tbuckley/cabot-search huggingface dataset:
Expression and processing analyses of wild type and p.R47H TREM2 variant in Alzheimer’s disease brains
Authors: Li Ma, Mariet Allen, Nobutaka Sakae, Nilufer Ertekin-Taner, Neill R. Graff-Radford, Dennis W. Dickson, Steven G. Younkin, Daniel Sevlever
Journal: Molecular Neurodegeneration (2016)

Genetic analyses showed that the triggering receptor expressed in myeloid cells 2 (TREM2) p.R47H variant increases the risk for Alzheimer's disease (AD). The question of whether the p.R47H mutation affects expression or function of the receptor remains unanswered. To address this question we quantified mRNA and analyzed protein profiles of WT and p.R47H TREM2 in human brains. Quantitative real-time PCR (qPCR) was performed using 2 sets of primers one that detects all TREM2 mRNA isoforms and one specific for the alternative spliced isoform (TREM2alt) that encodes for the extracellular domain (soluble TREM2). Because in the brain TREM2 is expressed primarily in microglial cells, we also assessed the levels of IBA1 to control for microglial variability across samples. For TREM2 protein quantitation and N-glycosylation processing, RIPA brain extracts were analyzed by Western blot before and after EndoH and PNGaseF treatments. We identified statistically significant increased levels of TREM2 transcripts in the temporal cortex of AD subjects when compared with controls; TREM2alt was likewise higher in AD cases, but was not significant after adjustment for covariates. Quantitative analysis of TREM2 protein confirmed qPCR results that showed higher levels in AD than in control brains. Among AD subjects, we observed a trend towards higher mRNA and protein TREM2 levels in carriers of the p.R47H risk allele. Analysis of individual TREM2 species found no difference in the relative amounts of mature and immature species, and carboxyl terminal fragments between non carriers and p.R47H samples. Furthermore, TREM2 species from either non carriers or p.R47H brains were equally susceptible to EndoH and PNGaseF treatments. Our results suggest that TREM2 expression is increased in AD. Furthermore, we provide evidence indicating that p.R47H mutation does not affect the levels of TREM2 either directly by altering expression or indirectly by affecting processing of the protein. Our data support previous findings that suggest that p.R47H variant affects TREM2 function by altering binding properties of the receptor rather than expression.
Hyperkalemia, Sacubitril/Valsartan, and Mineralocorticoid Antagonists in Patients With Heart Failure
Authors: Justin A. Ezekowitz
Journal: JAMA Cardiology (2016)

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Targeting Stromal Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth
Authors: Lifeng Yang, Abhinav Achreja, Tsz-Lun Yeung, Lingegowda S. Mangala, Dahai Jiang, Cecil Han, Joelle Baddour, Juan C. Marini, Joseph Ni, Ryuichi Nakahara, Stephen Wahlig, Lisa Chiba, Sun Hye Kim, Joshua Morse, Sunila Pradeep, Archana Sidalaghatta Nagaraja, Monika Haemmerle, Noh Kyunghee, Mathew Derichsweiler, Thomas Plackemeier, Imelda Mercado-Uribe, Gabriel Lopez-Berestein, Tyler Moss, Prahlad T. Ram, Jinsong Liu, Xiongbin Lu, Samuel C. Mok, Anil K. Sood, Deepak Nagrath
Journal: Cell Metabolism (2016)
Calciprotein particles as potential etiologic agents of idiopathic preterm birth
Authors: Lydia L. Shook, Catalin S. Buhimschi, Antonette T. Dulay, Megan E. McCarthy, John T. Hardy, Christina M. Duzyj Buniak, Guomao Zhao, Irina A. Buhimschi
Journal: Science Translational Medicine (2016)

Aggregation of calciprotein particles in amniotic fluid may play a pathogenic role in idiopathic preterm birth.
The ACCURE-UK trial: The effect of appendectomy on the clinical course of ulcerative colitis – A feasibility study
Authors: D. Nepogodiev, R. Howard, S. Pathmakanthan, T. Iqbal, B. Singh, Y. Oo, J. Mathers, C. McMullan, S. Sahamai, J. Gath, L. Magill, K. Handley, J. Deeks, W. Bemelman, D. Morton, T. Pinkney
Journal: International Journal of Surgery (2016)
Prognostic Value of ZAP-70 Expression Detected by Immunohistochemistry on Bone Marrow Biopsies in Early Phase Chronic Lymphocytic Leukaemia.
Authors: Achille Ambrosetti, Roberta Zanotti, Marco Chilosi, Flavia Zanetti, Maurizio Lestani, Cristian Pattaro, Andrea Remo, Omar Perbellini, Giovanni Pizzolo
Journal: Blood (2004)
MLL Rearrangement and Age At Diagnosis Are Strongly Associated with High Level Surface FLT3 Expression and Ex Vivo Sensitivity to FLT3 Inhibition: A Prospective Analysis of 54 Consecutive Infants with ALL Enrolled in Children's Oncology Group (COG) Trial AALL0631
Authors: Allison J. Kaeding, Daniel Magoon, Yarden Fraiman, Tamekia Jones, Nyla A. Heerema, Andrew J. Carroll, Kathleen W. Rao, Joanne M. Hilden, Stephen P. Hunger, Donald Small, Patrick A. Brown
Journal: Blood (2011)
Role for BH3-Only Protein NOXA In Growth-Factor Deprivation and Early Erythropoiesis
Authors: Christian R. Geest, Felix M. Wensveen, Sten F.W.M. Libregts, Alex M. de Bruin, Ingrid A.M. Derks, Paul G. Ekert, Verena Labi, Andreas Villunger, Martijn A. Nolte, Eric Eldering
Journal: Blood (2010)
Comparison of T Cell (CD3+) Chimerism after Myeloablative (MY) and Nonmyeloablative (NM) Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT).
Authors: Ronald Sobecks, Karl Theil, Lisa Rybicki, Jennifer Bates, Matt Kalaycio, Steven Andresen, Brad Pohlman, Robert M. Dean, John William Sweetenham, Laura Bernhard, Kelly Cherni, Mary Serafin, Karen Sands, Jennifer Kosar, Brian J. Bolwell
Journal: Blood (2006)
High Remission Rates and Long-Term Survival in a High Percentage of Patients Achieved by Intensive Chemotherapy for AML and Further Improvement of Supportive Care.
Authors: Taiichi Kyo, Akiko Kimura, Kouhei Kyo, Noriaki Yoshida, Hideki Asaoku, Koji Iwato, Yuuta Katayama, Hiromi Yuasa
Journal: Blood (2009)
Proteomic Screening Applied to the Diagnosis of Chronic Graft-Versus-Host-Disease.
Authors: Eva M. Mischak-Weissinger, Michael Stadler, Ernst Holler, Michael Schleuning, Hildegard Greinix, Hans-Jochem Kolb, Anne M Dickinson, Annika Krons, Helmut Diedrich, Julia Kontsendorn, Norbert Hahn, Jochen Metzger, Arnold Ganser
Journal: Blood (2009)
Clinical Relevance of Molecular Markers in Taiwan Chinese Patients with Primary Myelofibrosis: Endogenous Erythroid Colony Growth Is the Most Important Predictor of Outcomes
Authors: Ming-Chung Kuo, Tzung-Chih Tang, Tung-Liang Lin, Po-Nan Wang, Po Dunn, Jin-Hou Wu, Hung Chang, Tung-Huei Lin, Chia-Hui Chang, I-Jung Wu, Lee-Yung Shih
Journal: Blood (2015)
AB0414 Mycophenolate Mofetil and Deflazacort in Neuropsychiatric Lupus: A Retrospective Study
Authors: N. Gupta, S.K. Mandal, J. Mathew, S. Pulukool, R. Goel, A.J. Mathew, A. Nair, T. Sebastian, D. Danda
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Mycophenolatemofetil (MMF) is an effective therapeutic agent with high safety profile in the management of lupus nephritis. <h3>Objectives</h3> This retrospective study was conducted to assess the efficacy and side effect profile of MMF and deflazacort in patient with neuropsychiatry lupus (NP SLE). <h3>Methods</h3> Patients of SLE by SLICC 2012 between January 2005 and May 2015 satisfying ACR 1997 criteria for NP SLEwere recruited from department of Clinical immunology &amp; Rheumatology, Christian Medical College, Vellore, India. Patients consistently using MMF as the second line agent were enrolled. Clinical response, SLEDAI and side effect profile were noted from electronic medical records. Clinical improvement was defined as remission of presenting neurological symptom with no new neurological symptom. <h3>Results</h3> Of the 140 patients with NP SLE, 88 fulfilled the inclusion criteria. Mean age of the cohort was 25.51±7.82 years with female to male ratio of 84: 4. Median duration of neurological symptoms prior to presentation was 90 (17.5 – 317.5) days. Median duration of follow up was 33 (3–129) months. Among the various NP SLE manifestations, seizure was the most common presentation (n=37, 42.05%). Renal involvement was seen in 49 (55.7%) patients. MRI findings varied from white and grey matter hyper -intensities to ventricular dilatation and brain atrophy. Of the 88 patients on MMF, 13 were pulsed with 1 gm methylprednisolone for 3 days and 8 were pulsed with oral dexamethasone pulse of 40 mg/day for 5 days. Subsequently, oral steroids was started at a dose of 1 mg/kg &amp; tapered after 8–12 weeks to mean deflazacortdose (prednisoloneeqyuivalent) of 11.07±7.77 (9.33±5.88) mg at the end of 1 year. IMAGE: Showing various parameters at baseline and follow up as below. Major adverse events included lower respiratory tract infection in 2 patients and 1 fatality due to sepsis from gastroenteritis. Of 68 patient with median duration of follow up of 33 (3–129) months, 17 were only on MMF without any steroids, 14 not on either steroids or MMF and 6 were only on maintenance low dose steroids. Deflazacort was equally efficacious and had better toxicity profile than prednisolone. <h3>Conclusions</h3> In patients of NP SLE, MMF is efficacious in inducing remission and preventing relapse of disease with a good safety profile. Deflazacort was found to have superior toxicity profile with equal efficacy as to prednisolone in NP SLE patients. <h3>Disclosure of Interest</h3> None declared
Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease
Authors: W. Schuyler Jones, Iris Baumgartner, William R. Hiatt, Gretchen Heizer, Michael S. Conte, Christopher J. White, Jeffrey S. Berger, Peter Held, Brian G. Katona, Kenneth W. Mahaffey, Lars Norgren, Juuso Blomster, Marcus Millegård, Craig Reist, Manesh R. Patel, F. Gerry R. Fowkes
Journal: Circulation (2016)

Background: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. Results: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98–1.23, P =0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08–1.55, P =0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86–6.25, P &lt;0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88–1.15; P =0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86–1.15; P =0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78–1.36; P =0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83–1.59; P =0.41). The median duration of follow-up was ≈30 months. Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01732822.
Overexpression of BAALC and MN1 Predict Worse Outcome in De Novo AML with Partial Tandem Duplication of MLL.
Authors: Tung-Liang Lin, Lee-Yung Shih, Der-Cherng Liang, Chein-Fuang Huang, Chia-Hui Chang, Ming-Chung Kuo, Chang-Liang Lai, Tung-Huei Lin
Journal: Blood (2009)
Targeting the Clonogenic Side Population of Multiple Myeloma by Immunomodulatory Drugs (IMiDs) in the Context of Stromal Cell Microenvironment: Pathophysiologic and Clinical Implications.
Authors: Jana Jakubikova, David N. Cervi, John F. Daley, Danka Cholujova, Melissa G. Ooi, Steffen Klippel, Simona Blotta, Merav Leiba, Jake Delmore, Douglas McMillin, Efstathios Kastritis, Jacob Laubach, Paul Richardson, Jan Sedlak, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Blood (2009)
Histopathologic and Molecular Features of Persistent Polyclonal B-Cell Lymphocytosis Challenging the Benign Nature of the Disorder.
Authors: Ilaria Del Giudice, Stefano A. Pileri, Maura Rossi, Elena Sabattini, Cristina Campidelli, Irene Della Starza Miss, Stefania M. De Propris, Francesca Mancini, Francesca R. Mauro, Agostino Tafuri, Luisa Bizzoni, Angela Rago, Angela Amendola, Anna Guarini, Robert Foa
Journal: Blood (2006)
BMET-16GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES USING ONLY 3 PINS
Authors: Jennifer C. Ho, Dershan Luo, Nandita Guha-Thakurta, Sherise D. Ferguson, Amol J. Ghia, James N. Yang, Paul D. Brown, Khinh Ranh Voong
Journal: Neuro-Oncology (2015)

OBJECTIVE: Removal of a pin during Gamma Knife® stereotactic radiosurgery (GK_SRS) may be necessary to prevent collision and allow for treatment. We investigated outcomes following GK_SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins. MATERIALS/METHODS: Between 2009-2014, we retrospectively reviewed the records of 1,971 patients and identified 20 patients with multiple brain metastases treated with GK_SRS in which 1 anterior pin was removed immediately before treatment of a single posteriorly located lesion. GK_SRS was also delivered to 121 other lesions using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival. Characteristics were compared using the Wilcoxon rank sum and Fisher's exact tests. Survival was analyzed using the Kaplan-Meier method. RESULTS: The median number of lesions treated per session was 6 (range 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or cerebellum (n = 6). Median follow-up was 12.3 months. There was one local failure of a control lesion. Lesions treated using 3 pins had a lower prescription isodose line, and gradient index. GK_SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage. CONCLUSION: Treating posteriorly located brain metastases with GK_SRS using only 3 pins provides excellent local control and no difference in treatment toxicity, making it a safe and reasonable option for lesions that may otherwise not be possible to treat.
Pharmacodynamic Study of Phase 1/2 Trial of the XIAP Antisense Oligonucleotide (AEG35156) in Combination with Chemotherapy in Patients with Relapsed/Refractory AML.
Authors: Bing Z. Carter, Duncan H. Mak, Stephen Morris, Gautam Borthakur, Elihu Estey, Anna L. Byrd, Marina Konopleva, Hagop M. Kantarjian, Michael Andreeff
Journal: Blood (2008)
PWE-085 Characterising Nocturnal and Daytime Gord Using Oesophageal High Resolution Manometry; A Retrospective Study
Authors: RS Heer, S Jiang, T Wong, S Alavi, J Jafari
Journal: Gut (2016)

<h3>Introduction</h3> Patients suffering from gastro-oesophageal reflux disease (GORD) can be categorised into those suffering from a purely daytime (DAY), purely nocturnal (NOCT) or combined reflux pattern. Despite identifying a dominant pattern of reflux the treatment strategies are not specifically targeting a specific type reflux pattern. This may expose patients to treatments which may not necessarily be beneficial to that particular pattern of reflux. Possible factors affecting different patterns of reflux may include abnormal oesophageal motility, lower oesophageal sphincter (LOS) length, presence of a hiatus hernia or too short of a time gap between meal and sleep. We aimed to determine the mechanisms behind patients suffering from purely nocturnal reflux compared to purely daytime reflux. <h3>Methods</h3> Patients who underwent High Resolution Manometry (HRM) in an outpatients clinic from December 2014 to November 2015 were retrospectively grouped into those with purely nocturnal reflux and those with purely daytime reflux as measured by 24 hour ambulatory pH-impendance monitoring. Comparisons were made between the two groups using Fisher’s exact tests and receiver operating characteristic (ROC) curves for LOS baseline pressure, LOS length, meal-sleep time gap, presence of a hiatus hernia, oesophageal motility disorders, age and gender. A P value &lt;0.05 was considered as significant. <h3>Results</h3> 62 patients with purely nocturnal reflux (median age 46.5, 27 male) and 32 patients with purely daytime reflux (median age 60, 15 male) were included. HRM diagnosis were not significantly different between these two groups (53% ineffective oesophageal motility (IOM) in NOCT and 50% IOM in DAY patients, P = 0.8). There was also no significant difference between the two groups in terms of prevalence of a hiatus hernia (P = 0.4), LOS length (P = 0.1), LOS mean or min baseline pressure (P = 0.6 for both). However, the meal-sleep time gap appeared to be significantly different between the DAY and NOCT group (148 ± 18 min in DAY vs 107 ± 9 min in NOCT, P = 0.03). Also, younger patients showed a significantly higher rate of nocturnal reflux (&lt;48 year old, had more chance of being NOCT, sensitivity 53%, specificity 79.4%, P = 0.009). <h3>Conclusion</h3> In this study we did not find any manometric parameter to be significantly predictive of being a NOCT or DAY patient. Nevertheless, further study is required to explore in more detail the effect of age on pattern of GORD. Previous literature have demonstrated the effect of the meal-sleep time gap which is also confirmed in this study. <h3>Disclosure of Interest</h3> None Declared
Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab
Authors: Nizar S. Abdelfattah, Mayss Al-Sheikh, Sean Pitetta, Ahmed Mousa, SriniVas R. Sadda, Charles C. Wykoff, Charles C. Wykoff, Daniel E. Croft, David M. Brown, Rui Wang, John F. Payne, Lloyd Clark, Nizar Saleh Abdelfattah, SriniVas R. Sadda, Matthew S. Benz, Eric Chen, Richard H. Fish, David L. Johnson, Rosa Y. Kim, James C. Major, Ronan E. O'Malley, Amy C. Schefler, Ankoor R. Shah, Sushma K. Vance, John A. Wells, Tien P. Wong
Journal: Ophthalmology (2016)
Extra-Nuclear Dislocation of PU.1 but Not CEBPA by Mutated NPM1 in AML Explains Lineage-Associations, ATRA Therapeutic Potential and DNMT3A Secondary Mutation.
Authors: Xiaorong Gu, Reda Z Mahfouz, Zhenbo Hu, Yogenthiran Saunthararajah
Journal: Blood (2012)
Renal Complications after Busulfan-Based Reduced-Intensity Stem Cell Transplantation in 286 Patients with Hematological Disorders.
Authors: Kimikazu Yakushijin, Takahiro Fukuda, Yoshitaka Asakura, Saiko Kurosawa, Nobuhiro Hiramoto, Daisuke Nakamura, Kohei Tada, Masaaki Nishinohara, Akihito Hagiwara, Niina Ueno, Yutaro Kamiyama, Masakazu Mori, Sung-Won Kim, Shin-ichiro Mori, Ryuji Tanosaki, Yuji Heike, Yoichi Takaue
Journal: Blood (2009)
Bcr-Abl Impairs T Cell Development From Murine Induced Pluripotent Stem Cells and Hematopoietic Stem Cells; A Partial Explanation for the Concept That Ph+ Clone Never Involves T Cell Lineage in CML,
Authors: Bidisha Chanda, Kiyoko Izawa, Ratanakanit Harnprasopwat, Keisuke Takahashi, Seiichiro Kobayashi, Yumi Kanegae, Izumu Saito, Arinobu Tojo
Journal: Blood (2011)
Long-Term Follow-up of Rituximab and Infusional Cyclophosphamide, Doxorubicin, and Etoposide (cde) in Combination with HAART in HIVRelated Non-Hodgkin’s Lymphomas (NHL).
Authors: Michele Spina, Cecilia Simonelli, Emanuela Vaccher, Ulrich Jaeger, Joseph Sparano, Renato Talamini, Umberto Tirelli
Journal: Blood (2008)
Idelalisib Given Front-Line for the Treatment of Chronic Lymphocytic Leukemia Results in Frequent and Severe Immune-Mediated Toxicities
Authors: Benjamin L Lampson, Tiago Matos, Haesook T. Kim, Siddha Kasar, Elizabeth A. Morgan, Masahiro Hirakawa, Joshua Fein, Stacey M. Fernandes, Jerome Ritz, Jennifer R. Brown
Journal: Blood (2015)
AB0689 Comoparison between Males and Females with Spondyloarthritis
Authors: J. Essouiri, N. Benaicha, F.E. Abourazzak, T. Harzy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> The aim of our study is to describe the characteristics of women with spondyloarthritis though a comparison with men. <h3>Methods</h3> This is a retrospective observational study, conducted in the rheumatology department at CHU Hassan II Fez, analyzing the records of patients diagnosed spondyloarthritis during the period extending from January 2009 to June 2014. We realized a descriptive study of our patients then we compared clinical and epidemiological profil of spondyloarthritis in both sex to emphasize the characteristics of morrocan women spondyloarthritis. <h3>Results</h3> A 136 patients were included, 86 men and 50 women. The mean age was 38,44±13,5 years with an average diagnostic delay of 4,71±5 years. Clinical symptomatology was dominated by axial involvement dorsolombalgie in 90,4% of cases. Uveitis was the extra-articular manifestation most common in 5,1% of cases. 61,8% of patients had active disease, and 46,3% had severe disease.10,3% of patients had juvenile-onset, 24.1% patients had a hip involvement. The comparison of women and men objectified significant association between female sex and late onset of disease (p&lt;0,001), illiteracy (p=0,021), family antecedent of spondyloarthrtitis (p=0,025), arthritis (p=0,049), the use of sulfasalzine and methotrexate (p=0,042, p=0,006 respectively) After logistic regression analysis the female sex was associated with late onset of disease (p&lt;0,001, OR=0,93; IC=0,89–0,96) and the use of methotrexate (p=0,018, OR=0,14;IC=0,02–0,71) whereas male sex was associated with hip involvement (p=0,02, OR=3,3; IC=1,18–13,03) and tabac (p=0,004, OR=22,47; IC=2,76–182) <h3>Conclusions</h3> Women with AS appear to have both similarities and differences in disease expression when compared with men with spondyloarthritis. The causes of the differences are still unknown, although both sex and gender factors may explain some of them. <h3>Disclosure of Interest</h3> None declared