tbuckley/cabot-search huggingface dataset:
<i>GPIHBP1</i> Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding
Authors: Anne P. Beigneux, Loren G. Fong, André Bensadoun, Brandon S.J. Davies, Monika Oberer, Henrik Gårdsvoll, Michael Ploug, Stephen G. Young
Journal: Circulation Research (2014)

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia.We sought to understand mechanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia.We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and Drosophila S2 cells. In each expression system, mutation of cysteines in GPIHBP1's Ly6 domain (including mutants identified in patients with chylomicronemia) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization/multimerization was not unique to cysteine mutations; mutations in other amino acid residues, including several associated with chylomicronemia, also led to protein dimerization/multimerization. The loss of GPIHBP1 monomers is relevant to the pathogenesis of chylomicronemia because only GPIHBP1 monomers-and not dimers or multimers-are capable of binding LPL. One GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding-and often did so without promoting the formation of dimers and multimers.Many amino acid substitutions in GPIHBP1's Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization. Dimerization/multimerization is relevant to disease pathogenesis, given that only GPIHBP1 monomers are capable of binding LPL.
Violence in the workplace The nurse's experience Commentary: Could guidelines reduce number of incidents? Commentary: Carers deserve care too Commentary: Roles and identities
Authors: P. Gough, R. M Goss, S. Jordan
Journal: BMJ (2001)

# Violence in the workplace {#article-title-2}

In the following personal view, a nurse practitioner describes her experience of being assaulted during the course of her work. We invited a nurse, a patient, and a lecturer from a school of health science to comment.

# The nurse's experience {#article-title-3}

It began as real life drama always unfolds. A routine call, a routine night. This one had barely begun when I was called to review an agitated patient who was trying to leave the ward.

The patient, a tall, well built 46 year old man had been admitted with diabetic ketoacidosis to a busy medical ward the previous day. He had now decided he wanted a drink and a cigarette. Despite their best efforts, the three nurses on duty had been unable to persuade him to stay. I could hear his bellowing long before I reached the ward. He targeted me the moment I arrived. With clenched fists held in front of him he pushed me out of his way, hurling abuse at me as he left the ward. Medically he was unfit to be discharged so the police were called. They found him quickly and returned him to the ward. The minute he walked back on to the ward the verbal abuse started again. As they were concerned the police agreed to stay while I spoke to him. With a policeman on either side of him in case he tried to lash out I approached him.

What happened next shocked all that witnessed it. He couldn't reach me with his fists so he kicked me in the stomach with such force that I was sent reeling to the floor. For the first few seconds I felt completely numb, then I felt the sharp, stabbing pain in my abdomen. Tears were streaming down my face, everyone came to my aid, but I couldn't …
Management of Behcet disease: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for the management of Behcet disease
Authors: G Hatemi, A Silman, D Bang, B Bodaghi, A M Chamberlain, A Gul, M H Houman, I Kotter, I Olivieri, C Salvarani, P P Sfikakis, A Siva, M R Stanford, N Stubiger, S Yurdakul, H Yazici
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD. <h3>Methods:</h3> Problem areas and related keywords regarding the management of BD were determined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A systematic literature research was performed using MedLine and Cochrane Library resources through to December 2006. Meta-analyses, systematic reviews, randomised controlled trials (RCTs), open studies, observational studies, case control studies and case series' involving ⩾5 patients were included. For each intervention the effect size and number needed to treat were calculated for efficacy. Odds ratios and numbers needed to harm were calculated for safety issues of different treatment modalities where possible. <h3>Results:</h3> The literature research yielded 137 articles that met the inclusion criteria; 20 of these were RCTs. There was good evidence supporting the use of azathioprine and ciclosporin A in eye involvement and interferon (IFN)α in mucocutaneous involvement. There were no RCTs with IFNα or tumour necrosis factor (TNF)α antagonists in eye involvement. Similarly controlled data for the management of vascular, gastrointestinal and neurological involvement is lacking. <h3>Conclusion:</h3> Properly designed, controlled studies (new and confirmatory) are still needed to guide us in managing BD.
Clinical trials in rheumatoid arthritis: methodological suggestions for assessing radiographs arising from the GRISAR study
Authors: R Ferrara, F Priolo, M Cammisa, L Bacarini, A Cerase, G Pasero, G F Ferraccioli, O D. C. Alberighi, A Antonellini, E Marubini
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> The three <i>x</i> ray assessors of the GRISAR study (blinded to treatment) gave consensual erosion and damage scores to the baseline and 12 month radiographs of 284 rheumatoid arthritis (RA) patients using three different methods: single readings (blinded as to patient and chronological sequence of the <i>x</i> rays), paired readings (blinded as to sequence), and chronologically ordered paired readings. The aim was to evaluate which of these reading procedures is the most appropriate for clinical trials. <h3>METHODS</h3> The progression of the scores obtained using each procedure was compared by means of descriptive statistics, principal components analysis, and intra-patient correlation coefficients of pairs of methods. Bootstrap estimates of the variance of the difference in the means of two equally sized random samples were calculated to evaluate the power of the statistical analysis performed to assess the possible treatment effect for both paired and chronological reading methods. <h3>RESULTS</h3> (a)The standard deviations of the paired and chronological readings were similar, but that of the single readings was higher. (b) The knowledge that two <i>x</i> rays were of the same patient accounted for a sizeable proportion of the between method variability. (c) Agreement was satisfactory between the paired and chronological methods for both scores but, between them and the single readings, it was modest for erosions and poor for damage. (d) The bootstrap estimate of the variance of the difference was smaller for the paired than the chronological method, possibly giving it greater power to test treatment effect. <h3>CONCLUSIONS</h3> These results suggested that paired readings were the most suitable for evaluating the progression of joint damage in the GRISAR study.
Seeing Is Believing: Using Skype to Improve Diabetes Outcomes in Youth
Authors: Michael A. Harris, Kurt A. Freeman, Danny C. Duke
Journal: Diabetes Care (2015)

OBJECTIVE The objective of this study was to compare the relative effectiveness of two modes of delivering Behavioral Family Systems Therapy for Diabetes (BFST-D) to improve adherence and glycemic control among adolescents with type 1 diabetes with suboptimal glycemic control (HbA1c ≥9.0% [≥74.9 mmol/mol]): face to face in clinic (Clinic) and Internet videoconferencing (Skype) conditions. RESEARCH DESIGN AND METHODS Adolescents aged 12 to 18 years and at least one adult caregiver were randomized to receive BFST-D via the Clinic or Skype condition. Participants completed up to 10 therapy sessions within a 12-week period. Changes in youth- and parent-reported adherence and glycemic control were compared before and after the intervention and at follow-up assessment. RESULTS Using an intent-to-treat analytic approach, no significant between-group differences were identified between the before, after, and follow-up assessments. Groups were collapsed to examine the overall effects of BFST-D on adherence and glycemic control. Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after the intervention; improvements were maintained at 3-month follow-up. CONCLUSIONS Delivery of BFST-D via Internet-based videoconferencing is viable for addressing nonadherence and suboptimal glycemic control in adolescents with type 1 diabetes, potentially reducing important barriers to care for youth and families.
Structure and Expression of an Adhesive Protein–like Molecule of Mosquito Invasive-stage Malarial Parasite
Authors: Masao Yuda, Toshiki Sawai, Yasuo Chinzei
Journal: The Journal of Experimental Medicine (1999)

Invasion of the malarial parasite into a vector mosquito begins when the motile ookinete transverses the gut epithelium. Adhesive proteins that may mediate this invasive process have not been identified to date. We found that a molecule with an adhesive protein–like structure was expressed in the ookinete of Plasmodium berghei. This protein is structurally homologous to circumsporozoite protein and thrombospondin-related adhesive protein (TRAP)-related protein, CTRP, of Plasmodium falciparum. We named it P. berghei CTRP (PbCTRP) and report here its structure and manner of expression. PbCTRP has six integrin I region–like domains and seven thrombospondin-like domains in its putative extracellular region. This structure is similar to that of CTRP and TRAPs of malaria sporozoite. The putative transmembrane and cytoplasmic regions of PbCTRP, CTRP, and TRAP also have conserved amino acid sequences. PbCTRP is produced at least 10 h after fertilization when zygotes begin transformation to ookinetes. In the mature ookinete, PbCTRP is located mainly in the anterior cytoplasm. The staining pattern was also similar to TRAP in the sporozoite. We suggest that PbCTRP may play a role in ookinete invasive motility and belongs to a protein family together with TRAP and other structurally related proteins of apicomplexan parasites.
Patients With Acute Myeloid Leukemia and <i>RAS</i> Mutations Benefit Most From Postremission High-Dose Cytarabine: A Cancer and Leukemia Group B Study
Authors: Andreas Neubauer, Kati Maharry, Krzysztof Mrózek, Christian Thiede, Guido Marcucci, Peter Paschka, Robert J. Mayer, Richard A. Larson, Edison T. Liu, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2008)

RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo.One hundred eighty-five patients with AML achieving complete remission on Cancer and Leukemia Group B study 8525 and randomly assigned to one of three doses of cytarabine postremission were screened for RAS mutations. We assessed the impact of cytarabine dose on cumulative incidence of relapse (CIR) of patients with (mutRAS) and without (wild-type; wtRAS) RAS mutations.Thirty-four patients (18%) had RAS mutations. With 12.9 years median follow-up, the 10-year CIR was similar for mutRAS and wtRAS patients (65% v 73%; P = .31). However, mutRAS patients receiving high-dose cytarabine consolidation (HDAC; 3 g/m(2) every 12 hours on days 1, 3, and 5 or 400 mg/m(2)/d x 5 days) had the lowest 10-year CIR, 45%, compared with 68% for wtRAS patients receiving HDAC and 80% and 100%, respectively, for wtRAS and mutRAS patients receiving low-dose cytarabine (LDAC; 100 mg/m(2)/d x 5 days; overall comparison, P < .001). Multivariable analysis revealed an interaction of cytarabine dose and RAS status (P = .06). After adjusting for this interaction and cytogenetics (core binding factor [CBF] AML v non-CBF AML), wtRAS patients receiving HDAC had lower relapse risk than wtRAS patients receiving LDAC (hazard ratio [HR] = 0.67; P = .04); however, mutRAS patients receiving HDAC had greater reduction in relapse risk (HR = 0.28; P = .002) compared with mutRAS patients treated with LDAC.AML patients carrying mutRAS benefit from higher cytarabine doses more than wtRAS patients. This seems to be the first example of an activating oncogene mutation favorably modifying response to higher drug doses in AML.
Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity
Authors: Ashwin Woodhoo, Maria B Duran Alonso, Anna Droggiti, Mark Turmaine, Maurizio D'Antonio, David B Parkinson, Daniel K Wilton, Raya Al-Shawi, Paul Simons, Jie Shen, Francois Guillemot, Freddy Radtke, Dies Meijer, M Laura Feltri, Lawrence Wrabetz, Rhona Mirsky, Kristján R Jessen
Journal: Nature Neuroscience (2009)
Association Between Nicotine Withdrawal and Reward Responsiveness in Humans and Rats
Authors: Michele L. Pergadia, Andre Der-Avakian, Manoranjan S. D’Souza, Pamela A. F. Madden, Andrew C. Heath, Saul Shiffman, Athina Markou, Diego A. Pizzagalli
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Reward-related disturbances after withdrawal from nicotine are hypothesized to contribute to relapse to tobacco smoking but mechanisms underlying and linking such processes remain largely unknown. <h3>Objective</h3> To determine whether withdrawal from nicotine affects reward responsiveness (ie, the propensity to modulate behavior as a function of prior reinforcement experience) across species using translational behavioral assessments in humans and rats. <h3>Design, Setting, Participants</h3> Experimental studies used analogous reward responsiveness tasks in both humans and rats to examine whether reward responsiveness varied in (1) an ad libitum smoking condition compared with a 24-hour acute nicotine abstinence condition in 31 human smokers with (n = 17) or without (n = 14) a history of depression; (2) rats 24 hours after withdrawal from chronic nicotine (n = 19) or saline (n = 20); and (3) rats following acute nicotine exposure after withdrawal from either chronic nicotine or saline administration. <h3>Main Outcomes and Measures</h3> Performance on a reward responsiveness task under nicotine and nonnicotine conditions. <h3>Results</h3> In both human smokers and nicotine-treated rats, reward responsiveness was significantly reduced after 24-hour withdrawal from nicotine (<i>P</i> &lt; .05). In humans, withdrawal-induced deficits in reward responsiveness were greater in those with a history of depression. In rats previously exposed to chronic nicotine, acute nicotine reexposure long after withdrawal potentiated reward responsiveness (<i>P</i> &lt; .05). <h3>Conclusions and Relevance</h3> These findings across species converge in suggesting that organisms have diminished ability to modulate behavior as a function of reward during withdrawal of nicotine. This blunting may contribute to relapse to tobacco smoking, particularly in depression-vulnerable individuals, to reinstate responsiveness to natural rewards and to experience potentiated nicotine-induced reward responsiveness. Moreover, demonstration of behavioral homology across humans and rodents provides a strong translational framework for the investigation and development of clinical treatments targeting reward responsiveness deficits during early withdrawal of nicotine.
Bullous pemphigoid, polymyalgia rheumatica and thyroid disease
Authors: J. HOW, P. D. BEWSHER, L. STANKLER
Journal: British Journal of Dermatology (1980)

This paper describes the occurrence of bullous pemphigoid in a 71-year-old female patient who subsequently developed polymyalgia rheumatica and hyperthyroidism. The association of bullous pemphigoid with other autoimmune disorders is discussed.
Risk factors for extended-spectrum β-lactamase positivity in uropathogenic Escherichia coli isolated from community-acquired urinary tract infections
Authors: Ö.K. Azap, H. Arslan, K. Şerefhanoğlu, Ş. Çolakoğlu, H. Erdoğan, F. Timurkaynak, S.S. Senger
Journal: Clinical Microbiology and Infection (2009)
The Association Between Cortisol Response to Mental Stress and High-Sensitivity Cardiac Troponin T Plasma Concentration in Healthy Adults
Authors: Antonio I. Lazzarino, Mark Hamer, David Gaze, Paul Collinson, Andrew Steptoe
Journal: Journal of the American College of Cardiology (2013)

The objective of this study was to examine the association between cortisol response to mental stress and high-sensitivity cardiac troponin T (hs-cTnT) in healthy older individuals without history of cardiovascular disease (CVD). Mental stress is a recognized risk factor for CVD, although the mechanisms remain unclear. Cortisol, a key stress hormone, is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease. This cross-sectional study involved 508 disease-free men and women aged 53 to 76 years drawn from the Whitehall II epidemiological cohort. We evaluated salivary cortisol response to standardized mental stress tests (exposure) and hs-cTnT plasma concentration using a high-sensitivity assay (outcome). We measured coronary calcification using electron-beam dual-source computed tomography and Agatston scores. After adjustment for demographic and clinical variables associated with CVD as well as for inflammatory factors, we found a robust association between cortisol response and detectable hs-cTnT (odds ratio [OR]: 3.98; 95% confidence interval [CI]: 1.60 to 9.92; p = 0.003). The association remained when we restricted the analysis to participants without coronary calcification (n = 222; OR: 4.77; 95% CI: 1.22 to 18.72; p = 0.025) or when we further adjusted for coronary calcification in participants with positive Agatston scores (n = 286; OR: 7.39; 95% CI: 2.22 to 26.24; p = 0.001). We found that heightened cortisol response to mental stress was associated with detectable plasma levels of cTnT using high-sensitivity assays in healthy participants, independently of coronary atherosclerosis. Further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage.
Molecular basis of polymorphisms of human complement component C3.
Authors: M Botto, K Y Fong, A K So, C Koch, M J Walport
Journal: The Journal of Experimental Medicine (1990)

C3 exhibits two common allotypic variants that may be separated by gel electrophoresis and are called C3 fast (C3 F) and C3 slow (C3 S). C3 F, the less common variant, occurs at appreciable frequencies only in Caucasoid populations (gene frequency = 0.20). An increased prevalence of the C3 F allele has been reported in patients with partial lipodystrophy, IgA nephropathy, and Indian childhood hepatic cirrhosis. Studies of the genomic organization of the human C3 gene led to the identification of a single change (C to G) between C3 S and C3 F at nucleotide 364 in exon 3. This leads, at the translation level, to the substitution of an arginine residue (positively charged) in C3 S for a glycine residue (neutral) in C3 F. This substitution results in a polymorphic restriction site for the enzyme HhaI. The resulting restriction fragment length polymorphism (RFLP) was investigated using genomic DNA, amplified using the polymerase chain reaction; there was absolute concordance between the genomic polymorphism and the distribution of C3 S and C3 F in 50 normal subjects. The molecular basis of a second structural polymorphism, defined by the monoclonal antibody HAV 4-1, was also characterized. The polymorphic determinant was identified at codon 314 in the exon 9 of the beta chain where a leucine residue (HAV 4-1+) is substituted for a proline residue (HAV 4-1-). Identification of the amino acid sequences of these polymorphic variants will facilitate characterization of possible functional differences between different allotypes of C3. Three RFLPs (BamHI, EcoRI, and SstI) were located to introns in the C3 gene. There was no allelic association between these three RFLPs, or between the RFLPs and the C3 F/S polymorphic site. Genetic equilibration of these polymorphisms has occurred within a gene of 41 kb.
Descriptive epidemiology of World Health Organization grades II and III intracranial meningiomas in the United States
Authors: Varun R. Kshettry, Quinn T. Ostrom, Carol Kruchko, Ossama Al-Mefty, Gene H. Barnett, Jill S. Barnholtz-Sloan
Journal: Neuro-Oncology (2015)

Because World Health Organization (WHO) grades II and III meningiomas are relatively uncommon, there is limited literature on the descriptive epidemiology of these tumors, and the existing literature predates the 2000 WHO classification revisions. Our purpose was to provide a modern, population-based study of the descriptive epidemiology of WHO II and III meningiomas in the United States. The Central Brain Tumor Registry of the United States (CBTRUS) was queried for intracranial meningiomas categorized by WHO grade for the 2004­–2010 study period. Age-adjusted incidence (95% confidence interval in parentheses) per 100 000 population was calculated by age, sex, race, and ethnicity. Annual percent change (APC) was calculated using Joinpoint. From 2004 to 2010, the incidence of WHO II intracranial meningiomas increased from 0.28 (95% CI, 0.27­–0.29) to 0.30 (95% CI, 0.28–0.32), representing an APC of 3.6% (95%CI, 0.8%–6.5%). Conversely, from 2000–2010, the incidence of WHO III meningiomas decreased from 0.13 (95% CI, 0.11–0.14) to 0.06 (95%CI, 0.06–0.07), representing an APC of −5.4% (95% CI, −6.8% to −4.0%). From 2004 to 2010, the overall proportion of WHO I, II, and III intracranial meningiomas was 94.6%, 4.2%, and 1.2%, respectively. For WHO II/III meningiomas, females in the 35–64 year age group had a higher incidence than males in the same age group, whereas males in the ≥75 year age group ≥ had a higher incidence. Black and Asian Pacific Islander races were both associated with the highest incidence of WHO II/III meningiomas. Hispanic ethnicity was not associated with any difference in incidence. This study presents the most comprehensive evaluation of the modern descriptive epidemiology of WHO II and III meningiomas. Temporal trends likely reflect the 2000 WHO histological criteria revisions.