tbuckley/cabot-search huggingface dataset:
Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers
Authors: Karoline B Kuchenbaecker, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Penny Soucy, Joe Dennis, Susan M Domchek, Mark Robson, Amanda B Spurdle, Susan J Ramus, Nasim Mavaddat, Mary Beth Terry, Susan L Neuhausen, Rita Katharina Schmutzler, Jacques Simard, Paul D P Pharoah, Kenneth Offit, Fergus J Couch, Georgia Chenevix-Trench, Douglas F Easton, Antonis C Antoniou
Journal: JNCI Journal of the National Cancer Institute (2016)

Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]–positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10−53). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10−20). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.
Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation
Authors: Haiyan Tan, Kai Yang, Yuxin Li, Timothy I. Shaw, Yanyan Wang, Daniel Bastardo Blanco, Xusheng Wang, Ji-Hoon Cho, Hong Wang, Sherri Rankin, Cliff Guy, Junmin Peng, Hongbo Chi
Journal: Immunity (2017)
Impact of Disease Duration upon Symptom Burden Amongst Patients with Myeloproliferative Neoplasms (MPNs)
Authors: Robyn M. Scherber, Holly Geyer, Claire N. Harrison, Heidi E. Kosiorek, Amylou C. Dueck, Jean-Jacques Kiladjian, Stefanie Slot, Zhijian Xiao, Sonja Zweegman, Federico Sackmann, Ana Kerguelen Fuentes, Dolores Hernandez-Maraver, Konstanze Döhner, Deepti Radia, Pablo J. Muxi, Carlos Besses, Francisco Cervantes, Peter L. Johansson, Bjorn Andreasson, Alessandro Rambaldi, Tiziano Barbui, Karin Bonatz, Andreas Reiter, Francoise Boyer, Gabriel Etienne, Jean-Christophe Ianotto, Dana Ranta, Jean Roy, Jean-Yves Cahn, Norman I Maldonado, Giovanni Barosi, Maria Ferrari, Robert Peter Gale, Gunnar Birgegard, Zefeng Xu, Yu Zhang, Xiujuan Sun, Junqing Xu, Peihong Zhang, Peter A. te Boekhorst, Suzan Commandeur, Harry C. Schouten, Heike L Pahl, Martin Griesshammer, Frank Stegelmann, Thomas Lehmann, Alessandro M. Vannucchi, Francesco Passamonti, Jan Samuelsson, Ruben A. Mesa
Journal: Blood (2015)
Abstract B02: Blood-based epigenetic profiling of circulating cell free nucleosomes in 2000 FIT positive individuals: A novel approach to colorectal cancer detection
Authors: Marielle Herzog, Mark Eccleston, Dorian Pamart, Brieuc Cuvelier, Ib Jarle Christensen, Hans Jørgen Nielson, Jake Micallef, Jason Terrell
Journal: Cancer Research (2017)

Abstract Genome wide epigenetic signals are altered in cancer cells. In addition, circulating nucleosome bound DNA fragments contain the same mutations as matched cancer tissue samples suggesting a tumor origin for at least some circulating nucleosomes. We have developed ELISA tests for circulating nucleosomes (NuQ®) and show that the profile of epigenetic features, including histone modifications and variants, DNA modifications and adducts between nucleosomes and non-histone proteins can be correlated with clinical disease and overcomes a major limitation of simple nucleosome quantification for diagnostic and prognostic use. Validation of this approach in a retrospective cohort of 4800 patients presenting with symptoms of Colorectal diseases generated a diagnostic NuQ® panel with sensitivity of 81% at a specificity of 80% in an age adjusted linear regression model for the detection of Colorectal cancer (CRC). In a subsequent pilot prospective study of 58 subjects, a sensitivity of 91% at 90% specificity was achieved for the detection of CRC. We now present preliminary Nucleosomics® data from the first 2000 individuals of a 14 000 asymptomatic, average risk cohort as part of a prospective clinical comparison with a national Fecal Immunological Screening (FIT) program in Denmark. Successful validation of this approach would provide an affordable, accessible and easily implemented blood based testing alternative to address relatively low compliance of fecal testing. Note: This abstract was not presented at the conference. Citation Format: Marielle Herzog, Mark Eccleston, Dorian Pamart, Brieuc Cuvelier, Ib Jarle Christensen, Hans Jørgen Nielson, Jake Micallef, Jason Terrell. Blood-based epigenetic profiling of circulating cell free nucleosomes in 2000 FIT positive individuals: A novel approach to colorectal cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B02.
The Risk of Expanding the Uninsured Population by Repealing the Affordable Care Act
Authors: Adam E. M. Eltorai, Mahmoud I. Eltorai
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Antithrombotic Activity of Kininogen Is Mediated by Inhibitory Effects of Domain 3 on Thrombin-Induced Platelet Activation, In Vivo.
Authors: Sarmina Hassan, Mohammad M. Khan, Irma Isordia-Salas, Irma Sainz, Sakeen W. Kashem, Bo Liu, R. Balfour Sartor, Robert W. Colman
Journal: Blood (2004)
Annals Story Slam - The Social and Family History of a Physician-in-Training
Authors: Anna Morgan
Journal: Annals of Internal Medicine (2017)

Web Exclusives7 March 2017Annals On Being a Doctor Story Slam - The Social and Family History of a Physician-in-TrainingFREEAnna Morgan, MDAnna Morgan, MDFrom University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0025 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - The Social and Family History of a Physician-in-Training "The Social and Family History of a Physician-in-Training," by Dr. Anna Morgan (Duration 6:05)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania, Philadelphia, Pennsylvania.Current Author Address: Anna Morgan, MD; e-mail, [email protected]med.upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 March 2017Volume 166, Issue 5Page: SS1 ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Where Is the Geriatrician?—Reply
Authors: Julie Bynum, Jeffrey Munson, Anna N. A. Tosteson
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The new “Hesitation Blues”: initiating <i>Mycobacterium avium</i> complex lung disease therapy
Authors: David E. Griffith, Julie V. Philley
Journal: European Respiratory Journal (2017)

The "Hesitation Blues" is a traditional blues/folk tune that was first recorded a century ago. Since that time, more than 40 artists with diverse musical pedigrees have recorded the song, ranging from Lead Belly to Doc and Merle Watson to Hot Tuna. An interesting aspect of the various recordings is that while the narrative of the song consistently expresses carnal frustration, the actual lyrics just as consistently vary from one version to the next. It is, therefore, a fitting and appropriate platform to propose further lyric modification that shifts the emphasis to the frustrating hesitation experienced by physicians who must decide about the initiation of Mycobacterium avium complex (MAC) lung disease therapy. Clinical assessment is the key element for deciding which patient with Mycobacterium avium complex needs therapy <http://ow.ly/90mo3091Bkh>
Polatuzumab Vedotin Combined with Obinutuzumab for Patients with Relapsed or Refractory Non-Hodgkin Lymphoma: Preliminary Safety and Clinical Activity of a Phase Ib/II Study
Authors: Tycel Phillips, Mark Brunvand, Andy Chen, Oliver Press, James Essell, Annalisa Chiappella, Catherine Diefenbach, Surai Jones, Jamie Hirata, Ian W. Flinn
Journal: Blood (2016)
Abstract P4-10-02: Transmembrane protein 33 (TMEM33) induces apoptosis via UPR signaling and autophagy in breast cancer cells
Authors: R Clarke, R Hu, X Zhang, L Hilakivi-Clarke, U Kasid
Journal: Cancer Research (2017)

Abstract Breast cancer is the most common cancer diagnosed in women. Endoplasmic reticulum stress (EnR stress) and the related unfolded protein response (UPR) are activated in breast cancer cells and can promote cell survival and endocrine resistance. TMEM33 is a novel transmembrane protein that resides in the endoplasmic reticulum (EnR) and has been shown to activate the PERK and IRE1α branches of the UPR. However, the underlying mechanism of action of this EnR resident protein TMEM33 and the cellular functions that it regulates remain largely unknown. In this study, we show that overexpression of TMEM33 induces robust cell death in breast cancer cells. TMEM33 overexpression strongly activates UPR associated pro-death JNK-p53 signaling. We also observed a significant inhibition of the downstream survivin, which blocks cell death activation by binding to caspases and inhibiting their activation. We further show that the blockage of JNK activation with either an inhibitor or overexpression of survivin, protects cells against TMEM33 induced apoptosis. In addition, we show that TMEM33 overexpression induces autophagy in breast cancer cells. Inhibition of autophagy with using either the inhibitor chloroquine or knockdown of the Atg5 gene, further sensitizes breast cancer cells to the effects of TMEM33 overexpression. Cell death induced by TMEM33 is also decreased by overexpression of the autophagy gene Beclin 1. The findings in this study demonstrate that the novel EnR resident protein TMEM33 induces cell death by activating IRE1α-JNK-p53-survivin signaling in breast cancer cells. Concurrently, autophagy is also activated by TMEM33, and functions as a pro-survival mechanism. Cell fate reflects the balance between the pro-death and pro-survival activities as regulated by TMEM33. Citation Format: Clarke R, Hu R, Zhang X, Hilakivi-Clarke L, Kasid U. Transmembrane protein 33 (TMEM33) induces apoptosis via UPR signaling and autophagy in breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-10-02.
Presence of JAK2 Mutations in MDS/MPD-u WHO Classified Patients and Not Other Forms of MDS Suggests Their Derivation from Classical Myeloproliferative Syndrome.
Authors: Hadrian Szpurka, Ramon Tiu, Eric Hsi, Alan E. Lichtin, Mikkael A. Sekeres, Karl S. Theil, Jaroslaw P. Maciejewski
Journal: Blood (2005)
Catheter retention as a consequence rather than a cause of unfavorable outcome in candidemia
Authors: Lauro Damonti, Véronique Erard, Jorge Garbino, Jacques Schrenzel, Stefan Zimmerli, Konrad Mühlethaler, Alexander Imhof, Reinhard Zbinden, Jan Fehr, Katia Boggian, Thomas Bruderer, Ursula Flückiger, Reno Frei, Christina Orasch, Anna Conen, Nina Khanna, Thomas Bregenzer, Jacques Bille, Frédéric Lamoth, Oscar Marchetti, Pierre-Yves Bochud
Journal: Intensive Care Medicine (2017)
Antineutrophil cytoplasmic antibodies: reporting and diagnostic strategies
Authors: Jan Damoiseaux, Elena Csernok, Niels Rasmussen, Jan-Willem Cohen Tervaert, Xavier Bossuyt
Journal: Annals of the Rheumatic Diseases (2017)

It was with great interest that we read the correspondence of Mahler and Fritzler1 on our recent European Vasculitis Study Group (EUVAS) study describing the performance of immunoassays for antineutrophil cytoplasmic antibodies (ANCA) in patients with ANCA-associated vasculitides (AAV).2 In their letter, Mahler and Fritzler raise some interesting points, mainly related to (i) test result interpretation and (ii) diagnostic strategies. Besides, they pointed out that in the EUVAS study only two indirect immunofluorescence (IIF) assays were included, a commercial assay from Inova Diagnostics and a ‘home-made’ assay. They suggested to perform studies with more than two IIF ANCA tests and especially to include assays that are most commonly used in diagnostic laboratories. In a concomitant publication, we presented data on two additional commercial IIF assays, one from Euroimmun and one from Medipan.3 Accordingly, we postulate that we included the most commonly used IIF assays. For example, IIF ANCA assays from Inova and Euroimmun are used by, respectively, 50% and 23% of the participants of the UK National External Quality Assessment Service (NEQAS) ANCA scheme (report September 2016). Our studies consistently showed that test characteristics of IIF were highly variable between assays. We envisaged that this variability was dependent on the substrates used and methods applied for ANCA IIF testing, that is, the use of only ethanol-fixed neutrophils versus the combination of ethanol-fixed and formalin-fixed neutrophils and HEp2 cells.3 Moreover, we also found that the overall performance of high-quality immunoassays was at least as good as the performance of IIF methods, even when applied on modern automated systems. These observations lead us to conclude that the current international guidelines on ANCA …
Erythrocyte Rigidity Affects Blood Clot Contraction and Formation of Polyhedrocytes
Authors: Valerie Tutwiler, Rustem I. Litvinov, Chandrasekaran Nagaswami, J. Eric Russell, Don L. Siegel, Carlos Hipolito Villa, Daniel Pan, Vladimir R Muzykantov, John W. Weisel
Journal: Blood (2016)
TP53-Induced Glycolysis and Apoptosis Regulator Protects from Spontaneous Apoptosis and Predicts Poor Prognosis in Chronic Lymphocytic Leukemia
Authors: Ming Hong, Yi Xia, Yu Zhu, Huihui Zhao, Yue Xie, Lei Fan, Li Wang, Kourong Miao, Wei Wu, Huayuan Zhu, Yaoyu Chen, Wei Xu, Sixuan Qian, Jianyong Li
Journal: Blood (2016)
The FRAX score as a tool for estimating fracture risk in patients with advanced prostate cancer on androgen-deprivation therapy compared to the conventional T-score.
Authors: Marc Nicolas Bienz, Herbert James, Ilija Aleksic, Christopher Michael Pieczonka, Peter Iannotta, David Albala, Neil Mariados, Vladimir Mouraviev, Fred Saad
Journal: Journal of Clinical Oncology (2014)

e16023 Background: Prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT) are at increased risk of developing bone deficiency and associated morbidities due to hypogonadism-induced secondary osteoporosis. A FRAX algorithm has been elaborated to estimate the ten-year hip fracture risk associated with this under-diagnosed condition. We aim to evaluate the fracture risk of patients who would otherwise been left untreated by the conventional T-score. Methods: Clinical data from 613 PCa patients undergoing ADT was collected at our urology group. Fracture risk was assessed using the country specific (USA) Fracture Risk Assessment Tool (FRAX). Also, a subset of patients (n=94) had received Dual-energy X-ray Absorptiometry (DXA). We compared the proportion of those suitable for treatment according to the threshold of the FRAX fracture risk calculated with the BMD (>3%) and the T-score (<-2.5). Results: According to the FRAX algorithm (without BMD), 61.6% of our cohort require treatment. The FRAX score (with BMD) identified 46.8% of patients who had DXA suitable for treatment, in contrast to 19.1% by the T-score alone. Correlations were calculated between the various methods. Conclusions: Our results demonstrate that many patients unidentified for treatment by the conventional T-score were at significant risk for fracture according to the FRAX algorithm. When calculated without the BMD, the biggest proportion of patients was found at risk and suitable for treatment. Therefore, the FRAX score could be beneficial for better fracture prevention with effective bone-tropic therapy in patients undergoing ADT. Correlation R P-value FRAX with and without BMD 0.44 < 0.005 FRAX with BMD and T-score -0.795 < 0.005 FRAX without BMD and T-score -0.318 < 0.005
Deletion of Puma and p21Waf1 In Mice Deactivates p53-Induced Cell Death and Cell Cycle Arrest, but Protects Mice From Irradiation-Induced Lymphomagenesis by a Mechanism Involving Hemopoietic Stem Cell Quiescence
Authors: Josefina Pinon Hofbauer, Claudia Holler, Ursula Denk, Daniela Asslaber, Gerd Fastner, Verena Labi, Andreas Villunger, Richard Greil, Alexander Egle
Journal: Blood (2010)
Incomplete polyp resection – no simple solution
Authors: Heiko Pohl
Journal: Endoscopy (2017)

It has been estimated that incomplete adenoma resection is responsible for 10 % – 30 % of postcolonoscopy colorectal cancers (CRC) [1]. Several studies have shown that polyp removal is often incomplete, although data on polyps that are larger than diminutive are still limited [2] [3] [4] [5] [6] [7] [8]. A 10 % incomplete resection rate has been reported for neoplastic polyps of 5 – 20 mm [8]. Considering that complete resection is required to assure effective CRC screening and surveillance, three questions deserve attention.
The Histone Deacetylase Inhibitor LAQ824 Maintains Normal Hematopoietic Progenitor cells (HPC) Associated with Induction of Notch Target Genes and Does Not Eliminate Leukemic HPC in Vitro.
Authors: Kerstin Schwarz, Oliver Ottmann, Annette Romanski, Anja Vogel, Jeffrey W. Scott, Hubert Serve, Gesine Bug
Journal: Blood (2008)
Thymic Hyperplasia after Chemotherapy: Combined Experience of Two Centers
Authors: Pamela Dominguez-Perez, Nicole Maxey, Zeinab Mohammadi, Erasto Cortes, Nishaal Antony, Anuradha Gupta, Mark M Landeros, Angel Campos-Gines, Ethan Reiter, Carmen Arango, Javier Gutierrez, Elena Morales, Matilde Gonzalez, Juan Herrada
Journal: Blood (2015)
Serious Acute or Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplantation: A Comparison of Myeloablative and Non-Myeloablative Conditioning Regimens.
Authors: Olga Sala-Torra, Paul J. Martin, Barry Storer, Mohamed Sorror, Rainer F. Storb, Brenda M. Sandmaier, Mary E.D. Flowers
Journal: Blood (2006)