tbuckley/cabot-search huggingface dataset:
SAT0364 Are differences of hip shape responsible for increased femoral neck fracture risk in post-menopausal women?:
Authors: A.G.S. Oldroyd, M. Nickkho-Amiry, B. Evans, C. Greenbank, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Studies have identified the relationship between the menopause and femoral neck fracture risk. Recent research has implicated proximal femoral shape, measured using Hip Structural Analysis (HSA), in femoral neck fracture risk. It is not known if detrimental changes of proximal femur shape during the menopause confound reduction of bone mineral density, thus increasing femoral neck fracture risk. <h3>Objectives</h3> This study aims to investigate the influence of menopause upon proximal femur shape. <h3>Methods</h3> Data of pre and post-menopausal women attending for a DXA scan in a UK district general hospital between 2006 and 2010 were identified. Logistic regression analysis was used to compare HSA measurements, femoral neck t-score and previous low-trauma femoral neck fracture status between the pre and post-menopausal women; unadjusted then adjusted for possible confounders: age, body mass index (BMI). The following data were recorded: age, body mass index (BMI), previous low-trauma femoral neck fracture status, femoral neck t-score, all HSA measurements were collated: distance from centre of femoral head to centre of femoral neck (d1), distance from centre of femoral head to inter-trochanteric line (d2), mean femoral neck diameter (d3), distance from centre of mass of femoral neck to superior neck margin (y), hip axis length (HAL), cross-sectional moment of inertia (CSMI) and proximal femur strength index (SI). HSA measurements of individuals that had sustained a femoral neck fracture were taken from the contra-lateral hip. <h3>Results</h3> Compared to the pre-menopausal group (n=630), the post-menopausal (n=9372) group had a significantly higher mean age: 37.10 years (SD 0.26) vs 66.58 years (SD 0.10), a significantly higher mean BMI: 25.54 kg/m<sup>2</sup> (SD 0.25) vs 26.79 kg/m<sup>2</sup> (SD 0.05), a significantly lower mean femoral neck t-score: -0.34 (SD 0.04) vs -1.29 (SD 0.01) and a significantly higher proportion of individuals with a previous femoral neck fracture: 0.95% vs 3.10%, respectively. Logistic regression modelling, adjusted for age and BMI, indicated that post-menopausal status was significantly associated with a previous femoral neck fracture and a lower femoral neck t-score; no HSA measurement significantly differed between the pre and post-menopausal groups. <h3>Conclusions</h3> This study indicates that proximal femur shape is not implicated in the association between post-menopausal status and increased femoral neck fracture risk when age and BMI are taken into consideration. This study indicates that the reduction of BMD associated with the menopause is the most influential factor in femoral neck fracture risk. <h3>Disclosure of Interest</h3> None Declared
Abstract 1944: Phospholipid scramblase 1 and 3 as novel effectors of cripto-1 signaling
Authors: Hideaki Karasawa, Tadahiro Nagaoka, Maria Cristina Rangel, Nadia P. Castro, Natalie Held, Monica Gonzales, Caterina Bianco, David S. Salomon
Journal: Cancer Research (2011)

Abstract In the present study we performed a yeast two-hybrid (Y2H) screen to search for novel Cripto-1 (CR-1) binding proteins that might modulate CR-1-dependent signaling pathways involving Nodal/Gdf3/Smad 2/3 or GRP78/glypican-1/c-src. Screening a mouse embryo or human colon cDNA prey library with a peptide sequence of CR-1, we isolated six candidate genes, including mNotch3, mFibulin-4, mCHD4, hAHNAK, hHUWE1 and mouse phospholipid scramblase 3 (PLSCR3). PLSCRs consist of a family of four related genes that encode for endofacial transmembrane proteins, and have been proposed to play a role in the redistribution of plasma membrane phospholipids. Recent work on the PLSCRs has revealed their involvment in signal transduction and lipid metabolism. The most studied member of this family, PLSCR1, has been shown to partition into lipid rafts implicated in the regulation and endocytic trafficking of receptor-signaling complexes. We confirmed the results of the Y2H screen since we found that full-length GFP-tagged PLSCR1 and PLSCR3 were able to bind to 3xFLAG-CR-1 in transiently transfected 293T cells, as detected by coimmunoprecipitation and Western blot analysis. In addition, we were able to detect co-localization of these proteins in 293T cells that were transiently expressing GFP-PLSCR1/3 and 3xFLAG-CR-1 by immunocytochemistry. We then evaluated the effect of interaction between CR-1 and PLSCR-1/3 on Nodal signaling. We therefore analyzed the activity of the Nodal/Activin-responsive (n2)7-luciferase reporter ((n2)7-Luc), which contains mouse Fast-1 binding sites from the Nodal left side-specific enhancer, in 293T cells transiently expressing CR1-FLAG, PLSCR1-GFP, PLSCR3-GFP, (n2)7-Luc, TK-renilla, mouse Fast-1, mouse Nodal and human ALK4 expression vectors. Overexpression of PLSCR1 induced a very strong dose-dependent inhibition of CR-1 activation of Nodal-responsive luciferase reporter activity in 293T cells. In contrast, overexpression of PLSCR3 did not have a significant inhibitory effect on CR-1activation of Nodal-responsive luciferase reporter activity in 293T cells. The effect of knockdown of PLSCR-1/3 with specific siRNA on CR-1 ability to induce activation of a Nodal-responsive luciferase reporter assay and to modulate CR-1 Smad-dependent and Smad-independent signaling pathways is currently under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1944. doi:10.1158/1538-7445.AM2011-1944
Progression of Neonatal Herpes Simplex Meningoencephalitis Demonstrated by Sequential Tc-99m DTPA Brain Imaging
Authors: WEI-JEN SHIH, DARON G. DAVIS
Journal: Clinical Nuclear Medicine (1998)

Serial brain imaging with Tc-99m DTPA in a newborn with herpes encephalitis was performed 21 and 40 days after birth. Initial imaging showed increased right posterior parietal uptake, and the second study showed diffuse cerebral uptake. Thus, Tc-99m DTPA brain scans can detect, monitor, and possibly clinically predict herpes outcome in meningoencephalitis.
THE IMPACT OF INFLAMMATION ON REFLECTED WAVES AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Gerasimos Siasos, Manolis Vavuranakis, Eleni Kokkou, Maria Kariori, Mary Lavda, Sophia Vaina, Carmen Moldovan, Konstantinos Kalogeras, Evangelia Bei, Dimitrios Vrachatis, Konstantinos Mourouzis, Christodoulos I Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
AB0326 Characterizing Seronegative Rheumatoid Arthritis
Authors: I. Cobb, M. Antonelli, S.P. Ballou
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Seronegative Rheumatoid Arthritis (RA) is a disorder associated with considerable diagnostic, prognostic and therapeutic uncertainty for many clinicians. <h3>Objectives</h3> The aim of this study is to provide a deeper understanding of the diagnosis and manifestations of rheumatoid arthritis with negative serologies. <h3>Methods</h3> The study was a retrospective chart review of electronic medical records from January, 2003 to December, 2012. Patients were identified using ICD-9 code Rheumatoid Arthritis 714.0 and at least two rheumatology clinic visits during the specified time. Charts were reviewed individually by two investigators. The inclusion criteria were a diagnosis of RA confirmed by a rheumatologist with normal values for both rheumatoid factor (RF) and anti-CCP antibodies (CCP, third generation assay). Data were collected on demographics (sex, race, smoking status), family history of rheumatoid arthritis, and laboratory values (presence of anemia, inflammatory markers) at the time of diagnosis. The presence of erosions and synovitis identified by imaging studies was assessed. In addition, the presence of extra-articular manifestations of RA including nodules, pleural or parenchymal lung disease, eye involvement and osteoporosis was recorded. The therapies (DMARD, biologic) used to treat the seronegative RA were also reviewed. <h3>Results</h3> Charts from 108 patients were reviewed. Forty-five patients were excluded based on incorrect initial diagnosis or low clinical suspicion for seronegative RA by the rheumatologist. Sixty-three patients were included in this analysis. The demographics were similar to that of our patient population with seropositive RA. Of available data, at the time of diagnosis, 25% of the patients were smokers, 13% had a family history of RA, 54% were anemic, and 76% had abnormal ESR or CRP. Seven of the 63 (11%) patients had erosions on radiography, and 6 of 63 (9.5%) patients had MRI findings of synovitis. Initial data suggest that extra-articular manifestations are infrequent in this group. Forty-eight of the 62 were initiated on a DMARD, most commonly hydroxychloroquine (16% patients) or methotrexate (29% patients) with a large percentage of patients with combination of methotrexate and hydroxychloroquine therapy (35%). Of the 63 patients, 17 (27%) patients required a biologic therapy during treatment course. <h3>Conclusions</h3> This study supports the hypothesis that clinical history and physical examination are the most important determinants in diagnosing seronegative RA. In addition to characteristic symptoms, factors which might contribute to diagnosis of RA in a patient without seropositivity include positive family history, smoking history, acute phase reactants, presence of anemia, and imaging studies. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2163
Abstract 956: Cholesterol Crystals Cause Endothelial Damage and Impair Vasoreactivity
Authors: Nitesh Gadeela, Jack Rubinstein, Ameeth Vedre, Ruiping Huang, Andrew J Abela, George Abela
Journal: Circulation (2008)

Background Cholesterol has been shown to expand when crystallizing and then be released into the circulation following plaque rupture. We hypothesized that flow of sharp ended crystals in arteries could damage the intimal surface and decrease normal vasoreactivity. Methods Bilateral carotid arteries from seven NZW rabbits were placed in a dual perfusion chamber, preconstricted with nor-epinephrine (NE) and then challenged with acetylcholine (ACH) for endothelial reactivity and nitroprusside (SN) to evaluate for smooth muscle reactivity. Both arteries served as their own control and perfused with warm buffered saline solution (PBS). This was followed with PBS and cholesterol crystals (100–500 μm long) and then subjected to the same pharmacological challenge. Diameters were continually recorded and digitally measured at five sites in each artery and averaged. The intimal surface was then examined by scanning electron microscopy for cholesterol crystals and intimal damage. Results The vasoconstrictor and vasodilatory response to ACH -but not SN- was significantly decreased after crystals were infused in comparison to initial control measurements (Figure 1 ). On microscopic evaluation the intima infused with crystals demonstrated numerous sites of surface tears with evidence of cholesterol crystals perforating and embedding in the surface compared to normal controls. Conclusion Cholesterol crystals damaged endothelium and decreased vasoreactivity. The lack of significant change in response to SN suggests that this was due to intimal injury. These data have important clinical implications regarding impaired vasoreactivity during acute cardiovascular events.
Abstract 1262: Bif-1 is required for keeping mitochondrial and lysosomal positive feedback loops in check to prevent apoptosis induced by death receptors in type II cells
Authors: Sungman Park, Kimiyo Komine, Yoshinori Takahashi, Hong-Gang Wang
Journal: Cancer Research (2010)

Abstract Bif-1, also known as endophilin B1 and SH3GLB1, is involved in the regulation of apoptosis, mitochondrial morphogenesis, and autophagy. We have previously shown that increasing the levels of Bif-1 accelerates Bax conformational change, caspase-3 activation, and apoptotic cell death in response to a variety of intrinsic apoptotic stimuli, whereas the loss of Bif-1 delays all these processes. Here, we report the role of Bif-1 as a negative regulator in the extrinsic pathway of apoptosis by controlling mitochondrial and lysosomal amplification loops in type II cells. There are two different types of cells distinguished by their distinct extrinsic apoptotic signaling pathways. In type I cells, the activation of caspase-8 by death receptor ligation is sufficient to activate downstream effector caspases (e.g. caspaspe-3) for cell killing, whereas in type II cells, caspase cascade amplification through mitochondria and/or lysosome is required. We found that depletion of Bif-1 dramatically enhances not only caspase-3 but also caspase-8 activation and cell death in type II cell lines including MEF, HeLa, and Jurkat, but not in type I H9 cells, following treatment by the extrinsic apoptotic stimuli TNFα/cycloheximide, TRAIL or Fas ligand. Overexpression of Bcl-XL or XIAP in Bif-1 knockout MEFs significantly diminishes the enhanced caspase activation, indicating that a mitochondrial feedback loop is elevated by the loss of Bif-1. Moreover, while treatment with cathepsin inhibitors does not suppress TNFα/cycloheximide-induced caspase-3 activation in Bif-1 knockout MEFs, it completely blocks the activation of caspase-3 in Bif-1 knockout MEFs overexpressing Bcl-XL or XIAP, implying that lysosomal pathway is also involved. Furthermore, inhibition of caspase-8 is able to completely block the activation of caspase-3 induced by TNFα/cycloheximide, indicating that caspase-8 initiates the mitochondrial and lysosomal amplification loops observed in Bif-1 deficient type II cells. Taken together, these studies suggest that Bif-1 plays an important role in the regulation of caspase-8-initiated mitochondrial and lysosomal positive feedback loops for killing type II cells by death receptors. 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 1262.
Impact of fluoroscopy on oral double-balloon enteroscopy: results of a randomized trial in 156 patients
Authors: H. Manner, A. May, J. Pohl, M. Färber, C. Ell
Journal: Endoscopy (2010)

Background and study aims: The routine utility of fluoroscopy during double-balloon enteroscopy (DBE) via the oral route has been not prospectively evaluated. Up to now, there have been no prospective randomized trials to assess whether fluoroscopy improves outcomes. The aim of this study was to assess the value of fluoroscopy during oral DBE.
Breast cancer in the United States: the burden on an aging, changing nation.
Authors: BD Smith, GL Smith, A Hurria, TA Buchholz
Journal: Cancer Research (2009)

Abstract Abstract #6076 Background: Over the next 20 years, important demographic changes in the US will emerge, with the number of older and non-white Americans increasing dramatically. Though breast cancer incidence is known to vary by both age and race, the projected impact of impending population changes on breast cancer incidence has never been quantified. To delineate the future burden of breast cancer, we calculated population-based projections of breast cancer incidence through 2030.&amp;#x2028; Material and Methods: SEER data provided current age- and race-specific incidence rates for invasive or in situ female breast cancer. Age- and race-specific projections for the US population through 2030 were derived from Census Bureau data. Assuming stable race- and age-adjusted incidence, the total number of breast cancer cases by race and age through 2030 was estimated.&amp;#x2028; Results: From 2008 to 2030, the total number of breast cancer cases is expected to increase from 264,000 to 357,000. Of cases diagnosed in 2030, 60% will occur in women ages 65 and older. This represents a 67% increase in the number of breast cancer cases in women age 65 and over (from 127,000 to 212,000), compared to a 6% increase in women under age 65 (from 137,000 to 145,000). In 2030, 19% of all cases will occur in non-whites, representing a 70% increase in non-whites (from 40,000 to 68,000), compared to a 29% increase in whites (from 224,000 to 289,000). While cases in older non-white women currently represent only 13% of older patients, they will comprise 17% by 2030.&amp;#x2028; Discussion: With major demographic shifts on the horizon, an imminent wave of older breast cancer patients will impose a substantial burden on the US healthcare system. Efforts to expand capacity, contain cost, and define optimal treatment for older patients are urgently needed. Moreover, the projected increase in the percentage of breast cancer in non-whites heightens the importance of efforts to identify and minimize health care disparities.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6076.
Abstract 3402: Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF mutant thyroid carcinomas.
Authors: Cristina Montero-Conde, Sergio Ruiz-Llorente, Jose M. Dominguez, Jeffrey A. Knauf, Agnes Viale, Eric J. Sherman, Mabel Ryder, Ronald A. Ghossein, Neal Rosen, James A. Fagin
Journal: Cancer Research (2013)

Abstract The RAF inhibitor vemurafenib (PLX4032) increases survival in patients with BRAF-mutant metastatic melanoma, but has limited efficacy in patients with colorectal cancers. A trial with vemurafenib for thyroid cancer patients is now in progress. We compared the response of thyroid and melanoma cell lines harboring BRAFV600E to vemurafenib and found that the majority of thyroid cancer cells were refractory to the inhibitor (IC50 &amp;gt; 1.5 μM). In addition, thyroid cancer cell lines showed a rebound in pERK beginning 6h post-treatment and a transient activation of pAKT. Expression profiling and pRTK array screens of PLX4032-treated cells showed higher expression and activation of HER family receptors, particularly HER2 and HER3. Phosphorylation of HER3 represented the most consistent PLX4032-dependent RTK activated across thyroid cancer cell lines (5/6 lines tested) and was not detectable in any of the melanoma or colorectal cancer cells we investigated. HER3 phosphorylation was also induced by the allosteric MEK inhibitor PD0325901 in thyroid cancers of TPO-Cre/LSL-BrafV600E mice. We identified HER2 as the main HER3 heterodimerization partner, which was activated via a neuregulin-dependent autocrine loop, which was specific to the thyroid cancer lineage, as it was not observed in either melanoma or colorectal BRAF-mutant lines. HER3 transcription was induced by MAPK inhibition, via dissociation of the CTBP1/2 transcriptional repressors from the HER3 gene promoter. Finally, the HER2/HER3 kinase inhibitor lapatinib sensitized BRAF-mutant thyroid cancer cells to growth inhibition by RAF or MEK inhibitors in vitro and in vivo, providing rationale for combination therapies in this disease. Hence, the early response of BRAF-mutant cancers to selective MAPK pathway inhibitors is marked by the relaxation of oncoprotein-driven negative feedback events, which differ between tumors of various lineages, and which predict a requirement for distinct therapeutic strategies. Citation Format: Cristina Montero-Conde, Sergio Ruiz-Llorente, Jose M. Dominguez, Jeffrey A. Knauf, Agnes Viale, Eric J. Sherman, Mabel Ryder, Ronald A. Ghossein, Neal Rosen, James A. Fagin. Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF mutant thyroid carcinomas. [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 3402. doi:10.1158/1538-7445.AM2013-3402
Imaging the Brain
Authors: Sid Gilman
Journal: New England Journal of Medicine (1998)

Exciting advances in anatomical imaging have greatly improved our capacity to detect pathologic processes in the nervous system, localize these processes precisely, and predict the type of disease more accurately than ever before (Table 1). These advances, coupled with new and emerging therapies for previously untreatable diseases, have expedited the evaluation of patients with neurologic disorders and permitted the rapid initiation of therapy. In acute ischemic stroke, for example, brain imaging is required before the administration of recombinant tissue plasminogen activator, and treatment within three hours of onset greatly improves the outcome.1 The rapid evolution of techniques of anatomical imaging . . .
The Increased Needs of Patients in Nursing Homes and Patients Receiving Home Health Care
Authors: P W Shaughnessy, A M Kramer
Journal: New England Journal of Medicine (1990)

To evaluate the effects of Medicare's prospective payment system and Medicaid's preadmission regulations on long-term care, we constructed clinical profiles in 1982 and 1986 of about 500 randomly selected patients from each of three types of facilities: nursing homes with relatively high proportions of Medicare patients (high-Medicare nursing homes; n = 23), traditional nursing homes (n = 19), and home health agencies (n = 18). Data were obtained directly from the care givers on the medical problems, problems requiring skilled nursing, and functional problems of these representative patients from 12 states. For Medicare patients in high-Medicare nursing homes, the prevalence of medical problems and problems requiring skilled nursing increased substantially, whereas the prevalence of functional problems remained relatively unchanged. For example, from 1982 to 1986 there was a marked increase in the frequency of tube feedings (21 to 29 percent), oxygen use (6 to 14 percent), urinary tract infection (7 to 13 percent), and diastolic hypertension (1 to 10 percent), but not difficulty in eating (48 to 51 percent) or speaking (28 to 29 percent). In contrast, in traditional nursing homes there was an increase in the prevalence of functional disability, but virtually no change in that of problems requiring medical and skilled nursing care. In home health care the functional care needs of Medicare patients increased significantly, and there was a slight increase in the prevalence of problems requiring medical and skilled nursing care. We conclude that from 1982 to 1986 the needs of patients in long-term care increased substantially. This trend appears to result from Medicare's prospective payment system, which encourages earlier hospital discharge to long-term care settings, and from Medicaid's policy of de-institutionalization. Meeting this greater need for care will be costly. We require a better system of reimbursing for long-term care and ensuring its quality.
A Phase II Study On 3RD-Line Chemotherapy Combined Bevacizumab with S-1 for Colorectal Cancer with Mutated KRAS
Authors: Y. Miyake, A. Takagane, K. Shimada, N. Nagata, A. Sato, Y. Ogata, M. Fukunaga, K. Otsuka, Y. Matsubara, M. Yoshida
Journal: Annals of Oncology (2013)
HIS BUNDLE PACING TO BYPASS LEFT BUNDLE BRANCH BLOCK: THE RELATIONSHIP BETWEEN PRE-PACING QRS AXIS AND PACING-INDUCED QRS NORMALIZATION
Authors: Alexandra Teng, Daniel Lustgarten, Pugazhendhi Vijayaraman, Gopi Dandamudi, Kalyanam Shivkumar, Roderick Tung, Galen Wagner, Olujimi Ajijola
Journal: Journal of the American College of Cardiology (2016)