tbuckley/cabot-search huggingface dataset:
Erratum: Corrigendum: Transcriptional regulator PRDM12 is essential for human pain perception
Authors: Ya-Chun Chen, Michaela Auer-Grumbach, Shinya Matsukawa, Manuela Zitzelsberger, Andreas C Themistocleous, Tim M Strom, Chrysanthi Samara, Adrian W Moore, Lily Ting-Yin Cho, Gareth T Young, Caecilia Weiss, Maria Schabhüttl, Rolf Stucka, Annina B Schmid, Yesim Parman, Luitgard Graul-Neumann, Wolfram Heinritz, Eberhard Passarge, Rosemarie M Watson, Jens Michael Hertz, Ute Moog, Manuela Baumgartner, Enza Maria Valente, Diego Pereira, Carlos M Restrepo, Istvan Katona, Marina Dusl, Claudia Stendel, Thomas Wieland, Fay Stafford, Frank Reimann, Katja von Au, Christian Finke, Patrick J Willems, Michael S Nahorski, Samiha S Shaikh, Ofélia P Carvalho, Adeline K Nicholas, Gulshan Karbani, Maeve A McAleer, Maria Roberta Cilio, John C McHugh, Sinead M Murphy, Alan D Irvine, Uffe Birk Jensen, Reinhard Windhager, Joachim Weis, Carsten Bergmann, Bernd Rautenstrauss, Jonathan Baets, Peter De Jonghe, Mary M Reilly, Regina Kropatsch, Ingo Kurth, Roman Chrast, Tatsuo Michiue, David L H Bennett, C Geoffrey Woods, Jan Senderek
Journal: Nature Genetics (2015)
Abstract 1100: Dynamic multicellular mechanics controlling protrusion in 3D.
Authors: Timothy Fessenden, Margaret L. Gardel
Journal: Cancer Research (2013)

Abstract Despite much effort, the transition from benign to malignant breast cancer remains poorly understood, resulting in overtreatment of women with in situ lesions. A growing appreciation for the role of cell mechanics in driving cell behavior has prompted interest in how mechanical interactions might control tumor growth and progression. How these parameters impact the transition from benign to malignant breast cancer remains unclear. Mechanical interactions among cells via adherens junctions, and between cells and the ECM via focal adhesions, can each exert dominant effects on cell behavior. Cell motility and invasion require force interactions by harnessing cytoskeletal dynamics, which permit shape changes and generate and transmit forces. Tension maintained across the actin cortex mechanically restricts protrusions, and may be transmitted across multiple cells via adherens junctions. Thus epithelial cells form mechanically integrated tissues that may be responsive to changes in cortical tension over great distances. However, the regulatory role of cortical tension in restricting cells from protruding is unclear. Overall, we lack detailed morphologic and mechanical models of cell protrusion and invasion out of 3D collectives. Using MDCK cell exposure to HGF as a model for rupture of epithelial integrity and protrusion, we have demonstrated the morphologic parameters that permit protrusion of a cell from its surrounding epithelium. Combined with work from our lab on force interactions between cells via adherens junctions, as well as mechanical interactions between a cell and its substrate, we may extrapolate detailed force interactions that underlie the observed cell shape and motility parameters that permit protrusion. Citation Format: Timothy Fessenden, Margaret L. Gardel. Dynamic multicellular mechanics controlling protrusion in 3D. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1100. doi:10.1158/1538-7445.AM2013-1100
CONDUCTANCE CATHETER DERIVED RIGHT VENTRICULAR DYSFUNCTION IS EVIDENT AFTER BALLOON EXPANDABLE TRANSCUTANEOUS AORTIC VALVE REPLACEMENT IN HUMANS
Authors: Richard Graham Axell, Paul A. White, Bushra S. Rana, Andrew Klein, Michael O’Sullivan, Lenoard M. Shapiro, Cameron G. Densem, Stephen Hoole
Journal: Journal of the American College of Cardiology (2015)
Incremental Diagnostic Value of F-18 FDG PET/CT Over MRI in a Pediatric Patient With Suspected Hepatoblastoma and Histologic Diagnosis of Focal Nodular Hyperplasia
Authors: Francesco Bertagna, Emanuela Orlando, Giovanni Bosio, Luisa Bercich, Simona Fisogni, Luigi Grazioli, Raffaele Giubbini
Journal: Clinical Nuclear Medicine (2011)

Hepatoblastoma (HB) is the most common pediatric liver cancer representing 1% of all pediatric malignances and occurring mostly within 5 years of age. Liver recurrences and secondary lesions (abdomen, lung, and brain) can occur. Surgery and chemotherapy are widely accepted. Focal nodular hyperplasia (FNH) is a benign, usually asymptomatic, and incidental hepatic tumor with an unclear etiology, good prognosis, and its clinic management should be conservative. FNH could be evaluated by ultrasonography, computed tomography, and magnetic resonance imaging. Nuclear medicine procedures do not have an effective role in evaluating HB/FNH but F-18 FDG PET/CT represents a new option. We report a case of a child with a lesion suspect for HB at magnetic resonance imaging and negative F-18 FDG PET/CT with histologic diagnosis of FNH after resection.
AB0400 Eros study –erosions as rheumatoid arthritis outcomes and biologics
Authors: L. Cunha-Miranda, C. Rodrigues, S. Fernandes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In RA, many different clinical and biochemical variables and composite measures reflect the degree of inflammation in the joints. Joint inflammation can lead to joint destruction in most patients. Joint destruction is considered a key outcome in RA and is linked to the worsening of HAQ. One of the claimed breakthroughs of biologic agents is their potential to arrest radiographic progression but is this clinical relevant on the daily practice to consider starting a biologic? <h3>Objectives</h3> Assess the main reasons for biologic therapy introduction in RA patients and the relevance of radiological progression on the selection of patients for biological therapies. <h3>Methods</h3> Development and implementation of a questionnaire among Portuguese Hospital-based Rheumatologists in order to collect data regarding the reasons they consider important when starting biological therapies in RA patients. This questionnaire also evaluated the impact of radiological progression on starting biological therapy decision <h3>Results</h3> 31 rheumatologists answered the questionnaire (about 25-30% of the Portuguese hospital-based rheumatologists); 17 female (55%) with a mean age of 42.7±9.3 years (var: 31-60 years). The mean average time as a specialist was 9.9±7.8 years (var: 1-25 years). The answers to question ``Choose 2 from a total of 6 reasons for prescribing biological therapy99 were: 29 DMARDs failure; 19 maintain disease activity; 3 meets the SPR criteria; 3 radiological progression; 2 physical and psychological disability; 1 young and active patient. When asked about the clinical importance of radiological progression: 11 classified as extremely important; 15 very important, 4 important; 1 less important and 0 answered no importance. Another question included in this questionnaire was ``On the last 100 AR patients observed, in how many times have you assessed the radiological progression through the Total Sharp Score method?99 25 didn9t applied to any patient, 3 applied to 1 patient, 2 applied to 2 patients and 1 applied to 10 patients. So, for a potential number of 3100 patients observed, 17 were evaluated for the radiological damage (0.5%). <h3>Conclusions</h3> There is scientifically data demonstrating the importance of radiological progression evaluation; but in the clinical practice this isn9t possible. The radiological progression evaluation methods are difficult to apply and time consuming, so they have been losing their relevance in daily clinical practice. The main reasons for the rheumatologist to start biological therapy are increased disease activity and failure of synthetic DMARD9s, that are known to been intimately connect with radiological progression. Alternative methods should be developed, such as risk matrices and therapeutic strategies, in order to evaluate radiological progression, allowing a better and adequate management for RA patients. <h3>Disclosure of Interest</h3> None Declared
1380 HYPERFERRITINEMIA: PHENOTYPIC CHARACTERISTICS, RELEVANCE OF HFE MUTATIONS AND MAGNETIC RESONANCE AMONG OUTPATIENT REFERRALS FOR ELEVATED SERUM FERRITIN
Authors: A. Castiella, E. Zapata, L. Zubiaurre, J.M. Alústiza, M.D. De Juan, A. Aguirre, J.I. Emparanza, P. Otazua
Journal: Journal of Hepatology (2012)
Diagnostic accuracy of endoscopic ultrasonography in preoperative assessment of early gastric cancer
Authors: BD Ye, SG Kim, JH Cheon, HJ Lee, JS Kim, HK Yang, JK Han, WH Kim, HC Jung, IS Song
Journal: Endoscopy (2006)

Background and Aims: Recently, laparoscopy-assisted gastrectomy (LAG) has been more widely performed for early gastric cancer (EGC). Preoperative accurate evaluation for primary lesions regarding depth of invasion is important for LAG, but multidetector row computed tomography (MDCT) is not sufficient for evaluation of primary lesions in cases of EGC. This study was performed to evaluate the preoperative diagnostic role of endoscopic ultrasonography (EUS) for EGC.
P5-23-04: Gonadotrophin-Releasing Hormone Analogues for Ovarian Function Preservation in Women with Premenopausal Breast Cancer Undergoing Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis.
Authors: MRS Cruz, E Motta, EMK Silva, SG Bernardo, AN Atallah
Journal: Cancer Research (2011)

Abstract Background: Breast cancer, the most common female malignancy, is also the most frequent tumor in women of reproductive age. Young women with breast cancer usually present adverse prognostic features and higher rates of recurrence when compared with their older counterparts. Adjuvant chemotherapy is usually recommended for this group of patients and premature ovarian failure (POF) is a potential complication. Material and Methods: We conducted a systematic search in MEDLINE, EMBASE, Cochrane Systematic Reviews databases and ***ClinicalTrials.gov from their inception until June 2011. The search was conducted to include published peer-reviewed studies on the issue of fertility preservation in women with breast cancer undergoing adjuvant chemotherapy. The search terms were tailored individually for each database to include the following Medical Subject Headings (MeSH) and text words: gonadotropin releasing hormone, breast neoplasms, drug therapy, premature ovarian failure and fertility. No language restriction was applied. We also searched for additional studies by reviewing the reference lists of retrieved articles, and studies presented in abstract form were also located in this manner. The main outcomes were return of spontaneous menstruation, ovulation and pregnancy rate. Results: We found 8 RCTs that met the inclusion criteria. Data were extracted from 3 RCTs. Data were only available for resumption of ovulation. There were no data available for markers of ovarian function, rate of ovulation and pregnancy. The rate of women with spontaneous menstruation demonstrated a statistically significant difference in favor of the use of GnRH-a (OR 3.11;95% CI, 2.04-472). Discussion: Use of GnRH concomitant to adjuvant chemotherapy in premenopausal breast cancer women aiming to reduce rates of POF has been subject of controversy during the last decade. Evidence from recently presented RCTs suggests there is a benefit of GnRH for ovarian function protection in this setting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-04.
P5-02-01: ErbB4 Ectodomain as a Biomarker and a Potential Therapeutic Target for Breast Cancer.
Authors: M Hollmen, P Liu, H Wildiers, I Reinvall, T Vandorpe, A Smeets, K Deraedt, T Vahlberg, H Joensuu, D Leahy, P Schoffski, K Elenius
Journal: Cancer Research (2011)

Abstract ErbB4 function is controversial in breast cancer and influenced by alternative splicing of the ERBB4 gene. Here we evaluated the cleavable ErbB4 JM-a isoform as a potential drug target and biomarker. To address ErbB4 cleavage in breast cancer tissues in vivo, extracellular and intracellular cleavage products of ErbB4 were assessed by ELISA and immunohistochemistry using matched serum and tissue samples from a series of 243 breast cancer patients. Elevated serum ectodomain level (≥40 ng/mL) and nuclear immunoreactivity were present in 21% and 52% of the patients, respectively. An elevated serum ErbB4 ectodomain concentration was not associated with tumor nuclear immunoreactivity, but was significantly associated with the premenopausal status at diagnosis (P = 0.04). Estradiol also enhanced ErbB4 cleavage and ErbB4 cleaving enzyme activity in vitro, supporting a role for estrogen signaling in regulation of ErbB4 cleavage. Selective targeting of the cleavable ErbB4 JM-a in human breast cancer cells with an ErbB4 isoform-specific mAb 1479 inhibited ErbB4 cleavage and reduced tumor formation in a mouse xenograft model. Consistent with blocking of ErbB4 cleavage, mutagenesis studies and the 3.4 Å X-ray crystal structure of a complex of the ErbB4 extracellular region and the 1479 Fab localized the binding site of mAb 1479 on ErbB4 to a region on subdomain IV encompassing JM-a-specific residues. These data demonstrate that ErbB4 is cleaved in a subset of breast cancer patients, and suggest that the mechanisms by which mAb 1479 suppresses breast cancer cell growth involves inhibition of ErbB4 cleavage. Serum ErbB4 ectodomain concentration could be used as a biomarker to monitor the activity of compounds, such as mAb 1479, that target ErbB4 cleavage. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-02-01.
Expenditures and Prices of Antihyperglycemic Medications in the United States: 2002-2013
Authors: Xinyang Hua, Natalie Carvalho, Michelle Tew, Elbert S. Huang, William H. Herman, Philip Clarke
Journal: JAMA (2016)

A recent study demonstrated widespread substitution of analog for human insulin and rising out-of-pocket costs in privately insured people with type 2 diabetes in the United States.1 Medicaid reimbursements have increased for both human insulin and more costly analog insulins.2 Although studies have described per-person changes in excess medical spending of US adults with diabetes on prescription medications,3 they have not reported trends in expenditures for different classes of antihyperglycemic medications that simultaneously consider changes in use and price.
Abstract 3604: Significant effect of polymorphisms in CYP2D6 and DT-1 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients
Authors: Hitoshi Zembutsu, Kazuma Kiyotani, Taisei Mushiroda, Chiyo K. Imamura, Naoya Hosono, Michiaki Kubo, Yusuke Tanigawara, David A. Flockhart, Todd C. Skaar, Zeruesenay Desta, Fuminori Aki, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura
Journal: Cancer Research (2010)

Abstract PURPOSE: The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism and elimination of its active forms. We investigated relations of polymorphisms in transporter genes as well as CYP2D6 to clinical outcome of patients with tamoxifen treatment. PATIENTS AND METHODS: We enrolled 282 hormone receptor-positive, invasive breast cancer patients receiving tamoxifen monotherapy. We investigated the effects of allelic variants of CYP2D6 and tag-SNPs of DT-1, DT-2 and DT-3 on recurrence-free survivals using Kaplan-Meier and Cox regression analyses. Plasma concentrations of tamoxifen metabolites were measured in 98 patients taking 20 mg/day of tamoxifen. RESULTS: CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = 3.6×10−5; hazard ratio (HR) 9.52 [95% CI 2.79-32.45] in patients with 2 variant alleles vs without variant allele). Among 51 tag-SNPs in transporter genes, a significant association was found at SNPY in DT-1(P = 1.7×10−4; HR 10.64 [95% CI 1.44-78.88] in patients with AA vs GG genotypes). The number of risk alleles of CYP2D6 and DT-1 showed cumulative effects on recurrence-free survivals (P = 5.5×10−8). The patients carrying 4 risk alleles had 45.25-times higher risk compared to those with ≤1 risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = 4.3×10−6 and 5.2×10−4), whereas no significant difference was found among DT-1 genotype groups. CONCLUSION: Our results indicated that polymorphisms in CYP2D6 and DT-1 are important predictors for the prognosis of breast cancer patients treated with tamoxifen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3604.
Early Gastric Cancer in Young, Asymptomatic Carriers of Germ-Line E-Cadherin Mutations
Authors: David G. Huntsman, Fatima Carneiro, Frank R. Lewis, Patrick M. MacLeod, Allen Hayashi, Kristin G. Monaghan, Raymond Maung, Raquel Seruca, Charles E. Jackson, Carlos Caldas
Journal: New England Journal of Medicine (2001)

Germ-line truncating mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer.
DS-01 * GLUCOCORTICOIDS POTENTLY INDUCE APOPTOSIS IN THE CEREBELLAR EXTERNAL GRANULE LAYER: IMPLICATIONS FOR MEDULLOBLASTOMA TREATMENT
Authors: O. Cabrera, B. Swiney, J. Smith, N. Farber, K. Noguchi
Journal: Neuro-Oncology (2014)

Premature infants suffering from respiratory dysfunction are often administered glucocorticoids (GCs) to mature the lungs. Unfortunately, neonates exposed to GCs can exhibit neuromotor deficits and selective cerebellar stunting. In order to test the safety of GCs, we administered the synthetic GC dexamethasone to neonatal mouse pups and found it potently increased apoptosis in the external granule layer (EGL) of the cerebellum. The EGL is responsible for producing over 90% of the neurons in the cerebellum, which represents over half the neurons in the entire brain. We subsequently discovered that endogenous GC release, receptors, and enzymatic metabolism is carefully orchestrated to selectively increase stimulation in the EGL as it is naturally eliminated. This suggests the GC system may signal the permanent disappearance of the EGL during development. Unfortunately, EGL neural progenitor cells (NPCs) can transform into medulloblastomas (MBs), the most common malignant brain tumor in children. As a result, the GC system may play a critical role in MB development. Up to 30% of human medulloblastomas are thought to be driven by excessive Hedgehog signaling (a potent EGL mitogen). Consistent with this idea, mice with mutations causing constitutive Hedgehog signaling are also vulnerable to MB formation. Interestingly, excessive Hedgehog signaling is also thought to decrease GC stimulation in the EGL due to selective GC metabolism. Therefore, we used MB prone (Patched) mice to examine if this vulnerability still exists during preneoplastic tumor transformation. We found GC stimulation potently increased apoptotic cell death in preneoplasms. This suggests GCs may both play a role in MB development and have potential as a therapeutic treatment.
ELECTROCARDIOGRAPHIC PR SEGMENT DEPRESSION IN V1 IS ASSOCIATED WITH SUDDEN CARDIAC DEATH IN ASYMPTOMATIC ADULTS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: David German, Muammar Kabir, Elyar Ghafoori, Tor Biering-Sorensen, Jonathan Waks, Sunil Agarwal, Dan Arking, Nona Sotoodehnia, David Siscovick, Wendy Post, Charles Henrikson, Scott Solomon, Elsayed Soliman, Josef Coresh, Mark Josephson, Larisa Tereshchenko
Journal: Journal of the American College of Cardiology (2015)
Scintigraphic Assessment of Patients with Electrocardiographic Left Ventricular Hypertrophy with ST-T Changes Without Apparent Cause
Authors: MICHIHIRO NARITA, TADASHI KURIHARA
Journal: Clinical Nuclear Medicine (2002)

Purpose Some patients who show electrocardiographic left ventricular hypertrophy with ST-T changes (ECG-LVH) are difficult to evaluate using routine examinations. To clarify the pathologic process in these patients, the authors performed several scintigraphic examinations. Materials and Methods Twenty-nine patients with ECG-LVH, without apparent cause, such as left ventricular (LV) systolic overloading or increased LV mass, were examined by myocardial I-123 MIBG imaging, I-123 BMIPP imaging, and exercise-induced stress perfusion imaging. In addition to the visual assessment of each image, we calculated global and regional myocardial washout of I-123 MIBG (%washout). The LV was assessed using conventional echocardiography. Results Visually observed abnormalities were located exclusively at the LV apex with all imaging methods and were detected in 76%, 52%, and 17% of patients by I-123 MIBG, I-123 BMIPP, and perfusion imaging, respectively. A follow-up study revealed that the apical defects of I-123 MIBG were subsequently followed by defects of I-123 BMIPP and then perfusion abnormalities. In patients with an apical defect revealed by I-123 MIBG imaging, apical %washout was high. In nine patients who underwent myocardial biopsy, myocardial disarray was observed at the apical regions. Conclusions In many patients with ECG-LVH without apparent cause, sympathetic abnormalities are observed at the apex, similar to pathologic changes in hypertrophic cardiomyopathy. These abnormalities may lead to changes in fatty acid metabolism and perfusion.
Double-balloon endoscopy versus magnet-imaging enhanced colonoscopy for difficult colonoscopies, a randomized study
Authors: T. Suzuki, M. Matsushima, Y. Tsukune, M. Fujisawa, T. Yazaki, T. Uchida, S. Gocyo, I. Okita, K. Shirakura, K. Sasao, T. Saito, I. Sakamoto, M. Igarashi, J. Koike, A. Takagi, T. Mine
Journal: Endoscopy (2011)

<b>Background and study aims:</b> Studies have estimated that failure of cecal intubation occurs with conventional colonoscopy in up to 10 % of cases. Double-balloon endoscopy (DBE) systems, magnetic endoscope imaging (MEI), and transparent cap have been shown to improve success rates for colonoscopy. This study evaluated the utility of DBE for complete examination of the colon compared with MEI plus cap (MEI-Cap) after incomplete or technically difficult colonoscopy in a randomized comparative manner. <b>Patients and methods:</b> A total of 94 patients with incomplete or technically difficult colonoscopy were randomly assigned to receive either DBE (n = 47) or colonoscopy with MEI–Cap (n = 47). The primary end point was cecal intubation rate within 30 minutes. Secondary end points included intubation time, pain score using a visual analog scale, abdominal pressure attempts, doses of sedative medication, and changes in patient position during colonoscopy. <b>Results:</b> Patient characteristics were comparable in both groups. Cecal intubation rate within 30 minutes was significantly higher for DBE (45 /47, 95.7 %) than for MEI–Cap (34 /47, 72.3 %) (<i>P</i> = 0.0049). Mean time to reach the cecum was significantly lower in the DBE group (13.0 ± 5.3 minutes) than in the MEI–Cap group (16.4 ± 4.8 minutes; <i>P</i> = 0.0003). No complications were encountered in either group. <b>Conclusion:</b> DBE is more useful for complete examination of the colon than MEI–Cap in patients with incomplete or technically difficult colonoscopy.