tbuckley/cabot-search huggingface dataset:
Primary fallopian tube lesions in <i>BRCA</i> mutation carriers undergoing risk-reducing surgery.
Authors: F. Dao, G. Han, K. J. Park, G. J. Gardner, N. D. Kauff, R. R. Barakat, R. A. Soslow, D. A. Levine
Journal: Journal of Clinical Oncology (2010)

1512 Background: The fallopian tube (FT) has been identified as a likely site of occult disease in patients (pts) undergoing risk- reducing salpingo-oophorectomy (RRSO) for the prevention of primary ovarian cancer. In recent studies, thorough pathologic examination of the adnexa has identified tubal intraepithelial carcinoma (TIC) in 4%-10% of BRCA-positive pts undergoing RRSO. Our objective was to review the incidence of primary FT lesions in BRCA-positive women undergoing RRSO at a single comprehensive cancer center. Methods: Pts undergoing RRSO between January 2005 and August 2009 were identified from operative records. Clinical and pathologic information were collected from the medical record. In all cases, the FTs were entirely submitted, serially sectioned, and the fimbriated end extensively examined by a GYN specialty pathologist. IHC was used only to confirm clinical diagnoses in equivocal cases. Results: We identified 158 pts with BRCA mutations documented in the medical record. Eighty-three (52%) pts were Jewish, 42 (27%) were Catholic, 33 (21%) were of other religions. The median age at time of surgery was 48 years (range, 33-79 years). Fifty-nine pts had a BRCA1 mutation, 56 had a BRCA2 mutation, and 43 had a documented germline BRCA mutation, not otherwise specified. All mutations were known to be deleterious. The most frequent mutations found were BRCA1 185delAG (23, 15%), BRCA2 6174delT (18, 11%), and BRCA1 5382insC (8, 5%). Two cases of TIC (1.3%) were identified. Three additional pts (2%) were found to have epithelial dysplasia/p53 signature lesions of the FT. Immunohistochemical stains confirmed that these three lesions had p53 overexpression without increased proliferation or nuclear atypia. No cases of invasive ovarian or tubal carcinoma were identified, and all proximal FTs were normal. Conclusions: The incidence of TIC in this study is lower than in previously published reports while considering that all pts had deleterious BRCA mutations and comprehensive processing of the FTs. This may be due to a different mutational spectrum, tissue processing protocols, or sample ascertainment biases. Refining the estimates of TIC and occult malignancies has useful implications for cancer prevention. No significant financial relationships to disclose.
Targeting Survivin In Recalcitrant Acute Lymphoblastic Leukemia
Authors: Eugene Park, Enzi Jiang, Yao-Te Hsieh, Lars Klemm, Cihangir Duy, Edward M. Conway, Louis M. Pelus, John Crispino, Mignon L. Loh, Eun-Suk Kang, Hong-Hoe Koo, Allen Yang, Nora Heisterkamp, Michael Kahn, Markus Muschen, Yong-Mi Kim
Journal: Blood (2010)
Social media use among young rheumatologists and basic scientists: results of an international survey by the Emerging EULAR Network (EMEUNET)
Authors: Elena Nikiphorou, Paul Studenic, Christian Gytz Ammitzbøll, Mary Canavan, Meghna Jani, Caroline Ospelt, Francis Berenbaum
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To explore perceptions, barriers and patterns of social media (SM) use among rheumatology fellows and basic scientists. Methods An online survey was disseminated via Twitter, Facebook and by email to members of the Emerging European League Against Rheumatism Network. Questions focused on general demographics, frequency and types of SM use, reasons and barriers to SM use. Results Of 233 respondents (47 countries), 72% were aged 30–39 years, 66% female. 83% were active users of at least one SM platform and 71% were using SM professionally. The majority used SM for communicating with friends/colleagues (79%), news updates (76%), entertainment (69%), clinical (50%) and research (48%) updates. Facebook was the dominant platform used (91%). SM was reported to be used for information (81%); for expanding professional networks (76%); new resources (59%); learning new skills (47%) and establishing a professional online presence (46%). 30% of non-SM users justified not using SM due to lack of knowledge. Conclusions There was a substantial use of SM by rheumatologists and basic scientists for social and professional reasons. The survey highlights a need for providing learning resources and increasing awareness of the use of SM. This could enhance communication, participation and collaborative work, enabling its more widespread use in a professional manner.
GW26-e5447 Evaluation of thienopyridine-resistance in Indian patients by measuring platelet aggregation in post-PCI patients receiving antiplatelet medication: Outcomes with ‘AggreGuide A-100’ platelet aggregometer
Authors: Rajasekhar Durgaprasad, Vanajakshamma Velam, Madhavi Rodda, Boochi Babu Mannuva, Vidyasagar Akula, Latheef Kasala
Journal: Journal of the American College of Cardiology (2015)
Added value of combined endobronchial and oesophageal endosonography for mediastinal nodal staging in lung cancer: a systematic review and meta-analysis
Authors: Daniël A Korevaar, Laurence M Crombag, Jérémie F Cohen, René Spijker, Patrick M Bossuyt, Jouke T Annema
Journal: The Lancet Respiratory Medicine (2016)
Cytotoxic Molecule (CM)-Positive Classical Hodgkin Lymphoma: a Clinicopathologic Study in Comparison with Nodal Peripheral T-Cell Lymphoma of Not Otherwise Specified Type Possessing CM Expression.
Authors: Naoko Asano, Jun-Ichi Tamaru, Fumihiro Ishida, Tadashi Yoshino, Yoshitoyo Kagami, Yasuo Morishima, Masao Seto, Tomohiro Kinoshita, Shigeo Nakamura
Journal: Blood (2009)
A Prospective Study of Treatment Outcomes in 179 Patients with Advanced Cardiac Stage STAGE IIIb Amyloidosis
Authors: Belen Sevillano, Ashutosh Wechalekar, Darren Foard, Carol Whelan, Marianna Fontana, Cristina Quarta, Shameem Mahmood, Helen Lachmann, Julian D Gillmore, Philip N Hawkins
Journal: Blood (2015)
No Impact of Postremission Consolidation Chemotherapy Before Allogeneic Transplant in Patients with First Remission Acute Myeloid Leukemia with Intermediate or High Risk Cytogenetics.
Authors: Lisa O. Sproat, Brian Bolwell, Lisa Rybicki, Matt Kalaycio, Robert Dean, Ronald Sobecks, Brad Pohlman, Steve Andresen, Shawnda Sungren, Josephine Chan, John Sweetenham, Ed Copelan
Journal: Blood (2008)
Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion
Authors: Yu Hu, Ji Hyung Kim, Kangmin He, Qi Wan, Jessica Kim, Melanie Flach, Tom Kirchhausen, Andrea Vortkamp, Florian Winau
Journal: The Journal of Experimental Medicine (2016)

In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes. TMEM16F is located in late endosomes, where it facilitates the generation of multivesicular bodies for TCR degradation and signal termination. Consequently, TMEM16F deficiency results in sustained signaling and augmented T cell activation. Our results demonstrate that scramblase restricts TCR responses to avoid overactivation, ensuring a well-balanced immune response in chronic infectious disease.
Prospective Multicenter Study for Patients with Therapy - Related Acute Myeloid Leukemia (AML) Using Intensive Induction and Postremission Therapy.
Authors: Bernhard Josef Wormann, Claudia Schoch, Albrecht Reichle, Peter Staib, Wolf-Dieter Ludwig, Maria Cristina Sauerland, Achim Heinecke, Wolfgang E. Berdel, Wolfgang Hiddemann, Thomas Buchner
Journal: Blood (2006)
Comment on Fischer et al. Text Message Support for Weight Loss in Patients With Prediabetes: A Randomized Clinical Trial. Diabetes Care 2016;39:1364–1370
Authors: Mohsen Afarideh, Alireza Ghajar, Sina Noshad, Alireza Esteghamati
Journal: Diabetes Care (2016)

We read with great interest the article by Fischer et al. (1) that was recently published in Diabetes Care . Although we congratulate the authors for their encouraging findings on the impressive role of text messaging support for weight loss management in prediabetes, their results raise several important concerns.

It is very surprising that weight loss was observed only among Spanish speakers but not in the English-speaking group (1). Do the authors feel confident about the internal validity of their findings (i.e., non–quasi-experiment design), considering the potential diversities in educational status, income, type of cell phones (touch tone, large-screen displays), socioeconomic background, and type of personality (motivation, incorporation of family and friends into …
Young women who are obese are often unaware of risks to fetus, experts warn
Authors: Joe Freer
Journal: BMJ (2016)

Young women who are overweight or obese are often unaware of being on a health trajectory that can cause biological risks to be passed on to unborn children, experts have warned.

An expert panel hosted by the Parliamentary Office of Science and Technology on Wednesday 19 October highlighted the increase in morbidity related to excess weight among mothers and their children over the past 10 years and the overwhelming evidence of health risks being passed from mother to child.

The panel—Lucilla Poston, head of the women’s health division at King’s College London, Mark Hanson, director of the …
A randomized phase II study of EMD 121974 in patients (pts) with metastatic melanoma (MM)
Authors: K. B. Kim, A. H. Diwan, N. E. Papadopoulos, A. Y. Bedikian, L. H. Camacho, P. Hwu, M. M. Johnson, A. D. Colevas, V. G. Prieto
Journal: Journal of Clinical Oncology (2007)

8548 Background: EMD 121974 is a selective antagonist of avβ3 integrin, which promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells expressing avβ3 integrin. We conducted a randomized phase II trial of cilengitide in pts with MM to evaluate the clinical efficacy at 2 different doses. Methods: Pts with stage IV or unresectable stage III non-choroidal melanoma who had no more than 1 prior systemic therapy were enrolled. Pts at least 18 years of age and with ECOG performance status of 0 to 2 were eligible. All pts underwent baseline tumor biopsy and were randomly assigned to either 500 mg or 2,000 mg intravenous (IV) EMD 121974 twice weekly, using the following stratification factors: 1) prior systemic treatment; 2) visceral metastases; 3) serum lactate dehydrogenase level; 4) tumor avβ3 overexpression, where overexpression is defined as &gt; 25% of melanoma cells staining positive. The primary objective of this study was to determine the progression-free survival rate at 8 weeks. Results: Twenty-nine pts were enrolled, and 26 pts (14 at 500 mg; 12 at 2,000 mg dose) were treated. Patient characteristics for 500 mg and 2,000 mg arm, respectively, are as follows: median age, 57 and 61; percentage (% age) of male, 50% and 50%; % age of ECOG performance status of 0, 79% and 58%; % age of stage IV, 79% and 75%; % age of tumor avβ3 overexpression, 21% and 25%. Three of 26 pts were progression-free at 8 weeks (2 at 500 mg; 1 at 2,000 mg dose). One pt at 2,000 mg had a prolonged partial response after initial 28% enlargement of target lesions. There were no grade 3 or 4 adverse events (AEs) except one pt with grade 3 lymphopenia at 2,000 mg. Although both doses of EMD 121974 were well tolerated, the 2,000 mg was associated with higher incidences of grade 2 fatigue, arthralgia, lymphopenia, peripheral neuropathy, and GI AEs. Optional tumor biopsies were performed on day 8, and the correlative studies to examine the molecular changes in the tumor are currently in progress. Conclusions: IV EMD 121974, 500 or 2,000 mg twice weekly, was well tolerated but had minimal clinical efficacy as a single-agent for MM. Supported by NCI grant N01 CM-17003 and CA16672 No significant financial relationships to disclose.
GW26-e1248 Impact of Preoperative Acute Kidney Injury on In-hospital Outcomes in Patients With Type A Acute Aortic Dissection
Authors: Xiao Wang, Hongmei Ren, Chunyan Hu, Bin Que, Hui Ai, Chunmei Wang, Lizhong Sun, Shaoping Nie
Journal: Journal of the American College of Cardiology (2015)
A drug interaction study between ketoconazole and panobinostat (LBH589), an orally active histone deacetylase inhibitor, in patients with advanced cancer
Authors: M. DeJonge, M. M. Woo, D. Van der Biessen, P. Hamberg, S. Sharma, L. C. Chen, N. Myke, L. Zhao, S. Hirawat, J. Verweij
Journal: Journal of Clinical Oncology (2009)

2501 Background: The effects of ketoconazole (keto), a potent CYP3A inhibitor, on the pharmacokinetics (PK) of panobinostat (PAN) were investigated in an open-label, multicenter, cross-over, single sequence study. Methods: Patients (pts) with advanced solid tumors or NHL received single-agent PAN at 20 mg on Day 1 and single-agent keto at 400 mg daily on Days 5–9. On Day 8, PAN 20 mg was administered 1 hour after keto. All pts had adequate organ function and ECOG performance status &lt;2. Serial plasma samples were collected for PAN PK evaluations on Days 1 and 8 and pre- and post-dose keto samples on Days 5, 8, and 9. Plasma PAN and keto concentrations were measured by LC-MS-MS. PK parameters were estimated by using non-compartmental analysis. Genotyping analysis of CYP3A4*1B, CYP3A5*2, *3, *6 and *7 were performed by using AmpliChip CYP450. Results: Fourteen Caucasian patients (9M, 5F) were enrolled with a median age of 59. Fourteen pts had homozygous wide-type CYP3A4*1A genotype, 11 pts had homozygous CYP3A5*3, and three pts had heterozygous CYP3A5*1/*3 genotype. No residual PAN concentrations were detected in pre-dose samples on Day 8. PAN PK parameters were calculated as either mean (CV%), median [range] or ratio (see Table). Single-dose PAN did not affect keto concentrations. Co-administration of keto and PAN increased PAN C max and AUC by 1.6- and 1.7-fold, respectively, but with no change in T max . There was no apparent difference in PAN PK between pts who carried CYP3A5*1 allele and homozygous CYP3A5*3 carriers. Conclusions: The less than 2-fold increase in PAN AUC upon co-administration suggests that CYP3A contribution to the total clearance of PAN is low. The observed interaction is not considered clinically relevant, as PAN doses are at least 2-fold greater than 20 mg (40 and 60 mg) have been safely administered in pts. CYP3A4 inhibitors should have no major impact on the exposure of PAN and may be co-administered when medically necessary. [Table: see text] [Table: see text]
Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality
Authors: Xiao Yu, Baowei Cai, Mingjun Wang, Peng Tan, Xilai Ding, Jian Wu, Jian Li, Qingtian Li, Pinghua Liu, Changsheng Xing, Helen Y. Wang, Xin-zhuan Su, Rong-Fu Wang
Journal: Immunity (2016)
Association of Persistent Postconcussion Symptoms With Pediatric Quality of Life
Authors: Zuzana Novak, Mary Aglipay, Nick Barrowman, Keith O. Yeates, Miriam H. Beauchamp, Jocelyn Gravel, Stephen B. Freedman, Isabelle Gagnon, Gerard Gioia, Kathy Boutis, Emma Burns, Andrée-Anne Ledoux, Martin H. Osmond, Roger L. Zemek
Journal: JAMA Pediatrics (2016)

Persistent postconcussion symptoms (PPCS) pose long-term challenges and can negatively affect patients' health-related quality of life (HRQoL). To date, no large comprehensive study has addressed the association between PPCS and HRQoL.To determine the association between HRQoL and PPCS at 4 weeks after concussion and assess the degree of impairment of HRQoL in the subsequent 12 weeks.In a prospective, multicenter cohort study (Predicting Persistent Postconcussive Problems in Pediatrics [5P]) from August 14, 2013, to September 30, 2014, children aged 5 to 18 years who presented to the emergency department within 48 hours after head injury and were considered to have an acute concussion were enrolled across 9 pediatric emergency departments within the Pediatric Emergency Research Canada Network. Persistent postconcussion symptoms were defined as 3 or more persistent symptoms on the validated Post-Concussion Symptom Inventory at 4 weeks. Linear mixed effects random coefficients models evaluated the association between PPCS and HRQoL, adjusting for potential confounders including age, sex, prior concussions, migraine, anxiety, learning disability, depression, and sleep disorder.The primary outcome was HRQoL assessed with the validated Pediatric Quality of Life Inventory version 4.0 (PedsQL-4.0) at 4, 8, and 12 weeks after head injury.Of 2006 children enrolled (median age, 11.8 years [interquartile range, 8.9-14.6 years]; 1241 boys and 765 girls), 1667 (83.1%) completed the PedsQL-4.0 at all 3 time points. Of these 1667 children, the 510 with PPCS (30.6%) had lower total PedsQL-4.0 scores (mean, 70.0) than did those without PPCS (mean, 80.3; mean difference, -10.3; 95% CI, -9.4 to -11.2). Patients with PPCS also had significantly lower physical, emotional, social, and school PedsQL-4.0 subscores at 4, 8, and 12 weeks. Patients with PPCS had lower HRQoL than published healthy norms at 4 weeks (mean difference, 13.89; 95% CI, 11.55-16.23), 8 weeks (mean difference, 11.63; 95% CI, 9.34-13.93), and 12 weeks (mean difference, 9.38; 95% CI, 7.01-11.75; P < .001). Patients who recovered from concussion also had lower HRQoL than norms at 4 weeks (mean difference, 3.56; 95% CI, 1.28-5.85) and 8 weeks (mean difference, 2.75; 95% CI, 0.48-5.02; P < .05). School functioning PedsQL-4.0 subscores were significantly lower for all children regardless of PPCS status at all time points.Children with PPCS have lower HRQoL compared with those who have recovered from concussion, yet deficits in HRQoL are pervasive across all domains and may persist for months even in children whose symptoms have resolved. Future interventional research should target the effect of concussion on HRQoL.
SIRT2 Plays Essential Role in Early Hematopoiesis through Deacetylation of LMO2 Protein
Authors: Tatsuya Morishima, Regine Bernhard, Azadeh Zahabi, Benjamin Dannenmann, Masoud Nasri, Bardia Samareh, Lothar Kanz, Karl Welte, Julia Skokowa
Journal: Blood (2015)
Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
Authors: Corina Lesseur, Brenda Diergaarde, Andrew F Olshan, Victor Wünsch-Filho, Andrew R Ness, Geoffrey Liu, Martin Lacko, José Eluf-Neto, Silvia Franceschi, Pagona Lagiou, Gary J Macfarlane, Lorenzo Richiardi, Stefania Boccia, Jerry Polesel, Kristina Kjaerheim, David Zaridze, Mattias Johansson, Ana M Menezes, Maria Paula Curado, Max Robinson, Wolfgang Ahrens, Cristina Canova, Ariana Znaor, Xavier Castellsagué, David I Conway, Ivana Holcátová, Dana Mates, Marta Vilensky, Claire M Healy, Neonila Szeszenia-Dąbrowska, Eleonóra Fabiánová, Jolanta Lissowska, Jennifer R Grandis, Mark C Weissler, Eloiza H Tajara, Fabio D Nunes, Marcos B de Carvalho, Steve Thomas, Rayjean J Hung, Wilbert H M Peters, Rolando Herrero, Gabriella Cadoni, H Bas Bueno-de-Mesquita, Annika Steffen, Antonio Agudo, Oxana Shangina, Xiangjun Xiao, Valérie Gaborieau, Amélie Chabrier, Devasena Anantharaman, Paolo Boffetta, Christopher I Amos, James D McKay, Paul Brennan
Journal: Nature Genetics (2016)
MicroRNA for circulating tumor cells detection in breast cancer: In silico and in vitro analysis
Authors: V. Medina Villaamil, M. Blanco Calvo, S. M. Díaz Prado, S. Antolín Novoa, L. Calvo Martínez, I. Santamarina Caínzos, M. Haz Conde, L. M. Antón Aparicio, M. Valladares-Ayerbes
Journal: Journal of Clinical Oncology (2009)

e22027 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in breast cancer (bc) patients. Deregulation of microRNAs (miRNAs) is frequent in tumors, including breast cancer. It is suggested miRNAs play a role in tumor progression. We hypothesized that miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. Our objective has been to identify miRNAs potentially useful for CTC detection. Methods: Phase I preclinical study was performed by means of computational tools for miRNAs profiling including MIRGATOR, MIRBASE, SMIRNAdb, GeneHUB-GEPIS, MICRORNA.ORG, and MIRNAMAP. In silico data were used to identify and prioritize miRNAs highly expressed in breast cancer, but absent in hematopoietic-derived sources. Selected miRNAs were evaluated by means of qRT-PCR in breast cancer and Hematopoietic cell lines, normal blood, and blood from breast cancer patients. Results: Computational tools identify a set of miRNAs highly expressed in breast cancer sources in relation to hematopoietic samples. Among these were miR-141, miR-200c, miR-196a, miR-203, miR-200a, miR-200b, miR-32, miR-375, miR-31, miR-193a, and miR-205. For instance, relative expression of miR-32 was 10 4 higher in bc cell lines (N= 5) than in normal PB (N = 19) using qRT-PCR. In a preliminary analysis of PB from bc patients (stage IV) higher relative expression levels for selected miRNAs were found comparing with age-matched controls’ blood. Conclusions: Our results suggest that miRNA bioinformatic approach is a useful high-throughput method to select bc-associated miRNAS. The selected miRNAs should be further evaluated for their potential as markers for CTC detection. We next investigate if blood miRNA profile could predict tumor progression and survival. Supported by grants PI06/1541 and PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.
Prospective Analysis of Cytomegalovirus Reactivation and the Immune State of Low-Grade B-Cell Lymphoma Patients Treated with Bendamustine
Authors: Noriko Isono, Yoichi Imai, Chihiro Asano, Michihiko Masuda, Shigeru Hoshino, Keiichi Moriya, Hideto Tamura, Koiti Inokuchi, Shigeki Ito, Yoji Ishida, Toshiko Motoji, Junji Tanaka
Journal: Blood (2014)
Calcium Intake and Cardiovascular Disease Risk
Authors: Mei Chung, Alice M. Tang, Zhuxuan Fu, Ding Ding Wang, Sydne Jennifer Newberry
Journal: Annals of Internal Medicine (2016)

Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake.To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults.MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016.Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes.Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias.Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically significant differences in risk for CVD events or mortality between groups receiving supplements of calcium or calcium plus vitamin D and those receiving placebo. Cohort studies showed no consistent dose-response relationships between total, dietary, or supplemental calcium intake levels and cardiovascular mortality and highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality.CVD disease outcomes were secondary end points in all trials. Dose-response metaregression analysis of cohort studies was limited by potential confounding, ecological bias, and imprecise measures of calcium exposures. Data were scarce regarding very high calcium intake-that is, beyond recommended tolerable upper intake levels.Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults.National Osteoporosis Foundation.