tbuckley/cabot-search huggingface dataset:
THU0074 Association between Disease Activity, Inflammation on MRI and Bone Loss in Early Axial Spondyloarthritis. Cluster Analysis
Authors: E. Gubar, A. Bochkova, A. Smirnov, E. Tukchova, T. Dubinina, A. Demina, O. Rumyantseva, S. Shubin, S. Gluhova, S. Erdes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To study the association between disease activity (BASDAI/ASDAS-CRP), MRI inflammation of sacroiliac joints (SIJs), lumbar spine (LS) and hip joints (HJs) and bone mineral density (BMD) in early axial spondyloarthritis (axSpA) patients. <h3>Methods</h3> 73 patients (33 men and 40 women) with early axSpa (according to ASAS criteria) were studied: disease duration – 19.9±14.4 months. Age –28.3±6.4 years, BASDAI – 4.1±1.9; ASDAS-CRP – 2.7±1.3. BMD was measured using dual energy x-ray absorptiometry (DXA) of femoral neck (FN) and LS (L2-4). BMD was evaluated according to Z-score. MRI of SIJs, LS and HJs (in case of hip joint involvement) was also performed using a scanner Signa Ovation 0.35 T (matrix 288x192). Inflammatory lesions (IL) on MRI (STIR) were evaluated by an independent reader. Cluster analysis was used for interpreting the results. <h3>Results</h3> Cluster analysis allowed to group two sets of related indicators. The first set contained the values of activity indices (BASDAI, ASDAS-CRP), as well as the BASFI functional index; the second group – the MRI-IL of SIJs, LS and HJs and the BMD results. Cluster analysis revealed correlation between the two groups (euclidean distance – 20). This indicates an association between the SpA activity indices (BASDAI, ASDAS-CRP) and the values of BMD in LS and FN, as well as inflammatory MRI changes in SIJs, LS and HJs (Fig. 1). Note the low correlation between the inflammation index and ESR and CRP. <h3>Conclusions</h3> Early axSpA patients have an association between the MRI inflammation of SIJs, LS and HJs and the BMD reduction in the nearby bone-joint system, their combination with BASDAI and ASDAS activity, and the lack of correlation with acute phase reactants (ESR, CRP). <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2807
INFORMATION-GUIDED SURGERY USING INTRAOPERATIVE MRI AND FUNCTIONAL MAPPING FOR GLIOMAS.
Authors: Y. Muragaki, H. Iseki, T. Maruyama, T. Suzuki, K. Yoshimitsu, M. Chernov, S. Ikuta, M. Tamura, J. Okamoto, M. Hayashi, Y. Okada
Journal: Neuro-Oncology (2014)

BACKGROUND: Contemporary technological developments revolutionized surgical management of intraaxial brain tumors. The intraoperative MRI (iMRI) and updated neuronavigation permitted for neurosurgeons to perform tumor resection under precise guidance. Neurophysiological monitoring and brain mapping allows precise localization of the cerebral functions and preservation of the important function during removal of the tumor. Intraoperative histopathological diagnosis allows fast direct investigation for identification of the neoplastic cells. Incorporation of these adjuncts provides for the surgeon an opportunity to perform aggressive glioma resection with minimal risk of neurological morbidity. The present report highlights our experience with information-guided surgical management of gliomas using low magnetic field strength iMRI in the intelligent operating theater with an emphasis on tumor resection rate and outcome. METHODS: From 2000 to 2013, 1234 surgeries for intracranial lesions were performed with the use of intraoperative MRI (iMRI) with low magnetic field strength of 0.3 Tesla, updated neuronavigation, serial intraoperative histopathological investigations, and neurophysiological monitoring (1000 gliomas, 45 cavernous malformations, 34 pituitary tumors, and other tumors). Newly-diagnostic gliomas followed more than one year were 533 cases (8 biopsies, 525 craniotomy) and WHO grade-II, -III, and -IV gliomas resected were 197, 150, and 170 cases, respectively (8 not specified). Adjuvant therapy for grade-II, -III, and IV patients was radiation (RT) and/or ACNU chemotherapy if resection rate were less than 90%, RT + ACNU, and RT + TMZ, respectively. RESULTS: Mean resection rates (RR) of grade-II, -III, and -IV were 87.7%, 89.5%, and 93.7%, respectively (P = 0.0004). Five-year and 10-year- survival rates of grade-II patients were 91.7% and 78.3%, those of grade-III patients were 76.9% and 71.9%, and 5-year survival of grade-IV patients were 19% (P = 0.042). RR of all-grade patients underwent awake craniotomy with functional mapping (AC: n = 174) and general anesthesia without functional mapping (GA: n = 351) were 86% and 93% (P < 0.001), and 5-year SR of AC and GA were 81.8% and 60.2% (P < 0.0001). However, RR of grade-II and -III patients underwent AC and GA were 85% and 92%, and 5-year SR of them were not significantly different (90% vs. 83%: P > 0.05). RR of patients with iMRI and without iMRI were significantly different in grade IV (94% vs. 78%: P < 0.0001) but not in grade II and III (89% vs. 87%: P > 0.05)). Overall survival of Grade-IV patients with iMRI and without MRI were 21 months and 11 months (P = 0.037). CONCLUSIONS: Information-guided management of gliomas using functional mapping and low-field-strength iMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage. SECONDARY CATEGORY: Imaging.
Abstract 3437: P276, a cyclin-dependent kinase inhibitor with antitumor activity against high-risk human cervical cancer.
Authors: Sanjeev Kumar Shangary, Gandhali Deshpande, Vinay Sonawane, Venkatesha Venkatasubbaiah, Archana Jalota-Badhwar, Asavari Joshi, Manoj Mayekar, Nitesh Shirsath, Prashant Pandey, Veena R. Agarwal
Journal: Cancer Research (2013)

Abstract Cervical cancer is the third most common cancer worldwide in women. While preventive vaccines have been approved for cervical cancer, treatment options are limited to chemotherapy drugs. An unmet need, thus, exists for the treatment of cervical cancer. High-risk human papilloma viruses (HPVs), type 16 and 18, account for 70% of the cervical cancer. Viral oncoproteins E6 and E7 bind and inhibit the p53 and Rb tumor suppressors, respectively. One attractive strategy for the treatment of cervical cancer is to attenuate the expression of E6 and E7 viral oncoproteins by a pharmacological inhibitor of cyclin-dependent kinases (CDKs). P276 is a CDKs inhibitor with potent activity against CDK4, CDK1 and CDK9 (Joshi et al, Mol. Cancer Ther. 2007; 6:918-25). The therapeutic potential and mechanism of action of P276 in cervical cancer was investigated using high-risk HPV type 16 (SiHa and Caski) and type 18 (HeLa) human cervical cancer cell line. P276 inhibited cell growth with sub-micromolar IC50 values (0.5-0.8 μM), induced cell cycle arrest and apoptosis in cervical cancer lines. E6 negatively regulates p53 protein stability in HPV-infected cervical cancer. P276 downregulated mRNA and protein expression of E6 in SiHa cells with concomitant upregulation of p53 protein and its downstream target p21, indicating activation of the p53 pathway. It also downregulated E7 mRNA expression in SiHa and HeLa cell lines. Further, it is known that hyperphosphorylation of Rb relieves its interaction with E2F, leading to Rb inactivation and E2F activation. Treatment with P276 dephosphorylated Rb at Ser780, indicating Rb activation. P276 demonstrated significant (p&amp;lt;0.01) in vivo efficacy in HPV type 16 SiHa human cervical cancer xenograft model when administered by i.p. route, Treatment with 25 mg/kg of P276 for 21 days induced 59% of tumor growth inhibition without body weight loss in this model. Conclusion: P276, a CDKs inhibitor, is efficacious against high-risk cervical cancer. Citation Format: Sanjeev Kumar Shangary, Gandhali Deshpande, Vinay Sonawane, Venkatesha Venkatasubbaiah, Archana Jalota-Badhwar, Asavari Joshi, Manoj Mayekar, Nitesh Shirsath, Prashant Pandey, Veena R. Agarwal. P276, a cyclin-dependent kinase inhibitor with antitumor activity against high-risk human cervical cancer. [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 3437. doi:10.1158/1538-7445.AM2013-3437
First report of MYD88L265P somatic mutation in IgM-associated light-chain amyloidosis
Authors: Rajshekhar Chakraborty, Anne J. Novak, Stephen M. Ansell, Eli Muchtar, Prashant Kapoor, Suzanne R. Hayman, Angela Dispenzieri, Francis K. Buadi, Martha Q. Lacy, Rebecca L. King, Morie A. Gertz
Journal: Blood (2016)
ALCOHOL WITHDRAWAL RECOGNITION, SCREENING AND PRESCRIPTION PRACTICES IN THE ACUTE MEDICAL SETTING
Authors: N Moran, E Jones, A O'Toole, S Patchett, G Harewood, F Murray
Journal: Gut (2013)

<h3>Introduction</h3> Delirium tremens (DT) is defined by hallucinations, tachycardia, hypertension, fever, agitation, and diaphoresis in the setting of acute reduction or abstinence from alcohol. DT is a medical emergency associated with a 5% mortality rate. There are established hospital guidelines available to guide the management of alcohol withdrawal and validated screening tools available to assess and treat patients. <h3>Aims/Background</h3> To assess practices surrounding alcohol withdrawal screening and appropriate prescribing in acute medical admissions in a University Hospital. <h3>Method</h3> In the emergency department, we obtained details of all non-elective admissions during one week from 6th-10th February 2013. We reviewed admission notes to classify patients according to risk of alcohol withdrawal. We recorded whether alcohol consumption was recorded, if screening tools to assess for withdrawal risk were used, if withdrawal was managed appropriately and if the alcohol liaison nurse was consulted. In addition we noted if refeeding syndrome risk was monitored. <h3>Results</h3> 110 patients were included; 57 female (52%) and 53 male (48%). Median age was 67 (range 19–88 years). 82.5 % had alcohol consumption documented. Of these 67.5 % were expressed in units per week. 8% (n=6) were identified as being at risk of alcohol withdrawal, of these 50 % were treated with IV Thiamine and Chlordiazepoxide. 33% (2/6) were referred to the alcohol liaison services. 1 patient had routine electrolyte measurement. No patients developed DT. <h3>Conclusion</h3> 8% of all patients were at risk of alcohol withdrawal. The appropriate management and alcohol liaison referral was prescribed in less than 50%.
SAT0388 Comparative assessment of methotrexate and leflunomide by magnetic resonance imaging in patients with early rheumatoid arthritis:
Authors: M.P. Lisbona, J. Maymό, A. Solano, M. Almirall, S. Sanchez, A. Pamies, M. Navallas, J. Carbonell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the efficacy comparing methotrexate and leflunomide by hand magnetic resonance imaging (h-MRI) in early RA patients. <h3>Methods</h3> A prospective cohort of patients with early RA (duration of symptoms &lt;1 year), naïve to DMARD or biologic therapy, were randomly assigned to receive either methotrexate (MTX) and leflunomide (LF) treatment (1:1 ratio). Forty-one patients assigned to the MTX group received an initial dose of 12.5 mg/week that was increased to 20-25 mg if persistent clinical activity and 37 patients were randomized to receive leflunomide 20 mg/day. Low-dose of glucocorticoids and NSAID was allowed and doses were stable during the study period. 1.5T MRI of the dominant hand, clinical assessment, disability (HAQ) and laboratory analyses were obtained before starting treatment and 16 weeks after. MR images were read blind for clinical results and treatment group, without knowing chronological order by 2 experienced readers (MPL, AS) following RAMRIS recommendations. Tenosynovitis was also scored. Data evaluation and statistical analysis were performed using SPSS v.15. <h3>Results</h3> A total of 78 RA patients were included, of these 62 pacients had paired h-MRI (33 with MTX and 29 with LF). Sixteen patients withdrew treatment (6 patients moved residence, 6 declined to participate, 3 loss of compliance of treatment and 1 case of pregnancy desire). No patients showed inefficacy or adverse events. Baseline characteristics including MRI parameters were similar (no significantly different) between the 2 treatment groups. Significant improvement in all activity measures, HAQ and RAMRIS synovitis were observed in the LF- and MTX-treated patients after 16 weeks of therapy. MTX group showed significant reduction of tenosynovitis score. No statistically significant differences between 2 treatments were observed, except that the SDAI reduction was greater in the MTX group (table 1). <h3>Conclusions</h3> Methotrexate and leflunomide showed comparable clinical efficacy and reduction on MRI synovitis at week 16 without significant differences between the both active treatments. <h3>Disclosure of Interest</h3> None Declared
Abstract 5371: A pooled apoptome shRNA screen to identify pathways that enhance NVP-BEZ235-induced apoptosis
Authors: Elisabeth Buchdunger, Andreas Theuer, Malika Kazic, Marc Hattenberger, Daniel Guthy, Johannes Roesel, Saskia Brachmann, Sauveur-Michel Maira
Journal: Cancer Research (2011)

Abstract NVP-BEZ235 is a dual inhibitor of class 1 phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) catalytic activity. It induces cell death in a subset of breast cancer cell lines characterized by amplification of human epidermal growth factor receptor 2 (HER2/ErbB2) and/or activating PIK3CA mutations, but not in cell lines with loss of function of the PTEN tumor suppressor protein or KRAS mutations. In order to better understand the molecular mechanisms leading to cell death, to identify potential biomarkers of activity and to reveal pathways that may even enhance NVP-BEZ235 induced lethality, a pooled short hairpin RNA (shRNA) screen using a lentiviral-based shRNA library targeting the apoptome was performed in NVP-BEZ235-sensitive MDA-MB453 and HCC1954 breast cancer cells. This strategy led to the identification of shRNAs that sensitized cells to NVP-BEZ235-induced apoptosis. Top sensitizers included pro-survival BCL2 family members, BCL2L1 and MCL1. Validation studies were carried out with single shRNAs targeting BCL2L1 and MCL1 as well as drug combination studies of NVP-BEZ235 with ABT-263 or ABT-747, both BCL2 homology domain 3 (BH3)-only protein mimetics. Cell death assays and biochemical readouts including PARP cleavage support the use of BCL2 family inhibitors to enhance NVP-BEZ235-induced cell death in HER2 amplified/PIK3CA mutated breast cancer cells. 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 5371. doi:10.1158/1538-7445.AM2011-5371
A CROSS-SECTIONAL STUDY INVESTIGATING THE ASSOCIATION BETWEEN LIPOPROTEIN(A) CHOLESTEROL CONCENTRATION, HIGH DENSITY LIPOPROTEIN CHOLESTEROL CONCENTRATION, AND TRIGLYCERIDES: THE VERY LARGE DATABASE OF LIPIDS - 22 (VLDL-22) STUDY
Authors: Hussein Rahim, Renato Quispe, Krishnaji Kulkarni, Parag Joshi, Seth Martin, Steven Jones
Journal: Journal of the American College of Cardiology (2016)
Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Patients with Severe Hypercholesterolemia.
Authors: Khera Av, Won Hh, Peloso Gm, Lawson Ks, Bartz Tm, Deng X, van Leeuwen Em, Natarajan P, Emdin Ca, Bick Ag, Morrison Ac, Brody Ja, Gupta N, Nomura A, Kessler T, Duga S, Bis Jc, van Duijn Cm, Cupples La, Psaty B, Rader Dj, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins H, Lander E, Wilson Jg, Correa A, Boerwinkle E, Merlini Pa, Ardissino D, Saleheen D, Gabriel S, Kathiresan S
Journal: Journal of the American College of Cardiology (2016)
Drug points: Hypoglycaemia associated with formestane treatment
Authors: E Brankin, A Gallagher, M Soukop
Journal: BMJ (1997)

Objective: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure.Design: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts.Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults.Main outcome measures: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life.Results: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes.Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke.Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive.Only one small randomised controlled trial evaluated continuous positive airways pressure.Five non-randomised controlled trials and 38 uncontrolled trials were identified.Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed.Conclusions: The relevance of sleep apnoea to public health has been exaggerated.The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated.There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.
PTH-105 The Effect of Infliximab Pre-Treated Human Blood-Enriched Dendritic Cells from Patients with Active Crohn’S Disease and Healthy Controls on Subsequent Human T-Lymphocyte Phenotype and Cytokine Production in Vitro
Authors: S T C Peake, D Bernardo, E Mann, J Landy, H Omar, S C Knight, A L Hart
Journal: Gut (2013)

<h3>Introduction</h3> Dendritic cells (DC) play a key role in discriminating between commensal microorganisms and potentially harmful pathogens. Expression of surface markers and cytokine production by DC at the time of antigen presentation control T-cell differentiation, cytokine profile &amp; homing properties imprinted on stimulated T-cells. This process defines the type of immune response that occurs and its anatomical location. In CD, dysregulation of the immune response to gut microbiota and aberrant immune cell trafficking play a central role in disease pathogenesis. Infliximab (IFX) is an effective treatment for CD, but its mechanism of action is unclear. In this study, we investigated the effect of IFX pre-treated blood-enriched DC, isolated from patients with active CD and healthy controls (HC), on human T-cell proliferation, phenotype&amp;cytokine production <h3>Methods</h3> Low density cells (LDC), enriched for DC, were obtained following Ficoll and Nycoprep gradient separation of fresh blood from patients with active ileocolonic CD (CDAI &gt; 220) and HC. LDC were cultured (0.5x106cells/ml) with IFX (1.10μg&amp;100μg/ml&amp;basal) for 24hr. T-cells were enriched from allogeneic HC blood and labelled with CFSE. LDC were added to T-cells in complete medium (400,000cells/ml) at basal,1.2&amp;3% concentrations and incubated for 5days. Following incubation, T-cell proliferation, expression of β7&amp;CLA surface homing markers and cytokine content of T-cells (TNFα, TGFβ, IFNγ, IL-10.15.17) was quantified by flow cytometry on stimulated T-cells. Unparied t-test and one-way ANOVA statistical analyses were applied <h3>Results</h3> In basal conditions, LDC from HC &amp; CD patients did not differ in their stimulatory capacity for allogeneic T-cells or in the cytokine profile acquired by T-cells. However, T-cells stimulated by LDC from CD patients decreased β7 intensity ratio. Following culture with IFX, LDC decreased their stimulatory capacity in a dose-dependent, stepwise fashion in both HC and CD. Culture with IFX did not have any effect on the acquired homing profile of stimulated T-cells, although these T-cells had a trend (not statistically significant) towards lower TNFα and higher IL-17 production <h3>Conclusion</h3> The marked reduction in the ability of LDC to stimulate T-cells following culture with IFX represents one plausible explanation for the efficacy of anti TNF-alpha therapies in the treatment of CD. This effect was dose-dependent (within our range of test concentrations) suggesting that higher doses of IFX further reduce T-cell stimulation and may provide one explanation of the clinical benefits of dose escalation in refractory CD <h3>Disclosure of Interest</h3> None Declared.
Meeting Report: Agricultural Chemical Utilization and Human Health
Authors: Elizabeth W. Mushak, Warren T. Piver
Journal: Environmental Health Perspectives (1992)

The public is justifiably concerned about the human health effects of agricultural chemicals. The many gaps in information about the mechanisms of toxic action, human exposures, and the nature and extent of human health effects are large. Very few older pesticides, in particular, have been tested for human health effects. Workers who produce, harvest, store, transport, process, and prepare food and fibers are exposed to many chemicals that are potentially hazardous and that are used in agriculture. The occupational health of these workers has not been adequately studied, and protective efforts have sometimes been minimal. Valid and accurate risk assessment is best based on sound information about how chemicals, in this case agricultural chemicals, are involved in toxic events-their mechanisms of action. These health effects include tumor promotion, chronic and acute neurotoxicity, immunotoxicity, and reproductive and developmental toxicity. Another key part of risk assessment is exposure assessment. Fundamental studies of the toxicology of target organisms and nontarget organisms exposed to agricultural chemicals are needed to discover and develop better solutions to the problems of agricultural pest control, including better formulations, optimal application rates and public education in safety and alternative agricultural practices. The large number of pesticides that have never been adequately tested for effects on human health is particularly worrisome in light of emerging information about delayed nervous system effects.
More adenomas – less cancer? Advanced imaging in colonoscopy
Authors: Michael Bretthauer, Peter Siersema
Journal: Endoscopy (2015)

High quality colonoscopy is a prerequisite for effective colorectal cancer (CRC) screening programs. During recent years, a lot of emphasis has been put on improvement of colonoscopy quality to increase the quality of screening programs. A number of key quality indicators have been proposed for colonoscopy. These include the quality of bowel preparation, cecum intubation rate, withdrawal time, completeness of polyp removal, patient safety and satisfaction, and adenoma detection rate (ADR).
Frost and fogs, or sunny skies? Orthography, reading, and misplaced optimalism
Authors: David L Share
Journal: Behavioral and Brain Sciences (2012)

Abstract I argue that the study of variability rather than invariance should head the reading research agenda, and that strong claims of orthographic “optimality” are unwarranted. I also expand briefly on Frost's assertion that an efficient orthography must represent sound and meaning, by considering writing systems as dual-purpose devices that must provide decipherability for novice readers and automatizability for the expert.