also confirmed on a European level in 2014. Their use should be disseminated with, however, some additional clarifications, particularly for the management of chronic gout. <h3>Disclosure of Interest</h3> None declared
Targeted case finding beats universal CVD screening, UK study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Targeting people at highest risk for cardiovascular disease (CVD) by estimating their cardiovascular risk score before screening is a more efficient and cheaper approach to primary prevention than the current strategy of health checks for all healthy adults, a modelling study analysing data from a UK primary care database has shown.1

Patients can be identified for primary prevention of CVD by universal screening or by assessing risk …
A Milestone Review on How Macrophages Affect Tumor Growth
Authors: Christophe Caux, Rodrigo Nalio Ramos, George C. Prendergast, Nathalie Bendriss-Vermare, Christine Ménétrier-Caux
Journal: Cancer Research (2016)

Visit the Cancer Research 75th Anniversary [timeline][1].

See related article by Lewis and Pollard, [Cancer Res 2006;66:605–12][2] .

In this 75th Anniversary issue commentary, we discuss a seminal review published in 2006 by Claire E. Lewis and Jeffrey W. Pollard in Cancer Research , entitled
PTH-149 A One Stop Iron Deficiency Anaemia Clinic: A Review of Its Efficacy
Authors: MS Lau, J Schembri, DS Sanders, JM Hebden
Journal: Gut (2016)

<h3>Introduction</h3> Iron deficiency anaemia (IDA) accounts for 4–13% of referrals to gastroenterology. A single consultant led one stop IDA clinic was set up to streamline all required tests (upper and lower gastrointestinal investigations, coeliac serology, intrinsic factor antibodies, immunoglobulins, urinalysis and ultrasound, or CT if appropriate) at the first clinic in order to reach a diagnosis quicker and reduce unnecessary follow ups. We aimed to evaluate the discharge rate after the first clinic visit compared to patients with IDA attending general gastroenterology clinics, and assess the patients’ compliance of haemoglobin (Hb) monitoring by general practitioners (GP) and response to iron post discharge to primary care. <h3>Methods</h3> We prospectively reviewed all cases referred with iron deficiency (IDA and isolated hypoferritanaemia) attending the clinic from 2013–14. The discharge rate after the first visit was analysed. We assessed the discharged patients’ response to iron at 3 or 6 months, defined by normalisation of Hb, excluding those with cancer. We reviewed their compliance with Hb monitoring at 3, 6, 9 and 12 months as advised by the consultant in clinic and also via letters to the GPs and patients, and compared it to that of patients who were followed up in clinic. <h3>Results</h3> A total of 214 iron deficient patients attended the clinic. The discharge rate was 90.2% (193/214) versus 26% for IDA patients attending general gastroenterology clinics (80% consultant led) in our previously published data in 2014. We excluded 24 patients with cancer, and 19 who did not have their Hb checked at 3 or 6 months, leaving 150 discharged patients for analysis. 51.3% (77/150) responded to iron therapy at 3 or 6 months. Of those, 68.8% (33/48) had a sustained response at 12 months after excluding 29 patients who did not have their Hb checked at 12 months. The compliance rate for Hb monitoring by the GP at 3, 6, 9 and 12 months in the discharged group was 24.9% (42/169), versus 9.5% (2/21) in the follow up group. <h3>Conclusion</h3> This one stop IDA clinic had a significantly higher discharge rate compared to general gastroenterology clinics for IDA patients. Half of the discharged patients had an initial response to iron, where two thirds of them had a sustained response at 12 months. It is unclear whether this was due to poor adherence to iron therapy or missed pathologies, however all patients underwent a comprehensive range of investigations. The compliance with Hb monitoring was low in both the discharge and follow up groups, suggesting that compliance was not necessarily related to whether the patient was followed up or discharged. Further emphasis is needed to relay the importance of Hb monitoring to both patients and GPs, in order to identify those who may require further investigations. <h3>Disclosure of Interest</h3> None Declared
High IKZF1/3 protein expression is a favorable prognostic factor for survival of relapsed/refractory multiple myeloma patients treated with lenalidomide
Authors: Maryam Pourabdollah, Mohammad Bahmanyar, Eshetu G. Atenafu, Donna Reece, Jian Hou, Hong Chang
Journal: Journal of Hematology & Oncology (2016)

The aim of this study is to assess nucleoprotein expression of IKZF1/3 in patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide-based therapy and correlated them with their clinical outcomes. A total of 50 patients diagnosed with MM were entered in the study with the median follow-up of 86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72 and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated with longer median progression free survival (P = 0.0029 and P < 0.0001) and overall survival (P = 0.0014 and P < 0.0001). IKZF3 expression also appears predicted a favorable response to the lenalidomide-based therapy.