tbuckley/cabot-search huggingface dataset:
NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes
Authors: Alexander J.A. Deutsch, Beate Rinner, Martin Pichler, Katharina Prochazka, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Krogsdam, Heinz Sill, Gerhard G. Thallinger, Hildegard T. Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Journal: Cancer Research (2017)

Abstract Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas. Cancer Res; 77(9); 2375–86. ©2017 AACR.
A Correction to the Research Article Titled: "Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens" by Brian Alexander, Jennifer Warner-Schmidt, Therese Eriksson, Carol Tamminga, Margarita Arango-Lievano, Subroto Ghose, Mary Vernov, Mihaela Stavarache, Sergei Musatov, Marc Flajolet, Per Svenningsson, Paul Greengard, Michael G. Kaplitt
Journal: Science Translational Medicine (2010)
Be open and honest with patients, says Scotland’s chief medical officer
Authors: Bryan Christie
Journal: BMJ (2017)

Attempts are being made in Scotland to empower patients to question their treatment options as the concept of “realistic medicine” is rolled out across the country.

It is based on the idea that overtreatment can lead to harm for patients and waste for the health service when more “realistic” options could produce better results.

Scotland’s chief medical officer, Catherine Calderwood, introduced the concept in her first annual report last year,1 resulting in a reception which she says was “universally positive,” producing …
Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate
Authors: Jenny H Humphreys, Alexander Warner, Ruth Costello, Mark Lunt, Suzanne M M Verstappen, William G Dixon
Journal: Annals of the Rheumatic Diseases (2017)

Background Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care. Methods Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted. Results 11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking &gt;21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93). Conclusions Weekly alcohol consumption of &lt;14 units per week does not appear to be associated with an increased risk of transaminitis.
Polycythemia Vera as a Predisposing Factor for Aortic Stenosis: Prevalence and Correlation with Blood Cells Count and Mutational Status
Authors: Ri ta Barone, Clementina Caracciolo, Rosario di Maggio, Giovanni Fazio, Luciana d’Angelo, Maria Montana, Salvatore Novo, Lucio lo Coco, Domenica Caramazza, Vincenzo Abbadessa, Sergio Siragusa
Journal: Blood (2008)
Varying Importance of Prognostic Factors in Subgroups of Myelodysplastic Syndromes Defined by Blast Count, Cytogenetic Risk Group, or WHO Classification.
Authors: Andrea Kuendgen, Corinna Strupp, Kathrin Nachtkamp, Barbara Hildebrandt, Rainer Haas, Norbert Gattermann, Ulrich Germing
Journal: Blood (2009)
Response to a Large Polio Outbreak in a Setting of Conflict — Middle East, 2013–2015
Authors: Chukwuma Mbaeyi, Michael J. Ryan, Philip Smith, Abdirahman Mahamud, Noha Farag, Salah Haithami, Magdi Sharaf, Jaume C. Jorba, Derek Ehrhardt
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

As the world advances toward the eradication of polio, outbreaks of wild poliovirus (WPV) in polio-free regions pose a substantial risk to the timeline for global eradication. Countries and regions experiencing active conflict, chronic insecurity, and large-scale displacement of persons are particularly vulnerable to outbreaks because of the disruption of health care and immunization services (1). A polio outbreak occurred in the Middle East, beginning in Syria in 2013 with subsequent spread to Iraq (2). The outbreak occurred 2 years after the onset of the Syrian civil war, resulted in 38 cases, and was the first time WPV was detected in Syria in approximately a decade (3,4). The national governments of eight countries designated the outbreak a public health emergency and collaborated with partners in the Global Polio Eradication Initiative (GPEI) to develop a multiphase outbreak response plan focused on improving the quality of acute flaccid paralysis (AFP) surveillance* and administering polio vaccines to >27 million children during multiple rounds of supplementary immunization activities (SIAs).† Successful implementation of the response plan led to containment and interruption of the outbreak within 6 months of its identification. The concerted approach adopted in response to this outbreak could serve as a model for responding to polio outbreaks in settings of conflict and political instability.
Validation study of the Japanese version of M.D. Anderson Symptom Inventory Brain Tumor Module.
Authors: Shota Tanaka, Iori Sato, Terri S. Armstrong, Charles S. Cleeland, Tito R. Mendoza, Akitake Mukasa, Yoshitaka Narita, Kiyoko Kamibeppu, Nobuhito Saito
Journal: Journal of Clinical Oncology (2015)

e17658 Background: It has been recognized that patient reported outcomes measures be incorporated into the assessment of clinical benefit of novel therapies for brain tumor patients, with growing evidence for the value of symptom burden reporting in the evaluation of both disease and treatment related symptoms. M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) is a widely-used modular instrument for measuring symptom burden in brain tumor patients in several large randomized trials. The purpose of this study is to develop and validate the Japanese version of MDASI-BT (MDASI-BT-J). Methods: Following linguistic validation of MDASI-BT-J using the standard back-translation and cognitive debriefing, it was applied to patients with brain tumors undergoing oncologic treatments in The University of Tokyo Hospital from 2014 to 2015. Clinical data were obtained from treating physicians. Feasibility, reliability, and validity of MDASI-BT-J were assessed. Results: Cognitive debriefing confirmed that most patients correctly understood the questionnaires and completed them with ease. The interim analysis evaluated 54 patients (median age 47.5 years, 27 men, median Karnofsky Performance Status (KPS) score 90). Mean symptom score (MSC) and mean interference score (MIS) were 1.7±1.5 and 2.3±2.6, respectively. The median amount of time required to complete the form was 3.5 minutes (range, 1-20), and the percentage of missing value was 0.5 %. Internal consistency using Cronbach’s coefficient alpha was 0.91-0.92. Test-retest reliability was assessed in 30 patients with high intra-class correlation coefficient (0.68-0.83). Known group validity was confirmed given that both MSC and MIC were sensitive to KPS score (P= 0.01 and 0.004, respectively). Concurrent validity using EuroQol 5-Dimension was satisfactory with acceptable correlation coefficient (0.62-0.64). Conclusions: The interim analysis strongly indicates that the newly diagnosed MDASI-BT-J is a reliable instrument for the assessment of clinical benefit in brain tumor patients in Japan, with final analysis presented at the meeting.
Acute myocardial infarction hospital admissions and deaths in England: a national follow-back and follow-forward record-linkage study
Authors: Perviz Asaria, Paul Elliott, Margaret Douglass, Ziad Obermeyer, Michael Soljak, Azeem Majeed, Majid Ezzati
Journal: The Lancet Public Health (2017)

Little information is available on how primary and comorbid acute myocardial infarction contribute to the mortality burden of acute myocardial infarction, the share of these deaths that occur during or after a hospital admission, and the reasons for hospital admission of those who died from acute myocardial infarction. Our aim was to fill in these gaps in the knowledge about deaths and hospital admissions due to acute myocardial infarction.
Molecular Predictors of Outcome in Patients with MDS and AML Following MDS after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Michael Heuser, Christian Koenecke, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Victoria Panagiota, Sabrina Klesse, Michael Stadler, Juergen Krauter, Elke Dammann, Martin Wichmann, Rabia Shahswar, Sabin Bhuju, Robert Geffers, Brigitte Schlegelberger, Gudrun Göhring, Moritz Kleine, Wiebke Brauns, Uwe Platzbecker, Christian Thiede, Thomas Schroeder, Guido Kobbe, Arnold Ganser, Nicolaus Kroeger, Felicitas Thol
Journal: Blood (2015)
Genome-wide association study (GWAS) of efficacy and safety endpoints in pazopanib- or sunitinib-treated patients with renal cell carcinoma (RCC).
Authors: Toby Johnson, Chun-fang Xu, Toni K. Choueiri, Robert A. Figlin, Cora N. Sternberg, Karen S King, Zhengyu Xue, Sandy Stinnett, Keith C. Deen, Christopher Carpenter, Colin F. Spraggs, Arundathy N. Bartlett-Pandite, Robert J. Motzer
Journal: Journal of Clinical Oncology (2014)

4503 Background: Pazopanib and sunitinib are angiogenesis inhibitors approved for treatment of advanced RCC, but there is substantial heterogeneity in response to either treatment. We hypothesized that patient's germline genetic variation may affect treatment efficacy or safety endpoints. Methods: N=1099 patients, from the COMPARZ study (NCT00720941, NCT01147822, N=374 pazopanib, N=355 sunitinib) and three other phase II/III pazopanib studies (NCT00244764, NCT00334282, NCT00387764, N=370), provided consent for pharmacogenetic research. GWAS analyses used normal, ordinal, and Cox regression models to test 30M genetic variants (genotyped or imputed) for association with progression free survival (PFS), overall survival (OS), and best response (BR) in pazopanib or sunitinib treated patients, and with safety endpoints in pazopanib treated patients (bilirubin elevation, transaminase elevation, blood pressure change, hand foot syndrome [HFS], diarrhoea, fatigue, cardiotoxicity, hypothyroidism, proteinuria). Results: At the GWAS significance level for common variants (P≤5x10-8), combined analysis of PFS, OS and BR identified an association with a common variant intronic in LOXL2 and ENTPD4 (P=1.7x10-8). No common variants reached P≤5x10-8 for individual efficacy endpoints, but hypothesis-generating efficacy associations approaching GWAS significance (P≤5x10-7) were observed in and near biologically plausible genes for RCC (e.g. IL2RA, LRRC2). For safety endpoints, common variants near UGT1A1 were associated with bilirubin elevation in pazopanib treated patients (P=2.9x10-17), consistent with our previous candidate gene analysis results. A common variant intergenic between ANAPC4 and SLC34A2 was associated with HFS (P=4.6x10-8). Conclusions: To our knowledge, this is the largest GWAS for response and toxicity to anti-angiogenesis therapies in RCC reported to date. We identified genetic markers associated with combined efficacy endpoints as well as safety endpoints. If replicated in independent studies, these associations may provide insight into biological mechanisms underlying differential outcome to treatment.
Second primary malignancies (SPM) in newly diagnosed myeloma (MM) patients treated with lenalidomide (Len): Meta-analysis of 6,383 individual patient data (IPD).
Authors: Antonio Palumbo, Sara Bringhen, Vincent Rajkumar, Giulia Lupparelli, Saad Zafar Usmani, Anders Waage, Alessandra Larocca, Bronno van der Holt, Pellegrino Musto, Andrea Evangelista, Sonja Zweegman, Meletios A. Dimopoulos, Roman Hajek, Michele Cavo, Sagar Lonial, Giovannino Ciccone, Mario Boccadoro, Bart Barlogie, Pieter Sonneveld, Philip L. McCarthy
Journal: Journal of Clinical Oncology (2013)

8517 Background: An increased risk of SPM in MM pts treated with len has been reported. We performed an IPD metanalysis to estimate the incidence of SPM according to len exposure. Methods: Randomized studies of MM, from PubMed and ASCO/IMW/ASH (after 2000), that met the following criteria, were included: randomization to treatment with len (len-trials); randomization to treatment including new drug but not len (no-len-trials); available SPM data. Primary aim was to estimate cumulative incidence of SPMs by len exposure, corrected for death (competing event). Results: Data from 6,383 pts (3,218 from 8 len-trials, 3,165 from 10 no-len-trials) were analyzed. Median age was 69 years. During follow-up (median=30 mos) 420 (6.6%) SPMs were reported: 188 (2.9%) hematologic and 232 (3.6%) solid cancers. Solid tumors occurred with similar incidence in all groups. Incidence of hematologic SPM was significantly higher in patients receiving len (3.2 vs 1.1, p=0.04), but risk is limited to patients treated with melphalan+len (4.1, 95%CI: 2.4-5.8) with no excess in other combinations (len without melphalan: 1.2, 0.0-2.6; melphalan without len: 1.1, 0.0-2.7) (p=0.003). The cumulative incidence of death for any cause was much higher than the risk of SPM. Conclusions: The risk of hematologic SPMs was higher in pts receiving melphalan+len. The benefit/risk profile of len treatment remains positive. Cumulative incidence (%) of SPMs and death (95%CI). [Table: see text]
Secondary Cytogenetic Abnormalities and Outcome in Children with TEL-AML1-Positive Acute Lymphoblastic Leukemia.
Authors: Oussama A. Abla, Johann Hitzler, Charles Ye, Mohamed Abdelhaleem, Ronald Grant, Gloria Nie, Shanthini Kangesan, Ikuko Teshima, Mary Shago
Journal: Blood (2005)
Analysis of clinical and immunologic phenotype in a large cohort of children and adults with cartilage-hair hypoplasia
Authors: Svetlana Kostjukovits, Paula Klemetti, Helena Valta, Timi Martelius, Luigi D. Notarangelo, Mikko Seppänen, Mervi Taskinen, Outi Mäkitie
Journal: Journal of Allergy and Clinical Immunology (2017)
FDG PET/CT in Pediatric Neurolymphomatosis
Authors: Carole de Vaugelade, Henri de Clermont-Gallerande, Marie Meyer, Aude My Duyen Tiphaine, Alice Benjamin, Stephane Ducassou, Jean-François Chateil, Philippe Fernandez
Journal: Clinical Nuclear Medicine (2017)

An 8-year-old girl presented with back and leg pain and left arm and leg paresis. Lumbar puncture was suggestive of lymphocytic meningitis without identified organism. A second lumbar puncture demonstrated a large number of lymphoid B cells, with positive immunohistochemical staining for CD20 and CD25, proving the diagnosis of neurolymphomatosis. Brain and spine MRI demonstrated involvement of cervical and lumbosacral nerve roots. FDG PET/CT showed multiple bone metastases in addition to nerve involvement. Postchemotherapy FDG PET/CT demonstrated complete metabolic response.
Clinical impact of dose intensity of initial tyrosine kinase inhibitor (TKI) therapy in accelerated-phase CML (CML-AP).
Authors: Maro Ohanian, Hagop Kantarjian, Alfonso Quintas-Cardama, Susan Mary O'Brien, Srdan Verstovsek, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Elizabeth M Burton, Long Trinh, Alessandra Ferrajoli, Elias Jabbour, Tapan M. Kadia, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6587 Background: For patients (pts) presenting with CML-AP, TKIs are recommended. Although generally well tolerated, dose reductions and/or interruptions are often required. The impact of TKI dose intensity (DI) on CML-AP outcome has not been described. Aim: To determine impact of TKI dose interruptions and/or reductions on outcome in de novo CML-AP. Methods: Overall, 58 CML-AP pts (median age 46 yrs) were treated on consecutive or parallel clinical trials with TKIs as initial therapy: imatinib (n=36), dasatinib (n=5), or nilotinib (n=17). CML-AP features included: blasts ≥15% (n=8), basophils ≥20%, (n=22), platelets &lt;100x10 9 /L (n=3), cytogenetic clonal evolution (n=22), or &gt;1 feature (n=3). We examined the impact of dose reductions, treatment interruptions, and DI (ratio of the dose received vs. the intended dose for the entire treatment duration) on event-free (EFS), transformation-free (TFS), and overall survival (OS). Results: Among 58 pts, 37 required treatment interruptions and/or dose reductions (29 required dose reductions). 12 pts required dose reductions and/or interruptions due to hematologic toxicity and 23 for non-hematologic toxicities. Pts were divided into 3 DI tiers: 100% (n= 21), 90-99%, (n=10), and &lt;90% (n=27). Outcomes were analyzed based on DI tiers and presence or absence of dose reductions as shown in the table. Pts with dose reductions and/or interruptions for hematologic toxicities vs. non-hematologic toxicities had a 24-mo EFS rate of 87% vs. 100% (p=0.05). 24-mo EFS by dose reductions and/or interruptions within 6 mo or later were 100% and 91%, respectively (p =0.7). Conclusions: DI has no significant impact on de novo CML-AP outcome. However, dose interruptions and/or reductions for hematologic toxicities are associated with worse 24-mo EFS, suggesting myelosuppression may in some patients be more a feature of the disease than toxicity from therapy. [Table: see text]
Prognosis of breast cancer as a result of late recurrence in hormone receptor-positive tumor.
Authors: Hee Jeong Kim, Sae Byul Lee, Beom Seok Ko, Jong Han Yu, jong Won Lee, Byung Ho Son, Sei-Hyun Ahn
Journal: Journal of Clinical Oncology (2015)

e11587 Background: To evaluate the trend of prognosis and treatment response of very young breast cancer patients (age ≤ 35 years) Methods: We analyzed data from 9633 breast cancer patients who were part of the Asan Medical Center Breast Cancer Center (AMCBCC) database between 1990 to 2008. The disease free survival (DFS) was evaluated between age group according to the time periods and subtype Results: 778 patients (8.1%) were below than 35 years old and 8855 (91.9%) patients were older than 35 years old. On annual hazard ratio plot, DFS of breast cancer increased over time but DFS of very young breast cancer was not improved from 1990 to 2008. On multivariate analysis adjusted by tumor size, node metastasis and grade, reference as 50 years old patients, HR decreased significantly from below 35 years old in hormone receptor positive, Her2 negative breast cancer. Higher recurrence rate of very young age group was prominent in late recurrence (after 5 years) (HR 2.2, 95%CI 1.5 to 3.1) compared with early recurrence (before 5 years) (HR 1.2 95%CI 0.9 to 1.5) Conclusions: Survival of very young breast cancer patients did not improved over time. In hormone receptor positive breast cancer, late recurrence is the cause of the poor survival in very young breast cancer patients
FBXO11, a Regulator of BCL6 Stability, Is Recurrently Mutated in Burkitt Lymphoma
Authors: Chiara Pighi, Mara Compagno, Qi Wang, Taek-Chin Cheong, Teresa Poggio, Fernanda Langellotto, Paola Francia di Celle, Alberto Zamò, Roberto Chiarle
Journal: Blood (2015)
Expression Profile of CD38 and Related Ectoenzymes in Myeloma Bone Niche: A Rational Basis for the Use of Daratumumab to Inhibit Osteoclast Formation and Activity
Authors: Denise Toscani, Marina Bolzoni, Federica Costa, Valeria Quarona, Valentina Marchica, Cristina Mancini, Eugenia Martella, Sabrina Bonomini, Paola Storti, Antonella Chillemi, Fabrizio Accardi, Benedetta Dalla Palma, Luisa Craviotto, Fabio Malavasi, Franco Aversa, Nicola Giuliani
Journal: Blood (2015)
Premature Mortality Among Patients Recently Discharged From Their First Inpatient Psychiatric Treatment
Authors: Florian Walter, Matthew J. Carr, Pearl L. H. Mok, Aske Astrup, Sussie Antonsen, Carsten B. Pedersen, Jenny Shaw, Roger T. Webb
Journal: JAMA Psychiatry (2017)

Nationwide cohorts provide sufficient statistical power for examining premature, cause-specific mortality in patients recently discharged from inpatient psychiatric services.To investigate premature mortality in a nationwide cohort of patients recently discharged from inpatient psychiatric treatment at ages 15 to 44 years.This single-cohort design included all persons born in Denmark (N = 1 683 385) between January 1, 1967, and December 31, 1996. Exactly 48 599 of these Danish residents were discharged from an inpatient psychiatric unit or ward on or after their 15th birthday, which took place during this study's observation period from January 1, 1982, through December 31, 2011. This group of patients was followed up beginning on their 15th birthday until their death, emigration, or December 31, 2011, whichever came first. Individuals discharged from inpatient psychiatric care at least once before their 15th birthday (n = 5882) were excluded from the study. All data were obtained from the Danish Civil Registration System, Psychiatric Central Research Register, and Register of Causes of Death. Data analysis took place between February 1, 2016, and December 10, 2016.Incidence rates and incidence rate ratios (IRRs) for all-cause mortality and for an array of unnatural and natural causes of death among patients recently discharged from an inpatient psychiatric unit vs persons not admitted to a psychiatric facility. Primary analysis considered risk within the year of first discharge.Of the 48 599 discharged patients who were included in the study, 25 006 (51.4%) were female, 35 660 (73.4%) were aged 15 to 29 years, and 33 995 (70.0%) had a length of stay of 30 days or less. Compared with persons not admitted, patients discharged had an elevated risk for all-cause mortality within 1 year (IRR, 16.2; 95% CI, 14.5-18.0). The relative risk for unnatural death (IRR, 25.0; 95% CI, 22.0-28.4) was much higher than for natural death (IRR, 8.6; 95% CI, 7.0-10.7). The highest IRR found was for suicide at 66.9 (95% CI, 56.4-79.4), followed by alcohol-related death at 42.0 (95% CI, 26.6-66.1). Among the psychiatric diagnostic categories assessed, psychoactive substance abuse conferred the highest risk for all-cause mortality (IRR, 24.8; 95% CI, 21.0-29.4). Across the array of cause-specific outcomes examined, risk of premature death during the first year after discharge was markedly higher than the risk of death beyond the first year of discharge.Clinicians may help protect patients after discharge by serving as a liaison between primary and secondary health services to ensure they are receiving holistic care. Early intervention programs for drug and alcohol misuse could substantially decrease the greatly elevated mortality risk among these patients.