tbuckley/cabot-search huggingface dataset:
Abstract 2096: Variants of uncertain clinical significance in cancer predisposition genes: Development of a family studies program for reclassification
Authors: Aaron J. Stuenkel, Ira Lu, Elizabeth C. Chao
Journal: Cancer Research (2012)

Abstract The identification of genetic variants of uncertain significance is a fairly common, albeit unwelcomed result of gene sequence analyses. The frequency at which these variants are identified will likely continue to increase with the introduction of next-generation sequencing panels and the recent availability of clinical exome sequencing. When applied to testing for cancer predisposition syndromes, accurate variant assessment and classification helps to guide screening, treatment, family planning, and testing of at-risk family members. Multiple resources are available to assess genetic variants: population-based cohort allele frequencies, published literature, in silico prediction tools, gene-specific databases, evolutionary conservation data, and co-segregation studies. Ambry Genetics, a CAP-accredited and CLIA-certified commercial clinical laboratory providing genetic services focused on clinical diagnostics and genomic services, has developed and implemented a complementary family studies program to collect co-segregation data for variants of unknown significance identified through diagnostic testing. The Ambry family studies program is available to all specialties, but is especially active for genes associated with cancer predisposition and intellectual disability. Data collected from the cancer family studies program is combined with published literature, database information, and data compiled with Ambry Variant Analyzer (AVA©), a novel bioinformatics tool, to allow for a comprehensive interpretation of all variants of uncertain clinical significance in cancer predisposition genes. In less than one year, the program has grown to 60 active cancer family studies at the time of submission and a current rate of &amp;gt;5 new applications per week. Variants successfully reclassified due to family studies data include the p.Y327D missense alteration in MEN1 and in-frame deletions in both TP53 and MLH1. Variant reclassification leads to the automatic generation of amended reports for any individual previously identified by our laboratory as a carrier. Immediately distributed to health care professionals, these reports offer the most up-to-date clinical interpretation possible improving medical decision making and clarifying risk of disease. Here we provide an overview of the family studies program and discuss successful variant reclassification via the Ambry model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2096. doi:1538-7445.AM2012-2096
SAT0516 Identification of Subclinical Tophi in Gout Using Dual Energy Computed Tomography
Authors: I.J. Kim, J.Y. Hwang, J. Lee
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The presence of tophi is associated with impairment of health-related quality of life as well as increase in prevalence of comorbidities in patients with gout. <h3>Objectives</h3> The purpose of our study was to evaluate the utility of dual-energy CT (DECT) in detecting subclinical tophi in patients with gouty arthritis. <h3>Methods</h3> Paired plain radiographs and DECT scans of foot joints in 6 patients with gout who had prior history of acute gouty arthritis in joints of foot without clinical tophi were evaluated for the presence of subclinical tophi. Foot joints included 22 metatarsophalangeal (MTP), interphalangeal, tarsometatarsal, cuboid metatarsal, talonavicular, calcaneocuboid, and subtalar joints on each foot. If present, total volumes of tophi in both feet were quantified using an automated software program of DECT. <h3>Results</h3> Of 264 foot joint areas examined, tophi were detected in 24 joints (9.1%) by DECT, whereas no tophi were detected by plain radiographs. The mean total volume of tophi per patient was 0.77±0.71cm<sup>3</sup>, and mean 4.0±2.8 joint areas per patient were positive for tophi detected by DECT. Most common site for tophi was 1st MTP (45.8%). Four patients had tophi detected in asymptomatic joints. <h3>Conclusions</h3> DECT has excellent detection of subclinical tophi in gout patients who had no apparent tophi on physical examination. DECT is a promising tool for accurate and early detection of tophi in a noninvasive manner. <h3>References</h3> Choi HK, Al-Arfaj AM, Eftekhari A, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis 2009;68:1609–12. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3448
Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41
Authors: Ashley A. Basiorka, Kathy L. McGraw, Leentje De Ceuninck, Lori N. Griner, Ling Zhang, Justine A. Clark, Gisela Caceres, Lubomir Sokol, Rami S. Komrokji, Gary W. Reuther, Sheng Wei, Jan Tavernier, Alan F. List
Journal: Cancer Research (2016)

In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Rα receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531-40. ©2016 AACR.
TAILORING THERAPY IN ACUTE HEART FAILURE: CAN BIOMARKERS DISTINGUISH RESPONDERS FROM NON-RESPONDERS?
Authors: Licette Liu, Mattia A.E. Valente, Douwe Postmus, Christopher O’Connor, Marco Metra, Piotr Ponikowski, John Teerlink, Gad Cotter, Beth Davison, John Cleland, Michael Givertz, Daniel Bloomfield, Dirk van Veldhuisen, Hans Hillege, Peter van der Meer, Adriaan Voors
Journal: Journal of the American College of Cardiology (2015)
AB1120 Juvenile dermatomyositis: A MRI scoring system to assess acute inflammation and damage
Authors: S. Breton, K. Lambot, C. Elie, P. Quartier, C. Wouters, C. Gitiaux, C. Bodemer, F. Brunelle, B. Bader-Meunier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Magnetic Resonance Imaging (MRI) is a very sensitive method to demonstrate muscle inflammation, but there is no standardized scoring system to assess both inflammation and damage in juvenile dermatomyositis <h3>Objectives</h3> To propose and to validate a MRI scoring system assessing acute inflammation and damages findings in Juvenile Dermatomyositis (JD). <h3>Methods</h3> Children with JD referred to our institution for proximal thighs MRI between 1998 and 2009 were retrospectively included. The MRIs were analysed twice by two musculoskeletal paediatric radiologists with a 6 weeks interval. Inflammatory activity was scored including muscle œdema (0=none, 1=mild and 2=severe), fascial, subcutaneous fat and skin œdema (qualitative scale). Damages were scored including calcinosis in muscles, fascias, subcutaneous fat and skin (qualitative scale), muscle and fat atrophy (qualitative scale) and muscle fatty infiltration (0=none, 1=mild and 2=severe). <h3>Results</h3> 20 children were included (median age, 7.1 years; range, 1-15; 6 boys and 14 girls). 45 MRI were analysed, which 10 were performed in the 2 months diagnosis. The most common MRI findings were muscle œdema (80%) regarding inflammatory activity, and muscle fatty infiltration (24%) regarding damages. Both intra- and inter-observers agreements were excellent regarding global score (Intraclass Correlation Coefficient [ICC], from 0.95 [CI 95%, 0.87-0.98] to 0.97 [0.94-0.99] and 0.88 [0.74-0.95], respectively). Inter-observer ICC were also excellent regarding inflammatory and damage subscores (0.84 [0.73-0.91] and 0.89 [0.66-0.97], respectively). <h3>Conclusions</h3> MRI is a reliable and reproductible tool for analysing inflammatory activity and damage during JD. <h3>Disclosure of Interest</h3> None Declared
Case 44-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, H.M. Heller, J.F. Southern
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 60-year-old man was admitted to the hospital because of chronic diarrhea and increasing weakness.The patient was in stable health until eight months earlier, when diarrhea developed while he was working in Mexico. A test for antibodies to human immunodeficiency virus (HIV) type 1 was positive. He returned to this country. Seven and a half months before entry he noticed weakness of the right leg and clumsiness of the right arm. One month later he came to this hospital, where physical examination revealed spastic paresis of the right leg. A cranial computed tomographic (CT) scan showed . . .
BRCA1 Alteration Found in Eastern European Jews
Authors: B. Kuska
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article BRCA1 Alteration Found in Eastern European Jews Get access Bob Kuska Bob Kuska Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Page 1505, https://doi.org/10.1093/jnci/87.20.1505 Published: 18 October 1995
Residents' Response to Duty-Hour Regulations — A Follow-up National Survey
Authors: Brian C. Drolet, Derrick A. Christopher, Staci A. Fischer
Journal: New England Journal of Medicine (2012)

The Accreditation Council for Graduate Medical Education implemented new requirements for resident duty hours and supervision in July 2011. This survey examines whether residents' concerns about potential effects on education and patient care have been borne out.
FRI0460 Pulmonary Fibrosis in Anca-Associated Vasculitis: Clinical Characteristics and Long-Term Followup of 49 Patients
Authors: C. Comarmond, B. Crestani, A. Tazi, B. Hervier, S. Adam Marchand, H. Nunes, F. Cohen-Aubart, M. Wislez, J. Cadranel, B. Housset, C. Lloret-Linares, P. Sève, C. Pagnoux, S. Abad, J. Camuset, B. Bienvenu, M. Duruisseaux, E. Hachulla, J.-B. Arlet, M. Hamidou, A. Mahr, M. Resche-Rigon, A.-L. Brun, P. Grenier, P. Cacoub, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Pulmonary fibrosis (PF) is a rare manifestation observed in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA). <h3>Objectives</h3> To report long-term outcome of a cohort of patients with the uncommon association of PF and AAV. <h3>Methods</h3> We performed a retrospective multicentric study of characteristics and outcome of patients with PF associated to AAV, fulfilling the ACR and/or Chapel Hill definitions. <h3>Results</h3> Forty nine patients [30 (61%) men, median age at diagnosis of AAV of 68 [58–73] years] with PF associated to AAV were identified. Forty (81.6%) patients had microscopic polyangiitis and 9 (18.4%) had granulomatosis with polyangiitis. The diagnosis of PF preceded the onset of vasculitis in 22 (45%) patients. Usual interstitial pneumonia was the main radiological pattern (n=18, 43%). ANCA were mostly of anti-myeloperoxydase specificity (88%). All patients were treated with steroids as induction therapy, combined with cyclophosphamide (CYC) (n=36, 73.5%) or rituximab (RTX) (n=1, 2%). Factors associated with mortality included occurrence of chronic respiratory insufficiency (HR 7.44, 95% CI (1.6 to 34.5), P=0.003), older age at PF diagnosis (HR 1.08, (1.02-1.13), P=0.005), and a higher eosinophil count at AAV diagnosis (HR 1.32, (1.07-1.63), P=0.0084). The 3-year survival rate in patients treated with steroids alone or combined with immunosuppressant (CYC or RTX) as induction therapy was of 64% (95% CI, 41-99) and 94% (95% CI, 86-100), respectively (<i>P</i>=0.03, Fig. 1). After a median follow-up of 48 [14–88] months, eighteen (37%) patients died, including 11 related to respiratory insufficiency. <h3>Conclusions</h3> PF is a rare manifestation of AAV with a very poor prognosis. Induction therapy with CYC might improve the outcome. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4159
Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells
Authors: H Engel, J Drach, A Keyhani, S Jiang, NT Van, M Kimmel, G Sanchez-Williams, A Goodacre, M Andreeff
Journal: Leukemia (1999)
Abstract P4-01-08: Effect of bilateral salpingo-oophrectomy on breast MRI fibroglandular volume and background parenchymal enhancement for BRCA 1/2 mutation carriers.
Authors: MJ De Leo, S Domchek, D Kontos, E Conant, S Weinstein
Journal: Cancer Research (2012)

Abstract PURPOSE: Bilateral salpingo-oophrectomy (BSO) reduces breast cancer risk in women with BRCA1/2 mutations by approximately 50%. Annual screening for these high-risk women includes breast MRI and mammography. It is unknown whether BSO affects fibroglandular volume (FG) and background enhancement (BG) on breast MRI in this population. The purpose of this study is to assess the difference in FG and BG in BRCA1/2 mutation carriers before and after BSO on breast MRI. METHOD AND MATERIALS: We compared FG and BG on contrast-enhanced breast MRI before and after BSO. Two readers blinded to both clinical and imaging history scored FG according to the BI-RADS criteria from 1–4: fatty, scattered, heterogeneously dense, or extremely dense. BG was graded based on the MRI BI-RADS scale from 1–4: minimal, mild, moderate, and marked. Average BIRADS scores of each reader were used to calculate mean FG and BG (±SD) before and after BSO, and compared using a paired t-test for significance. RESULTS: We examined 60 women with BRCA1/2 mutations who underwent breast MRI before and after BSO from 2001–2011 at our institution. Five patients were excluded from the final analysis as they underwent mastectomy or bilateral radiation therapy before post-BSO MRI. Mean time to post-BSO MRI was 8.3 months ± 7 months. Mean pre- and post-operative FG were 2.64±0.78 and 2.58±0.75, respectively (p = 0.622). Mean pre- and post-operative BG were 2.46±0.93 and 1.87±0.81, respectively (p = 0.0001). Breast cancer was detected in 8 women at a median time of 3.4 years following BSO. In these 8 women, mean pre- and post-operative FG were 3.10±0.57 and 2.55±0.69, respectively. Mean pre- and post-operative BG were 3.20±0.67 and 2.35±0.71, respectively. CONCLUSION: In this population of 55 BRCA1/2 mutation carriers who underwent breast MRI before and after BSO, there was a significant reduction in BG following BSO. There was no difference in FG on MRI following BSO. For the 8 patients in this cohort who were diagnosed with breast cancer after BSO, there was a trend toward higher FG and BG both before and after BSO, in comparison to the patients who were not diagnosed with breast cancer, suggesting that rates of higher FG and BG may be associated with increased risk for developing breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-08.
FIBROBLAST GROWTH FACTOR-23 AND CARDIAC MRI INDICES OF MYOCARDIAL FIBROSIS IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Mohamed Faher Almahmoud, David Herrington, W. Hundley, Jennifer Jordan, Bryan Kestenbaum, Ronit Katz, Erin Michos, Chia-Ying Liu, Bharath Ambale Venkatesh, Joao Lima
Journal: Journal of the American College of Cardiology (2016)
THU0462-HPR Cognitive processes for rating fatigue: What the numbers don’t tell us
Authors: K.S. Miljeteig, J. Harris, A.K. Kongtorp
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patient involvement has been an important part of the recent development of a validated instrument for rating RA fatigue. There has been no research, however, on the cognitive processes that patients use when they try to assign ratings for the severity of their condition. Quality of life researchers have noted this gap. <h3>Objectives</h3> Our qualitative study explored the challenges for patients when using a Visual Analogue Scale. <h3>Methods</h3> Semi-structured cognitive interviewing was used to explore participants' thought processes as they tried to complete the rating scale. Interviews were transcribed and preliminary analysis was conducted by two of the authors. Emerging themes were translated into English and further analysed by all authors. <h3>Results</h3> Four themes emerged: finding a common language, evaluating fatigue in context, trying to find a pattern, and fiddling with the numbers. <h3>Conclusions</h3> Patients experienced difficulties is assigning a summary score for a condition that can vary hourly. When they arrived at an average score, they then compared their rating with the experiences of others, and in some cases adjusted their scores to conform what they perceived to be socially acceptable norms. Patients also noted that a commonly understood description for RA fatigue does not exist. Lack of a common terminology makes it difficult for patients, clinicians and researchers to rate the severity of fatigue. We suggest that the value of rating scales lies in their ability to trigger discussion about fatigue experiences, and that discussion as well as a fatigue score need to be considered by nurses when working with RA patients. <h3>Disclosure of Interest</h3> None Declared
Catechol Amine and Psychologic Correlates of Vascular Responses
Authors: George D. Zuidema, Albert J. Silverman, Sanford I. Cohen, McChesney Goodall
Journal: New England Journal of Medicine (1957)

THE relation of acute and chronic emotional stresses to vascular responses has been repeatedly observed. This relation has been attributed to the firing of cortical impulses into lower centers regulating cardiovascular activity. Autonomie activity and humoral discharges have been implicated as the mediators of vascular responses activated by cortical and hypothalamic areas. However, a major difficulty has been the establishing of exact psychophysiologic correlates in relating psychologic events, biochemical changes and vascular responses.Funkenstein's1 work associated the outward expression of anger with blood-pressure increases and secretion of nor-epinephrinelike substances. On the other hand, anxiety or anger directed at oneself was . . .
SMALL DENSE LOW-DENSITY LIPOPROTEIN (LDL) PARTICLE NUMBER PREDICTS VASCULAR INFLAMMATION INDEPENDENT OF TRADITIONAL LIPID CARDIOVASCULAR RISK FACTORS IN PSORIASIS
Authors: Nehal N. Mehta, Balaji Natarajan, Martin Playford, Joseph Lerman, Mohammad Tarek Kabbany, Tsion Aberra, Qimin Ng, Heather Teague, Justin Rodante, Aditya Joshi
Journal: Journal of the American College of Cardiology (2016)
σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury
Authors: Adam Hosszu, Zsuzsanna Antal, Lilla Lenart, Judit Hodrea, Sandor Koszegi, Dora B. Balogh, Nora F. Banki, Laszlo Wagner, Adam Denes, Peter Hamar, Peter Degrell, Adam Vannay, Attila J. Szabo, Andrea Fekete
Journal: Journal of the American Society of Nephrology (2016)

Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinity σ1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt-mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.
Reply to the letter to the editor ‘Insertion of central venous catheters (CVCs): any changes in the past ten years’ by Biffi et al.
Authors: D. Pinto, P. Gouveia, B. Sousa, M. Hutka, J. Furlanetto, J.M. Mariz, R. Wuerstlein, F. Cardoso
Journal: Annals of Oncology (2016)