tbuckley/cabot-search huggingface dataset:
S52 Is A Raised Bicarbonate, Without Hypercapnia, Part Of The Physiological Spectrum Of Obesity-related Hypoventilation?
Authors: A. Manuel, N. Hart, J. Stradling
Journal: Thorax (2014)

<h3>Introduction</h3> Obesity Hypoventilation Syndrome (OHS) is conventionally defined by the combination of obesity (BMI &gt;30 kg/m<sup>2</sup>) and daytime hypercapnia (PaCO<sub>2</sub> &gt;6 kPa, with no other explanation) and sleep-disordered breathing may or may not be included. OHS patients have a higher morbidity, mortality, and health care utilisation compared with non-hypercapnic obese subjects. We hypothesised that in obese patients, even in the absence of a raised daytime PaCO<sub>2</sub>, the presence of a raised plasma standard bicarbonate, or base excess (BE, as a biomarker of whole body acid-base balance) would be associated with some well-recognised features of OHS (reduced ventilatory drives to hypoxia and hypercapnia, and nocturnal hypoventilation), thus suggesting they represent ‘early’ OHS. <h3>Methods</h3> Obese subjects (BMI &gt;30 kgs/m<sup>2</sup>) were identified from a variety of sources, and divided into those with: 1) normal arterial blood gases and normal acid-base balance, 2) an isolated raised arterial BE (≥2 mmol/L), and 3) awake arterial hypercapnia (&gt;6 kPa, i.e. established OHS). Two-point ventilatory responses to hypoxia (15 min poikilocapnic response to 15% O<sub>2</sub>) and hypercapnia (15 min response to 5%CO<sub>2</sub> in O<sub>2</sub>) were performed. Derivatives included the fall in SaO<sub>2</sub> and rise in end-tidal CO<sub>2</sub> when stable, and conventional ventilatory drive calculations. Polygraphic sleep studies were done with the derivatives of intermittent (oxygen desaturation index) and prolonged hypoxia (time below 90% SaO<sub>2</sub>) reported here. <h3>Results</h3> 71 subjects (BMI 47.2, SD 9.8; age 52.1, SD 8.8) were recruited into the above three groups (33, 22, and 16 respectively). The table shows the BMI, PaCO<sub>2</sub> and BE for the three groups, along with the selected derivatives of the ventilatory drive measurements and sleep studies. For nearly all the ventilatory response and sleep study derivatives, group 2 (with only an isolated raised BE) represented a middling group, and for some of the measures this middle group was more similar to group 3, with established OHS, rather than group 1. <h3>Conclusion</h3> This study shows that obese individuals with raised BE, but without awake hypercapnia, probably represent an intermediary stage towards overt obesity-hypoventilation syndrome. Further studies will be required to establish if early intervention for this group is beneficial.
A New Era in Secondary Prevention after Acute Coronary Syndrome
Authors: Matthew T. Roe, E. Magnus Ohman
Journal: New England Journal of Medicine (2011)

During the past two decades, the use of antiplatelet therapies has been the focus of new studies of secondary prevention after acute coronary syndromes, with more than 75% of patients in contemporary practice treated with dual antiplatelet therapy (aspirin plus a thienopyridine) on hospital discharge.1 Despite increases in the use of antiplatelet therapies and the development of more potent antiplatelet therapies (prasugrel and ticagrelor), the residual risk of death, myocardial infarction, or stroke up to 1 year after acute coronary syndromes remains high2,3 (Table 1). This represents a therapeutic challenge, since the balance between risk (major bleeding) and benefit . . .
Endoscopic findings of small-intestinal Epstein-Barr virus-associated T-cell lymphoproliferative disorder
Authors: S. Sazuka, Y. Takahashi, T. Kawaguchi, T. Sato, T. Nakagawa, Y. Furuya, M. Saito, K. Saito, T. Katsuno, C. Nakaseko, O. Yokosuka
Journal: Endoscopy (2012)

A 71-year-old woman was admitted to our hospital in October 2009 with a 3-month history of severe diarrhea and weight loss of 5 kg with hypoalbuminemia. Computed tomography showed diffusely thickened small-intestinal wall and intra-abdominal lymphadenopathy. Capsule endoscopy revealed flattened villi throughout the small intestine ([Fig. 1]). Double-balloon enteroscopy confirmed diffusely atrophic small-intestinal villi and clearly visible Peyer's patches ([Fig. 2]). No neoplastic changes were observed on hematoxylin and eosin staining of the small-intestinal mucosa, but atrophic villous structures tentatively suggested celiac disease ([Fig. 3]). Although blood tests indicated positivity for anti-gliadin antibodies, celiac disease was excluded as the patient's symptoms were not alleviated by being on a gluten-free diet for 1 month.
P3-06-08: SCAN-B: An Accelerated Translational Pipeline from Profile to Prognosis and Prediction for Individual Breast Cancer Patients.
Authors: N Loman, LH Saal, J Häkkinen, J Vallon-Christersson, M Ringnér, C Hegardt, G Jönsson, SK Gruvberger-Saal, A Kvist, C Reuterswärd, R Schulz, A Karlsson, M Jönsson, D Grabau, J Manjer, J Carlson, J Malina, C Larsson, L Rydén, Å Borg
Journal: Cancer Research (2011)

Abstract The South Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative is a multidisciplinary network of clinical providers of breast cancer (BC) treatment and pre-clinical scientists whose multiyear purpose is to 1) prospectively collect and analyze the “-omes” of a very large, consecutive, and population-based sample of BCs for translational research; 2) utilize this genomic data to develop new clinically-relevant biomarker assays; and 3) to build the infrastructure for future real-time clinical implementation of resultant biomarkers for individualized treatment. Patient enrollment began in the Fall of 2010 at the seven BC surgical units of the South Sweden Healthcare Region, where approximately 1500 new breast cancer diagnoses are treated yearly following the guidelines of the South Sweden Breast Cancer Group. Currently, tumor and blood samples are being collected at the rate of 80–100 patients per month, which represents approximately 75% of the catchment population. SCAN-B will initially focus on tumor transcriptome analysis using mRNA-sequencing on Illumina HiSeq 2000 instruments, and in the future multimodal data generated from other genomic platforms will also be integrated. Here we present initial experiences from this multidisciplinary collaboration including descriptions of the clinical routines, specimen handling, laboratory processing, mRNA-seq data quality control, short- and long-term projects and future directions. We believe large initiatives like SCAN-B could significantly reduce the time to discovery, validation, and clinical implementation of more powerful diagnostic, prognostic, and treatment-predictive tests for breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-08.
People with poorer numeracy feel more negative about bowel cancer screening
Authors: Z. Kmietowicz
Journal: BMJ (2014)

People with low numeracy may be more likely to feel negative about bowel cancer screening, including fearing an abnormal result, new research has found.

For the study, published in the Journal of Health Psychology ,1 researchers sent information about bowel cancer screening to patients aged 45 to 59, along with a questionnaire that assessed their numerical skills and attitudes to screening.

Almost 965 people (of 4452; response rate 22%) from four GP practices in the north of England returned the questionnaire. Of these, nearly half (46%) replied incorrectly to …
Increasing the impact of health services research on service improvement: the researcher-in-residence model
Authors: Martin Marshall, Laura Eyre, Mirza Lalani, Salmaan Khan, Susan Mann, Debi de Silva, Jonathan Shapiro
Journal: Journal of the Royal Society of Medicine (2016)

Proponents of evidence-based medicine often quote the 17-year lag between the publication of clinical research and its impact on the behaviour of front line staff. Less attention has been shown to the lag in health services research (HSR) impacting on decisions made by managers or clinicians about the organisation and delivery of health services. Yet, HSR has greater potential to positively influence service delivery than is generally realised, and as health systems around the world struggle to improve quality while controlling costs, they are becoming more interested in organisational research evidence. In this paper, we describe a new approach to increasing the impact of research, the researcher-in-residence model, which is being developed in a number of UK locations. We explore the model’s background and origins, present examples of its use in a London academic health science network, highlight learning from this early work and consider the next steps in its development.
Abstract 3317: The roles of TMCC3 in breast cancer cells
Authors: Ya- Hui Wang, Alice L. Yu
Journal: Cancer Research (2012)

Abstract There is growing evidence showing that cancer stem cells are more likely to metastasize and are more frequently detected in the circulation. Thus, it will be important to understand the molecular characteristics of breast cancer stem cells (BCSCs) which may lead to the development of novel targets for CSC-directed therapy. Through phosphoproteomic analysis of BCSC and non-BCSC, we identified differential expression of the transmembrane and coiled-coil domain family 3 (TMCC3). TMCC3 belongs to TEX28 family and is predicted to be an integral membrane protein. The function of TMCC3 is unknown. We found higher expression of TMCC3 in invasive breast cancer cell line and BCSCs than less-invasive breast cancer cell lines, and non-BCSCs, respectively. In addition, TMCC3 expression was greater in distant lymph node metastasis than in primary tumor of human breast cancer xenograft in mouse. Silencing of TMCC3 led to G1 phase arrest with increased apoptotic cells, along with decreased mammosphere formation and ALDH activity which are important features of cancer stem cell. In our previous investigation, the IGF-1R/PI3K/Akt/mTOR pathway was shown to be important for BCSCs survival and maintenance. To explore the possible involvement of TMCC3 in this pathway, we further examined the Akt and mTOR activation in TMCC3-slienced BCSCs. We found the Akt phosphorylation was lost in BCSCs upon TMCC3 knocked down. These findings suggest that TMCC3 is essential for breast cancer cell survival, self-renewal and metastasis. Thus, inhibition of TMCC3 may provide a new therapeutic strategy targeting stem cells. 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 3317. doi:1538-7445.AM2012-3317
PLAQUE CHARACTERISTICS AND VASCULAR RESPONSE TO LIPID-LOWERING THERAPY IN PATIENTS WITH HIGH VERSUS LOW HDL-CHOLESTEROL: SERIAL OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND STUDY
Authors: Yoshiyasu Minami, Jingbo Hou, Haibo Jia, Sining Hu, Rocco Vergallo, Tsunenari Soeda, Shaosong Zhang, Bo Yu, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2015)
FRI0249 Case Definition for Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography (HR-PQCT): an International Spectra Reliability Exercise-1 (RELEX-1)
Authors: C. Barnabe, S. Kraus, H. Marotte, E.-M. Hauge, A. Scharmga, R. Kocijan, D. Töpfer, S. Boutroy, K.K. Keller, J. de Jong, J. Williams, K.S. Stok, S. Finzel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel imaging instrument for bony damage in rheumatoid arthritis (RA). <h3>Objectives</h3> Agreement on a case definition for pathologic erosions is required given the sensitivity of HR-pQCT for detecting cortical bone disruptions. The reliability of erosion detection and measurement between readers is crucial to evaluate with this new technology, as HR-pQCT is undergoing validation as an outcome measurement tool. <h3>Methods</h3> HR-pQCT images of the 2nd and 3rd metacarpophalangeal joints of RA patients and control subjects were used in an iterative process to achieve consensus on a case definition for erosions. This case definition was applied by 11 independent readers to score 58 joints. Each surface (radial, ulnar, palmar, and dorsal) of the proximal phalanx and metacarpal head were characterized for image quality, presence of cortical break as well as appearance of the respective cortical break (physiological or pathological). Moreover, the total amount of pathologic erosions per quadrant as well as their width and depth in two perpendicular muliplanar reformations were recorded. <h3>Results</h3> The case definition requires the presence of a cortical break extending over at least two slices and seen in 2 orthogonal views. The break must be non-linear in shape to differentiate from vascular channels penetrating the cortical surface, and have underlying trabecular bone loss. Inter-reader agreement for erosion detection was at 90.2%. Discrepant scoring was attributable to lower quality images with multiple bony pathologies overlapping each other. Erosion size ranged from 0.016 to 0.890 cm in maximal width (mean 0.184 cm) and 0.030 to 0.800 cm in maximal depth (mean 0.186 cm), with between 12.3 and 24.0% variability in measurement between readers. <h3>Conclusions</h3> We have devised a new case definition for erosions visualized with HR-pQCT imaging. Inter-reader reliability for erosion detection is good, yielding promise to use HR-pQCT as an outcome measurement tool for bony damage. Further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3360
AB0918 Auto-antibodies in patients with ankylosing spondylitis untreated with biologic therapy
Authors: W. Hamdi, M.M. Ghannouchi, L. Laadhar, S. Makni, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> AnkylosingSpondylitis (AS) is a chronic inflammatory disease belonging to the spondylarthropathy group without immunity marker. Presence of auto-antibodies was unusual and frequently induced by biologic treatment. <h3>Objectives</h3> to evaluate the frequency and clinical significance of anti nuclear antibodies, (ANA), anti-DNA, anti-ENA, rheumatoid factor (RF) and anti-keratin antibody (AKA) in patients with AS before any biologic therapy. <h3>Methods</h3> We have performed a cross sectional study of 100 patients who fulfilled the modified New York Criteria for AS. Screening for auto-antibodies was performed by indirect immunofluorescence (Hep2 cells for ANA, Chritidia luciliae for anti-DNA and rat oesophagus for AKA), by ELISA for anti-ENA and by Latex for RF. Statistical analysis was performed by X2 test and Student t test. Significance was accepted for p&lt;0.05. <h3>Results</h3> Eighty nine men and 11 women were recruited, their mean age was 37, 9±11.7 years. The mean disease duration was 12.3±9.7 years, the mean age at the onset of the disease was 26,6±10,2 years. Peripheral arthritis was found in 76 patients and extra articular clinical pattern was found in 24 patients (anterior uveitis in 18 cases). Among patients with AS, 24 patients have at least one autoantibody, 22 patients have ANA with level &lt;1/200 in all cases, anti-ENA were found in two patients, AKA in 6 patients and RF in 4 patients. No relation was found between presence of auto-antibodies and articular or extra-articular clinical pattern in patients with ankylosing spondylitis. <h3>Conclusions</h3> Auto-antibodies seem to be frequent in AS but their level was low in most of cases and seems to have no impact in clinical pattern. <h3>Disclosure of Interest</h3> None Declared
Comparison of the Pharmacokinetics of Octreotide Injected at Two Subcutaneous Sites
Authors: S. R. PATEL, L. K. KVOLS, D. A. PETERSON, D. T. GILBERTSON, C. G. MOERTEL, T. M. O'DORISIO
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Comparison of the Pharmacokinetics of Octreotide Injected at Two Subcutaneous Sites Get access S. R. PATEL, S. R. PATEL Search for other works by this author on: Oxford Academic PubMed Google Scholar L. K. KVOLS, L. K. KVOLS Search for other works by this author on: Oxford Academic PubMed Google Scholar D. A. PETERSON, D. A. PETERSON Search for other works by this author on: Oxford Academic PubMed Google Scholar D. T. GILBERTSON, D. T. GILBERTSON Search for other works by this author on: Oxford Academic PubMed Google Scholar C. G. MOERTEL, C. G. MOERTEL Search for other works by this author on: Oxford Academic PubMed Google Scholar T. M. O'DORISIO T. M. O'DORISIO * 1Department of Endocrinology, The Ohio State UniversityColumbus, OH 43210 *Correspondence to: T. M. O'Dorision, M.D., Department of Endocrinology, The Ohio State University, Doan Hall, Rm. N1123, 410 W. 10th Ave., Columbus, OH 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1926–1929, https://doi.org/10.1093/jnci/81.24.1926 Published: 20 December 1989
Abstract 93: Usefulness of DNA methylation analysis using gastric washes as a treatment marker for early gastric cancer
Authors: Yoshiyuki Watanabe, Yoshichika Ohishi, Tetsuya Hiraishi, Ritsuko Oikawa, Tadateru Maehata, Hiromu Suzuki, Minoru Toyota, Fumio Itoh
Journal: Cancer Research (2011)

Abstract Aim: Although minimal invasive treatment is widely accepted for early stage of gastric cancer, we still do not have any appropriate risk markers to detect residual neoplasia and some potential of recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia, and that methylation analysis of DNA recovered from gastric washes was used to detect gastric neoplasia (Gastroenterology 2009). Here, we hypothesized gastric washes also can determine whether gastric cancer (GCa) was removed curatively by endoscopic treatment or not. Our goal is to find and identify some candidate genes as a treatment marker using genome wide DNA methylation analysis and for early gastric cancer. Method: We studied MCAM (Methylated CpG Island Amplification Microarray) analysis using 12 gastric washes (each 6 before and after endoscopic treatment in same patients) and identified candidate genes for further studies. Two of them are MINT25 and Sox17 (SRY (sex determining region Y)-box 17). We examined the DNA methylation status of these two genes in a validation set consisting of 128 washes samples (Pre, 64: Post, 64) at early gastric cancers by quantitative bisulfite-pyrosequencing analysis. Results: These two genes showed significantly differential methylation between before and after treatment in GCa patient (MINT25, p&amp;lt;0.0001: Sox17, p&amp;lt;0.0001). Moreover, we could successfully identified the incomplete endoscopic mucosal resection case by Sox17 methylation status, and additional resection resulted in the proof of residual cancer and decrease of Sox17 methylation level in gastric wash. Conclusion: We have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. It is easy and useful for early detection of recurrence after endoscopic treatment in GCa patients. 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 93. doi:10.1158/1538-7445.AM2011-93
AT-04 * TARGETING Myc DRIVEN TRANSCRIPTIONAL OUTPUT IN ATYPICAL TERATOID RHABDOID TUMOR
Authors: I. Alimova, S. Venkataraman, A. Pierce, A. Greisinger, D. Birks, I. Balakrishnan, N. Foreman, R. Vibhakar
Journal: Neuro-Oncology (2015)

Atypical Teratoid Rhabdoid Tumor (ATRT) is a highly aggressive pediatric brain tumor with poor outcomes characterized by loss of the ATP dependent chromatin remodeling protein SMARCB1. We recently performed transcriptomic analysis and identified BMP signaling as an adverse prognostic marker in ATRT. We also identified EZH2 as a key epigenetic regulator in ATRT. To further evaluate ATRT biology we reexamined our patient derived transcriptomic data using bioinformatics tools. Using GSEA and Ingenuity network analysis we found that C-Myc driven transcriptional signatures are over represented in ATRT compared to normal brain. C-myc is overexpressed in ATRT patient samples and in tumor cell lines. These data are supported by previous studies that suggest Myc transcription is suppressed by SMARCB1. Genetic inhibition of C-myc potently suppresses ATRT cell growth in vitro. Importantly inhibition of C-myc strongly attenuates ATRT cell self-renewal and promotes senescence by activating cell cycle checkpoint inhibitors. We next tested a new small molecule inhibitor of Myc activity, JQ1. JQ1 inhibits BRD4 activity and thus suppresses Myc driven signaling. We show that JQ1 suppresses ATRT cell growth in vitro and decreases proliferation as measured by BrdU incorporation. JQ1 also inhibited C-myc activity as measured by luciferase reporter assays. Further JQ1 strongly suppressed the ability of ATRT cells to migrate and invade in vitro. In vivo JQ1 slowed growth of intracranial orthotopic ATRT tumors compared to DMSO control treated animals. Tumor weights were significantly smaller at necropsy in JQ1 treated animals. Most importantly JQ1 significantly increased the latency of ATRT tumor formation in vivo in a minimal residual disease model of ATRT. These data highlight the importance of c-Myc driven transcription in ATRT and provide rationale for therapeutically targeting ATRT with BET inhibitors.
A pilot study evaluating a new low-volume colon cleansing procedure for capsule colonoscopy
Authors: D. Hartmann, M. Keuchel, M. Philipper, I. Gralnek, R. Jakobs, F. Hagenmüller, H. Neuhaus, J. Riemann
Journal: Endoscopy (2012)

<b>Background and study aims:</b> Colon capsule endoscopy (CCE) offers an alternative approach for endoscopic visualization of the colon. Some of the current CCE bowel cleansing regimens use sodium phosphate, which has raised safety concerns. Therefore, the aim of the current study was to test the feasibility and efficacy of a new low-volume, sodium phosphate-free polyethylene glycol (PEG) bowel preparation. <b>Methods:</b> The first 26 patients (original cleansing procedure) received a colon cleansing regimen of PEG plus ascorbic acid: patients drank 1 L in the evening and 0.75 L in the morning before capsule ingestion. Patients also drank an additional 0.5 L PEG boost and an optional 0.25 L PEG boost during the capsule procedure. Following an interim analysis, the cleansing procedure of the subsequent 24 patients was modified, with the morning intake before capsule ingestion being increased to 1 L, as well as the second boost (0.25 L) being administered 1 – 2 hours earlier (modified cleansing procedure). <b>Results: </b>The overall colon cleanliness was considered to be good or excellent in 83 % (original cleansing procedure) and 82 % (modified cleansing procedure) of patients, without any significant difference between regimens (<i>P</i> > 0.05). In 37 /49 (76 %) of the CCE procedures, the hemorrhoidal plexus was identified and thus the examination was considered complete, with no significant differences between the two CCE cleansing procedures. The capsule sensitivity and specificity for detecting colonic polyps ≥ 6 mm were 91 % (95 %CI 70 % – 98 %) and 94 % (95 %CI 87 % – 97 %), respectively, compared with standard optical colonoscopy. <b>Conclusion:</b> A colon cleansing procedure using PEG + ascorbic acid for capsule colonoscopy yielded an adequate cleansing level in > 80 % of patients, a completion rate of 76 %, and good accuracy for detecting polyps. This procedure may be considered as an alternative, particularly for patients in whom sodium phosphate-based preparations are contraindicated.