tbuckley/cabot-search huggingface dataset:
AMPK–ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute Myeloid Leukemia Stem Cells
Authors: Ji Eun Jang, Ju-In Eom, Hoi-Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSC) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. Experimental Design: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34+CD38− leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations. Results: JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of beclin-1, increased LC3-II lipidation, formation of autophagosomes, and downregulation of p62/SQSTM1. Inhibition of autophagy by pharmacologic inhibitors or knockdown of beclin-1 using specific siRNA enhanced JQ1-induced apoptosis in resistant cells, indicating that prosurvival autophagy occurred in these cells. Independent of mTOR signaling, activation of the AMPK (pThr172)/ULK1 (pSer555) pathway was found to be associated with JQ1-induced autophagy in resistant cells. AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs. Conclusions: These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic strategy for combating resistance to BET inhibitors in AML and other types of cancer. Clin Cancer Res; 23(11); 2781–94. ©2016 AACR.
Impaired mucus clearance exacerbates allergen-induced type 2 airway inflammation in juvenile mice
Authors: Benedikt Fritzsching, Matthias Hagner, Lu Dai, Sandra Christochowitz, Raman Agrawal, Charlotte van Bodegom, Simone Schmidt, Jolanthe Schatterny, Stephanie Hirtz, Ryan Brown, Michelle Goritzka, Julia Duerr, Zhe Zhou-Suckow, Marcus A. Mall
Journal: Journal of Allergy and Clinical Immunology (2016)
Association of Risk Factors, Mortality, and Care Costs of Adults With Acute Myeloid Leukemia With Admission to the Intensive Care Unit
Authors: Anna B. Halpern, Eva Culakova, Roland B. Walter, Gary H. Lyman
Journal: JAMA Oncology (2016)

Adults with acute myeloid leukemia (AML) commonly require support in the intensive care unit (ICU), but risk factors for admission to the ICU and adverse outcomes remain poorly defined.To examine risk factors, mortality, length of stay, and cost associated with admission to the ICU for patients with AML.This study extracted information from the University HealthSystem Consortium database on patients 18 years or older with AML who were hospitalized for any cause between January 1, 2004, and December 31, 2012. The University HealthSystem Consortium database contains demographic, clinical, and cost variables prospectively abstracted by certified coders from discharge summaries. Outcomes were analyzed using univariate and multivariable statistical techniques. Data analysis was performed from November 15, 2013, to August 15, 2016.Primary outcomes were admission to the ICU and inpatient mortality among patients requiring ICU care. Secondary outcomes included length of stay in the ICU, total hospitalization length of stay, and cost.Of the 43 249 patients with AML (mean [SD] age, 59.5 [16.6] years; 23 939 men and 19 310 women), 11 277 (26.1%) were admitted to the ICU. On multivariable analysis (with results reported as odds ratios [95% CIs]), independent risk factors for admission to the ICU included age younger than 80 years (1.56 [1.42-1.70]), hospitalization in the South (1.81 [1.71-1.92]), hospitalization at a low- or medium-volume hospital (1.25 [1.19-1.31]), number of comorbidities (10.64 [8.89-12.62] for 5 vs none), sepsis (4.61 [4.34-4.89]), invasive fungal infection (1.24 [1.11-1.39]), and pneumonia (1.73 [1.63-1.82]). In-hospital mortality was higher for patients requiring ICU care (4857 of 11 277 [43.1%] vs 2959 of 31 972 [9.3%]). On multivariable analysis, independent risk factors for death in patients requiring ICU care included age 60 years or older (1.16 [1.06-1.26]), nonwhite race/ethnicity (1.18 [1.07-1.30]), hospitalization on the West coast (1.19 [1.06-1.34]), number of comorbidities (18.76 [13.7-25.67] for 5 vs none), sepsis (2.94 [2.70-3.21]), invasive fungal infection (1.20 [1.02-1.42]), and pneumonia (1.13 [1.04-1.24]). Mean costs of hospitalization were higher for patients requiring ICU care ($83 354 vs $41 973) and increased with each comorbidity, from $50 543 for patients with no comorbidities to $124 820 for those with 5 or more comorbidities.Admission to the ICU is associated with high mortality and cost that increase proportionally with the comorbidity burden in adults with AML. Several demographic factors and medical characteristics identify patients at risk for admission to the ICU and mortality and provide an opportunity for testing primary prevention strategies.
Multidrug Resistance Gene (MDR1) Polymorphisms May Serve as Predictors of Resistance to Imatinib in Chronic Phase Chronic Myeloid Leukemia Patients.
Authors: Simona Soverini, Sabrina Angelini, Eleonora Turrini, Alessandra Gnani, Sabrina Colarossi, Giovanni Perini, Ilaria Iacobucci, Patrizia Hrelia, Giorgio Cantelli Forti, Daniela Cilloni, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Thea Kalebic, Giovanni Martinelli
Journal: Blood (2007)
Comparison of Novel Markers in Prediction of Coronary Heart Disease Risk
Authors: Maryam Kavousi, Suzette Elias-Smale, Joost H. Rutten, Rozemarijn Vliegenthart Proenca, Matthijs Oudkerk, Moniek P. de Maat, Albert Hofman, Ewout Steyerberg, Anton H. van den Meiracker, Jacqueline C. Witteman
Journal: Circulation (2010)
Utility of PCR Amplification and DNA Microarray Hybridization in 16S rDNA for Rapid Diagnosis of Bacteremia Associated with Hematological Malignancies.
Authors: Eiju Negoro, Hiromichi Iwasaki, Katunori Tai, Satoshi Ikegaya, Mitsunobu Shimadzu, Takanori Ueda
Journal: Blood (2009)
Label-Free Raman Spectroscopy Detects Stromal Adaptations in Premetastatic Lungs Primed by Breast Cancer
Authors: Santosh Kumar Paidi, Asif Rizwan, Chao Zheng, Menglin Cheng, Kristine Glunde, Ishan Barman
Journal: Cancer Research (2016)

Recent advances in animal modeling, imaging technology, and functional genomics have permitted precise molecular observations of the metastatic process. However, a comprehensive understanding of the premetastatic niche remains elusive, owing to the limited tools that can map subtle differences in molecular mediators in organ-specific microenvironments. Here, we report the ability to detect premetastatic changes in the lung microenvironment, in response to primary breast tumors, using a combination of metastatic mouse models, Raman spectroscopy, and multivariate analysis of consistent patterns in molecular expression. We used tdTomato fluorescent protein expressing MDA-MB-231 and MCF-7 cells of high and low metastatic potential, respectively, to grow orthotopic xenografts in athymic nude mice and allow spontaneous dissemination from the primary mammary fat pad tumor. Label-free Raman spectroscopic mapping was used to record the molecular content of premetastatic lungs. These measurements show reliable distinctions in vibrational features, characteristic of the collageneous stroma and its cross-linkers as well as proteoglycans, which uniquely identify the metastatic potential of the primary tumor by recapitulating the compositional changes in the lungs. Consistent with histological assessment and gene expression analysis, our study suggests that remodeling of the extracellular matrix components may present promising markers for objective recognition of the premetastatic niche, independent of conventional clinical information. Cancer Res; 77(2); 247-56. ©2016 AACR.
PCSM-10THE END OF LIFE PHASE IN HIGH GRADE GLIOMA - A PROSPECTIVE ASSESSMENT OF SYMPTOMS
Authors: Tobias Walbert, Beverly Stallings, Joel Phillips
Journal: Neuro-Oncology (2015)

BACKGROUND: End-of-life (EoL) symptoms of patients have not been prospectively assessed in patients with high grade glioma (HGG). The aim of this study was to understand symptom progression and to define the EoL trajectory in HGG to make recommendations on palliative care or hospice involvement. METHODS: Prospective single-center study assessing symptoms and quality of life of HGG patients failing therapy with bevacizumab, showing clinical and radiological progression, and with a Karnofsky Performance Status score(KPS) <60. Patients and caregivers were enrolled. MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) and symptoms assessment was performed upon enrollment and bi-weekly thereafter by phone call. Follow-up continued until death. RESULTS: Data from 28 patient-caregiver dyads was available for interpretation. Fatigue, drowsiness, and concentration progressed significantly 12-14 weeks prior to death along with loss of appetite, change in bowel habits, and appearance. Seizures were rare but had severe impact if present. Remembering things, speaking and weakness was moderate at baseline and without significant progression. Loss of consciousness was reported in 19 patients with a median of 4 days (range 1-7) prior to death. Pain was mild throughout the disease course. Significant progressive interference in enjoyment of life, relationships, and work was observed. Hospice was initially contacted at a median of 3.5 weeks prior to death and enrollment took place within 1 week after initial contact in all but one patient. No patient received palliative care. All patients died under hospice care. DISCUSSION: This is the first prospective study of symptoms and quality of life in HGG patients. Our findings suggest that patients with HGG suffer from high morbidity in the EoL phase mainly due to fatigue, drowsiness, and concentration. Patients failing bevacizumab and presenting with a KPS ≤60 should be counselled about the possibility of hospice to assure proper symptom management and EoL decision making.
T Cell Receptor Gene Transfer to Virus-Specific T Cells for Cellular Anti-Tumor Immunotherapy.
Authors: Marieke Griffioen, H.M. Esther van Egmond, Menno A.W.G. van der Hoorn, Renate S. Hagedoorn, Michel Kester, Roelof Willemze, J.H. Frederik Falkenburg, Mirjam Heemskerk
Journal: Blood (2007)
FRI0022 Inflammatory Status and Serum Uric Acid Levels Determine High-Density Lipoprotein–Cholesterol Levels in A Non-Rheumatic Population: Table 1
Authors: M. Andrés, M.A. Quintanilla, P. Morillas
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In inflammatory disorders, highest incidence of cardiovascular (CV) events paradoxically occurs at lower lipid levels (1), especially in the case of high-density lipoprotein cholesterol (HDLc). Current data in general, non-inflammatory population suggest a similar but milder phenomenon (2). Serum uric acid (SUA) levels appear to determine the inflammatory status of the subjects, even in normouricemia (3). <h3>Objectives</h3> To assess whether inflammatory status and SUA levels associate with HDLc levels in a hypertensive population aged 65 years or older. <h3>Methods</h3> Retrospective analysis of the FAPRES study (cross-sectional study aimed at determining the prevalence of atrial fibrillation in hypertensive patients aged 65 years or older). Inflammatory status was considered based on serum leukocytes levels. A comparison between serum lipids levels (HDLc, low-density lipoprotein-cholesterol [LDL], total cholesterol [TCh], triglycerides [TG]) and different tertiles of leukocytes and SUA has been performed using ANOVA. In case of statistically significant differences, a multivariate linear regression model was built for each lipid parameter in order to adjust for potential confounders. <h3>Results</h3> A total of 1,003 patients were recruited, mean aged 72.9 years (SD±5.8), 52.5% females. In the sample median (±SD) leukocytes, SUA and HDLc were 6,719.6/mm<sup>3</sup> (±1773.1), 5.2 mg/dL (±1.1), and 52.8 mg/dL (±13.1), respectively. Table shows the distribution of lipids across leukocytes and SUA tertiles: lower HDLc and higher TG levels were found in upper tertiles of both leukocytes and SUA, with no differences on TCh and LDLc. After adjusting for potential confounder (age, gender, CV risk factors, renal failure, body mass index, use of diuretics or statins), an independent, inverse association of both leukocytes (β=-0.001, p=0.02) and SUA (β=-1.054, p=0.03) with HDLc levels was confirmed. For TG levels, an independent, direct association with SUA (β=8.254, p=0.004) was also found, as well as a trend for leukocytes (β=0.003, p=0.06). <h3>Conclusions</h3> In a non-rheumatic, hypertensive population aged 65 years or older, both inflammatory status and SUA levels showed an inverse, independent association with HDLc, following current data on patients with inflammatory disorders. This phenomenon might help to define a pro-atherogenic profile on the general population. <h3>References</h3> Ann Rheum Dis 2011;70:482. Circulation 2003;107:391. Eur Heart J 2006;27:1174. <h3>Disclosure of Interest</h3> None declared
DCEP (Dexamethasone, Cyclophosphamide, Etoposide, Cisplatin) Followed by High-Dose G-CSF Is a Highly Efficient and Safe Regimen for Stem Cell Mobilization for Multiple Myeloma.
Authors: Jason P. Gonsky, Nikoletta Lendvai, Michele L. Donato, Scott D. Rowley, Andrew L. Pecora, Tatyana Feldman, Andre Goy, Stuart Goldberg, David S. Siegel
Journal: Blood (2007)
Engineering a "Self-Healing" Hydrogel-Based Microvasculature-on-a-Chip for Investigating the Effects of Cellular and Biomolecular Interactions on Endothelial Permeability in Sickle Cell Disease
Authors: Yongzhi Qiu, Byungwook Ahn, Yumiko Sakurai, Caroline Hansen, Clinton H. Joiner, Solomon Fiifi Ofori-Acquah, Wilbur A Lam
Journal: Blood (2015)
SP0065 Immunosuppressive Activities of B Cells and Plasma Cells
Authors: S. Fillatreau
Journal: Annals of the Rheumatic Diseases (2016)

B cells can contribute to immunity through production of antibodies, presentation of antigen to T cells, and secretion of cytokines. Through these mechanisms, B cells can act both as drivers and as regulators of immunity, and these two antagonistic activities seem to be at play during the majority of immune responses. Understanding how these opposite functions are mediated shall stimulate the elaboration of novel approaches for monitoring and manipulating the immune system. Here, we will discuss specifically about how B cells negatively regulate immunity through provision of cytokines. The presentation will discuss the suppressive roles of B cells during autoimmune disorders, and infectious diseases. The signals controlling the acquisition of suppressive functions by B cells (BCR, TLR, CD40), the mediators of suppression (production of IL-10 and IL-35), and the mechanisms of suppression (effects on innate cells, effector and regulatory T cells) will be presented. Moreover, we will discuss the phenotype of the B cells providing these regulatory functions <i>in vivo</i>, emphasizing the concept that specific subsets of plasma cells/plasmablasts are the major B cell source of regulatory IL-10 and IL-35 <i>in vivo</i>. <h3>Disclosure of Interest</h3> None declared
Sunitinib and Intensive Chemotherapy in Patients with Acute Myeloid Leukemia and Activating FLT3 Mutations: Results of the AMLSG 10-07 Study (ClinicalTrials.gov No. NCT00783653)
Authors: Walter Fiedler, Sabine Kayser, Maxim Kebenko, Jürgen Krauter, Helmut R. Salih, Katharina Götze, Daniela Späth, Gudrun Göhring, Veronica Teleanu, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Richard F Schlenk
Journal: Blood (2012)
Hsp70 Is a New Major Regulator of Erythropoiesis by Preventing Caspase-3-Mediated Cleavage of GATA-1.
Authors: Jean-Antoine X. Ribeil, Yael Zermati, Joelle Kersual, Michael Dussiot, Francoise Audat, Cecile Pouzet, Francoise Valensi, Bruno Varet, Eric Solary, Carmen Garrido, Olivier Hermine
Journal: Blood (2004)
SAT0497 Epidemiological Study of Infectious Spondylitis in A Tunisian Center: about 118 Cases
Authors: K. Baccouche, N. Elamri, S. Belghali, M. Bouzaoueche, H. Zeglaoui, E. Bouajina
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Infectious spondylitis remains frequent in Tunisia and is a common reason for hospitalization in rheumatology. We report the experience of our rheumatology department in the diagnosis and management of infectious spondylitis. <h3>Methods</h3> This is a retrospective study of 118 cases of infectious spondylitis observed between 1997 and 2015. The diagnosis was based on clinical, biological, radiological and bacteriological data. <h3>Results</h3> Our population consisted of 76 men (64.4%) and 42 women (35.6%) with a mean age of 59.2 years [18–84]. A supporting ground was found in 27% of patients. This was diabetes in 17.8% of cases, extra-articular history of tuberculosis in 7.6% of cases, hemodialysis for renal failure in 2.5% of cases, recent spinal surgery in 3.4% of cases, visceral surgery in 2.5% of cases and a long-term corticosteroid in 1.2% of cases. Spinal pain was present in all cases and had an inflammatory rhythm in 89.8% of cases. Fever was observed in 48.3% of cases, night sweats in 27.1% of cases and impaired general condition in 50% of cases. Neurological signs, present in 55.9% of cases were: radiculalgia in 55.1% of cases, motor deficit in 20.3% of cases and spinal cord compression in 9.3% of cases. The inflammatory syndrome was absent in 10.2% of cases. Spinal MRI and CT performed respectively in 77% and 47.4% of cases showed an epidural in 52.5%, a soft tissue abscess in 34.7%, soft tissue infiltration in 27.9% and a root canal abscess in 14.4% of cases. The spondylitis was multifocal in 7.7% and multi-stage in 11% of cases. Affected levels were: lumbar spine in 66.6%, the thoracic level in 26.9% and the cervical level in 8.5% of cases. The germ was isolated in 53.5% of cases. The disco-vertebral biopsy (performed in 42.3% of cases) was contributory in 27.2% of cases. A puncture of a soft tissue abscess (formed in 14.1% of cases) was contributory in 85.9% of cases. Blood cultures were positive in 7.7% of cases. The urine culture had found the germ in 6.4% of cases and a skin sample in 1.2% of cases. Wright serology was positive in 20.5% of cases. These germs were: tuberculosis in 44.9% of cases, brucellosis in 20.5% and pyogenic germs in 29.5% of cases. <h3>Conclusions</h3> The clinical presentation of infectious spondylitis is polymorphic and determination of the causative organism can be difficult. In our series, in most cases it was a spondylodiscitis -specific germ. Support by appropriate antibiotic therapy leads overall to a good clinical outcome. Neurological complications can regress, more rarely from is fatal. <h3>Disclosure of Interest</h3> None declared
THU0309 Low-Dose Aspirin as Primary Prophylaxis for Cardiovascular Events in Systemic Lupus Erythematosus: A Long-Term Follow Up
Authors: S. Fasano, M. Iudici, I. Pantano, L. Pierro, G. Valentini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cardiovascular (CV) morbidity and mortality are significantly greater in Systemic Lupus Erythematosus (SLE) patients than in the general population. Acetylsalicylic acid (ASA) is known to be associated with a decrease in the incidence of CV events in high-risk patients from general population [1]. <h3>Objectives</h3> We previously investigated ASA efficacy as primary prophylaxis in 167 SLE patients followed for 7 patient-years [2]. Here, we report data collected in 189 patients followed for 8,2 patient-years. <h3>Methods</h3> SLE patients consecutively admitted to a tertiary center, who, at admission, satisfied 1992 ACR and/or 2012 SLICC classification criteria for SLE and had not experienced any CV event, were enrolled into the study. Low-dose ASA (100 mg/day) was prescribed to each patient at first visit. Fourteen patients (7%) refused to take it. At each 6-monthly visit, ASA side effects, ASA discontinuation and occurred CV events were recorded. <h3>Results</h3> 189 consecutive SLE patients were followed-up for a median of 8 years (range 1–15). Among them, 164 regularly took the medication (ASA-treated) and 25 refused to take or discontinued it (non-ASA-treated patients). Six CV events occurred in the 164 ASA-treated (4.2/1000 person-years), 4 in the 25 non-ASA-treated patients (25.4/1000 person-years) (p=0.003). No relevant side effect related to ASA treatment was recorded. <h3>Conclusions</h3> Present data further support the role of ASA in the primary prophylaxis of CV events in SLE patients. <h3>References</h3> Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2012;141 Iudici M, Fasano S, Gabriele Falcone L, et al. Low-dose Aspirin as Primary Prophylaxis for Cardiovascular Events in Systemic Lupus Erythematosus: A Long-Term Retrospective Cohort Study. Rheumatology (Oxford) Submitted for publication. <h3>Disclosure of Interest</h3> None declared
Bicarbonate Balance and Prescription in ESRD
Authors: Matthew K. Abramowitz
Journal: Journal of the American Society of Nephrology (2016)

The optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.
Evaluation of Two Secondary Prophylaxis Regimens of Recombinant Factor IX(r-IX) in Moderately Severe to Severe( FIX ≤2%) Hemophilia B Patients
Authors: Pablo Rendo, Mary-Kate Barrette-Grischow, Lynne Smith, JM Korth-Bradley, Robert Charnigo, Frank E. Shafer
Journal: Blood (2012)
Bending the blood pressure curve down: are we succeeding?
Authors: Kazem Rahimi
Journal: The Lancet (2016)

Until just a few decades ago, raised blood pressure was regarded as a benign and natural process of ageing that did not warrant treatment. In the 1966 edition of his textbook Diseases of the Heart,1 the cardiologist Charles Friedberg noted that treatment of individuals with a blood pressure lower than 200/100 mm Hg was not indicated. Since then, the accumulation of a large body of evidence on raised blood pressure has fundamentally changed clinical practice and health policy worldwide. Large-scale epidemiological studies2 have proven beyond doubt that long-term exposure to raised blood pressure is associated with a substantially increased risk of cardiovascular disease, with no apparent benign range at any age.
Anti-EGFR Antibody Cetuximab in Refractory or Relapsed Multiple Myeloma: Preliminary Results and Evaluation of Response Prediction in a Phase II Clinical Trial
Authors: Bastian von Tresckow, Denissa Peine, Boris Böll, Dennis A Eichenauer, Elke Pogge von Strandmann, Stefan Knop, Marielle Goebeler, Michael Hallek, Andreas Engert, Kai Hübel
Journal: Blood (2008)