tbuckley/cabot-search huggingface dataset:
Functional decorations: post-translational modifications and heart disease delineated by targeted proteomics
Authors: Kiersten A Liddy, Melanie Y White, Stuart J Cordwell
Journal: Genome Medicine (2013)

The more than 300 currently identified post-translational modifications (PTMs) provides great scope for subtle or dramatic alteration of protein structure and function. Furthermore, the rapid and transient nature of many PTMs allows efficient signal transmission in response to internal and environmental stimuli. PTMs are predominantly added by enzymes, and the enzymes responsible (such as kinases) are thus attractive targets for therapeutic interventions. Modifications can be grouped according to their stability or transience (reversible versus irreversible): irreversible types (such as irreversible redox modifications or protein deamidation) are often associated with aging or tissue injury, whereas transient modifications are associated with signal propagation and regulation. This is particularly important in the setting of heart disease, which comprises a diverse range of acute (such as ischemia/reperfusion), chronic (such as heart failure, dilated cardiomyopathy) and genetic (such as hypertrophic cardiomyopathy) disease states, all of which have been associated with protein PTM. Recently the interplay between diverse PTMs has been suggested to also influence cellular function, with cooperation or competition for sites of modification possible. Here we discuss the utility of proteomics for examining PTMs in the context of the molecular mechanisms of heart disease.
Ventilation above Closing Volume Reduces Pulmonary Vascular Resistance Hysteresis
Authors: KEVIN M. CREAMER, LARYSSA L. McCLOUD, LYLE E. FISHER, INA C. EHRHART
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The aim of this study was to determine the relationship of pulmonary vascular resistance (PVR) hysteresis and lung volume, with special attention to the effects of ventilation around closing volume (CV). Isolated, blood-perfused canine left lower lung lobes (LLL) were incrementally inflated and deflated. Airway and pulmonary artery pressures (PAP) were recorded after each stepwise volume change. Constant blood flow was provided (600 ml/min) and the pulmonary vein pressure (PVP) was held constant at 5 cm H2O. PAP changes, therefore, were a direct index of PVR changes. Group 1 lobes underwent a full inflation from complete collapse to total lobe capacity (TLC) followed by a full deflation. Group 2 lobes underwent two deflation/inflation cycles, after an initial full inflation. These cycles, both beginning at TLC, had deflation end above and below CV, respectively. Significant PVR hysteresis was noted when the first inflation and deflation were compared. The maximum difference in PAP on deflation was 3.3 cm H2O or 11%. The mean decrease was 2.7 cm H2O for 18 lobes (p < 0.0001). The PAPs on all subsequent inflations or deflations that began above CV remained 9% lower than the initial inflation (n = 9, p < 0.0001), but were not different from each other. However, the final inflation which began from below CV resulted in a 30% return of PVR hysteresis (mean increase in PAP of 0.8 cm H2O, n = 7, p < 0.004). We conclude that there is hysteresis in the PVR response during ventilation, with decreased PVR during deflation relative to the initial inflation, that this hysteresis is absent when lung volume is maintained greater than CV, and that hysteresis returns when inflation occurs after deflation below CV.
Serological markers in progressive systemic sclerosis: clinical correlations.
Authors: L J Catoggio, R M Bernstein, C M Black, G R Hughes, P J Maddison
Journal: Annals of the Rheumatic Diseases (1983)

The relation between clinical and serological findings was studied in 75 patients with definite progressive systemic sclerosis (PSS). Antinuclear antibodies were detected by indirect immunofluorescence in 95% of the patients by means of HEp-2 cells. The centromere pattern was observed in 50% of the patients with calcinosis, Raynaud9s phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia (CREST) and only 7% of the group with diffuse disease. Precipitating antibodies to nuclear and cytoplasmic antigens were detected by immunodiffusion in 53% of the patients and identified as anti Scl-70 in 16 (21%). We confirmed that autoantibodies are very frequent in PSS but varied in specificity. A combination of immunodiffusion and indirect immunofluorescence was useful in detecting antibodies characteristic of PSS (i.e., anti-Scl-70 and anticentromere) in 51% of these patients. Anticentromere antibody has a high specificity for CREST and identifies patients with less severe disease (i.e., more prolonged course and less involvement of internal organs). Anti-Scl-70 was associated with a high frequency of lung involvement.
Antecedents of Personality Disorder in Childhood and Adolescence: Toward an Integrative Developmental Model
Authors: Filip De Fruyt, Barbara De Clercq
Journal: Annual Review of Clinical Psychology (2014)

Antecedents of personality disorder in childhood and adolescence have been a neglected area in official taxonomies of mental disorders such as the International Classification of Diseases or the different editions of the Diagnostic and Statistical Manual of Mental Disorders. An evolving research field, however, underscores the importance of antecedents for understanding psychopathology and personality pathology in adulthood. The current article summarizes the history, updates reviews, and incorporates new research findings into an integrative scheme for conceptualizing personality pathology in childhood and adolescence. Implications of this model for assessment, future research, and intervention are discussed.
Risk factors for death from asthma, chronic obstructive pulmonary disease, and cardiovascular disease after a hospital admission for asthma
Authors: H. F Guite, R. Dundas, P. G J Burney
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Patients with asthma have an increased risk of death from causes other than asthma. A study was undertaken to identify whether severity of asthma, its treatment, or associated co-morbidity were associated with increased risk of death from other causes. <h3>METHODS</h3> Eighty five deaths from all causes occurring within three years of discharge from hospital in a cohort of 2242 subjects aged 16–64 years admitted for asthma were compared with a random sample of 61 controls aged &lt;45 years and 61 aged ⩾45 years from the same cohort. <h3>RESULTS</h3> Deaths from asthma were associated with a history of clinically severe asthma (OR 6.29 (95% CI 1.84 to 21.52)), chest pain (OR 3.78 (95% CI 1.06 to 13.5)), biochemical or haematological abnormalities at admission (OR 4.12 (95% CI 1.36 to 12.49)), prescription of ipratropium bromide (OR 4.04 (95% CI 1.47 to 11.13)), and failure to prescribe inhaled steroids on discharge (OR 3.45 (95% CI 1.35 to 9.10)). Deaths from chronic obstructive pulmonary disease (COPD) were associated with lower peak expiratory flow rates (OR 2.56 (95% CI 1.52 to 4.35) for each 50 l/min change), a history of smoking (OR 5.03 (95% CI 1.17 to 21.58)), prescription of ipratropium bromide (OR 7.75 (95% CI 2.21 to 27.14)), and failure to prescribe inhaled steroids on discharge (OR 3.33 (95% CI 0.95 to 11.10)). Cardiovascular deaths were more common among those prescribed ipratropium bromide on discharge (OR 3.55 (95% CI 1.05 to 11.94)) and less likely in those admitted after an upper respiratory tract infection (OR 0.21 (95% CI 0.05 to 0.95)). Treatment with ipratropium bromide at discharge was associated with an increased risk of death from asthma even after adjusting for peak flow, COPD and cardiovascular co-morbidity, ever having smoked, and age at onset of asthma. <h3>CONCLUSIONS</h3> Prescription of inhaled steroids on discharge is important even for those patients with co-existent COPD and asthma. Treatment with ipratropium at discharge is associated with increased risk of death from asthma even after adjustment for a range of markers of COPD. These results need to be tested in larger studies.
Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C
Authors: Alessio Aghemo, Raffaele De Francesco
Journal: Gut (2014)

With the introduction of direct-acting antivirals (DAA), the treatment for chronic hepatitis C is evolving at an astonishingly rapid pace.1 Among DAAs, HCV NS5A inhibitors show substantial promise as anti-HCV therapeutics. NS5A inhibitors in clinical development include daclatasvir (DCV), ledipasvir, ombitasvir and MK-8742.2 With in vitro anti-HCV activities in the low picomolar range, these represent the most potent class of DAAs to target HCV. The HCV NS5A protein is known to function in multiple aspects of the HCV life cycle, including roles in viral replication and assembly, as well as complex interactions with cellular factors. Not being associated with any measurable enzymatic activity, NS5A was not considered ‘druggable’ for a very long time. In fact, the first small-molecule NS5A inhibitors were discovered by random screening using the HCV replicon system. The initial lead compounds had only moderate potency, but subsequent medicinal chemistry efforts resulted in the discovery of drugs with unparalleled antiviral activity that are characterised by highly symmetrical dimeric structure.3 The most studied of these ‘palindromic’ NS5A inhibitor class is DCV4 (formerly BMS-790052), a DAA active against a broad range of HCV genotypes for which regulatory approval both in interferon (IFN)-containing or IFN-free regimens is currently being sought. Sequencing of replicons resistant to DCV and related compounds identified NS5A as their molecular target.5 ,6 In particular, variants of NS5A M28, Q30, L31 and Y93 were found to be the most common mutations conferring broad resistance to this class of antivirals. Y93, the …
Theory in Behavioral Diabetes Research
Authors: Mark F. Peyrot
Journal: Diabetes Care (2001)

A recent editorial regarding diabetes education discussed the difficulty of doing quality research in this area (1). Behavioral research is inherently difficult (behavioral researchers like to call it “hard science” as opposed to the “easy science” of other fields). However, I will not discuss methods per se, focusing instead on the role of theory. Below I address the ways that theory can inform research, and I offer some thoughts about the role of extra-scientific considerations in research. What I say is particularly addressed to behavioral researchers, but much of it is relevant to other researchers as well.

The role of theory in behavioral diabetes research is poorly understood. Many see theory as a grandiose conceptual scheme with little relevance to research. But it has been noted that there is nothing so practical as a good theory. The problem is with how theory is used. For example, consider the use of theory in recent research on behavioral interventions in diabetes. A recent study tested a behavioral intervention based on the Transtheoretical Model (TTM), currently a popular theory, against standard care (i.e., standard care against standard care plus a behavioral intervention) (2). To the surprise of no one familiar with behavioral interventions, adding the behavioral intervention produced better outcomes. But did this “prove” TTM, or did it simply demonstrate that behavioral interventions work? And when Anderson et al. (3) found benefit from a behavioral intervention based on empowerment concepts, did this “prove” a theory, or only that another behavioral intervention worked? Clearly these are not tests of a theory; they merely demonstrate that, behaviorally speaking, something is better than nothing. This research approach “assumes” the theory by building it into the intervention. Similarly, I have seen several unpublished studies that have proposed elaborate formulations of “stages of change” that were reducible empirically …
TCT-239 Impact Of Overlapping Site On 9 Month Angiographic Results After Multiple Overlapping Everolimus-eluting Stents Implantation: A Serial Quantitative Coronary Angiography Analysis
Authors: Kenya Nasu, Yuji Oikawa, Yuichi Ujiie, Atsunori Okamura, Ryo Gotoh, Masaki Tanabe, Tadanori Aizawa, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2014)
Genome-wide deletion mutant analysis reveals genes required for respiratory growth, mitochondrial genome maintenance and mitochondrial protein synthesis in Saccharomyces cerevisiae
Authors: Sandra Merz, Benedikt Westermann
Journal: Genome biology (2009)

The mitochondrial respiratory chain produces metabolic energy by oxidative phosphorylation. Biogenesis of the respiratory chain requires the coordinated expression of two genomes: the nuclear genome encoding the vast majority of mitochondrial proteins, and the mitochondrial genome encoding a handful of mitochondrial proteins. The understanding of the molecular processes contributing to respiratory chain assembly and maintenance requires the systematic identification and functional analysis of the genes involved.We pursued a systematic, genome-wide approach to define the sets of genes required for respiratory activity and maintenance and expression of the mitochondrial genome in yeast. By comparative gene deletion analysis we found an unexpected phenotypic plasticity among respiratory-deficient mutants, and we identified ten previously uncharacterized genes essential for respiratory growth (RRG1 through RRG10). Systematic functional analysis of 319 respiratory-deficient mutants revealed 16 genes essential for maintenance of the mitochondrial genome, 88 genes required for mitochondrial protein translation, and 10 genes required for expression of specific mitochondrial gene products. A group of mutants acquiring irreversible damage compromising respiratory capacity includes strains defective in assembly of the cytochrome c oxidase that were found to be particularly sensitive to aging.These data advance the understanding of the molecular processes contributing to maintenance of the mitochondrial genome, mitochondrial protein translation, and assembly of the respiratory chain. They revealed a number of previously uncharacterized components, and provide a comprehensive picture of the molecular processes required for respiratory activity in a simple eukaryotic cell.
Possible role for C-reactive protein in the human natural killer cell response.
Authors: L L Baum, K K James, R R Glaviano, H Gewurz
Journal: The Journal of Experimental Medicine (1983)

Functional NK activity can be removed from human PBL and from phagocyte- and T cell-depleted LGL preparations by treatment with antisera specific for C-reactive protein (CRP) in the presence of complement (C). Pretreatment of NK effector cells with high concentrations of anti-CRP in the absence of C also depletes functional activity. These results indicate that CRP or an antigenically similar molecule is present on a population of NK effector cells. Fluorescent antibody studies in which biotin-avidin amplification was used confirm the presence of surface CRP (S-CRP) on a small percentage of nonphagocytic peripheral blood mononuclear cells. S-CRP readily caps off, which suggest that removal by capping obviates killing by this cell population. This indicates that S-CRP or a molecule that co-caps with S-CRP may be required for successful effector-target cell interaction. The addition of exogenous CRP or CRP-CPS complexes, however, does not alter NK responses. A subpopulation of lymphoid cells responsible for functional NK activity therefore appears to bear surface CRP.
Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health
Authors: Laurent Peyrin-Biroulet, Alarcos Cieza, William J Sandborn, Michaela Coenen, Yehuda Chowers, Toshifumi Hibi, Nenad Kostanjsek, Gerold Stucki, Jean-Frédéric Colombel
Journal: Gut (2011)

<h3>Objective</h3> The impact of inflammatory bowel disease (IBD) on disability remains poorly understood. The World Health Organization9s integrative model of human functioning and disability in the International Classification of Functioning, Disability and Health (ICF) makes disability assessment possible. The ICF is a hierarchical coding system with four levels of details that includes over 1400 categories. The aim of this study was to develop the first disability index for IBD by selecting most relevant ICF categories that are affected by IBD. <h3>Methods</h3> Relevant ICF categories were identified through four preparatory studies (systematic literature review, qualitative study, expert survey and cross-sectional study), which were presented at a consensus conference. Based on the identified ICF categories, a questionnaire to be filled in by clinicians, called the ‘IBD disability index’, was developed. <h3>Results</h3> The four preparatory studies identified 138 second-level categories: 75 for systematic literature review (153 studies), 38 for qualitative studies (six focus groups; 27 patients), 108 for expert survey (125 experts; 37 countries; seven occupations) and 98 for cross-sectional study (192 patients; three centres). The consensus conference (20 experts; 17 countries) led to the selection of 19 ICF core set categories that were used to develop the IBD disability index: seven on body functions, two on body structures, five on activities and participation and five on environmental factors. <h3>Conclusions</h3> The IBD disability index is now available. It will be used in studies to evaluate the long-term effect of IBD on patient functional status and will serve as a new endpoint in disease-modification trials.
Temozolomide As Initial Treatment for Adults With Low-Grade Oligodendrogliomas or Oligoastrocytomas and Correlation With Chromosome 1p Deletions
Authors: K. Hoang-Xuan, L. Capelle, M. Kujas, S. Taillibert, H. Duffau, J. Lejeune, M. Polivka, E. Crinière, Y. Marie, K. Mokhtari, A.F. Carpentier, F. Laigle, J.M. Simon, P. Cornu, P. Broët, M. Sanson, J.Y. Delattre
Journal: Journal of Clinical Oncology (2004)

To determine the response rate of low-grade oligodendroglial tumors (LGOT) to temozolomide (TMZ) as initial treatment and to evaluate the predictive value of chromosome 1p deletion on the radiologic response.Adult patients with pathologically proven LGOT with progressive disease on magnetic resonance imaging (MRI) were eligible for the study. TMZ was administered at the starting dose of 200 mg/m2/d for 5 days, repeated every 28 days. Response was evaluated clinically and by central review of MRIs. Chromosome 1p and 19q deletions were detected by the loss of heterozygosity technique.Sixty consecutive patients were included in the study. At the time of analysis, the median number of TMZ cycles delivered was 11. Clinically, 51% of patients improved, particularly those with uncontrolled epilepsy. The objective radiologic response rate was 31% (17% partial response and 14% minor response), whereas 61% of patients had stable disease and 8% experienced disease progression. The median time to maximum tumor response was 12 months (range, 5 to 20 months). Myelosuppression was the most frequent side effect, with grade 3 to 4 toxicity in 8% of patients. Loss of chromosome 1p was associated with objective tumor response (P < .004).TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer–subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306
Authors: S. Stintzing, L. Fischer von Weikersthal, T. Decker, U. Vehling-Kaiser, E. Jäger, T. Heintges, C. Stoll, C. Giessen, D.P. Modest, J. Neumann, A. Jung, T. Kirchner, W. Scheithauer, V. Heinemann
Journal: Annals of Oncology (2012)
Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders
Authors: Sarah K Westbury, Ernest Turro, Daniel Greene, Claire Lentaigne, Anne M Kelly, Tadbir K Bariana, Ilenia Simeoni, Xavier Pillois, Antony Attwood, Steve Austin, Sjoert BG Jansen, Tamam Bakchoul, Abi Crisp-Hihn, Wendy N Erber, Rémi Favier, Nicola Foad, Michael Gattens, Jennifer D Jolley, Ri Liesner, Stuart Meacham, Carolyn M Millar, Alan T Nurden, Kathelijne Peerlinck, David J Perry, Pawan Poudel, Sol Schulman, Harald Schulze, Jonathan C Stephens, Bruce Furie, Peter N Robinson, Chris van Geet, Augusto Rendon, Keith Gomez, Michael A Laffan, Michele P Lambert, Paquita Nurden, Willem H Ouwehand, Sylvia Richardson, Andrew D Mumford, Kathleen Freson
Journal: Genome Medicine (2015)
Quality of Cancer Family History and Referral for Genetic Counseling and Testing Among Oncology Practices: A Pilot Test of Quality Measures As Part of the American Society of Clinical Oncology Quality Oncology Practice Initiative
Authors: Marie E. Wood, Pamela Kadlubek, Trang H. Pham, Dana S. Wollins, Karen H. Lu, Jeffrey N. Weitzel, Michael N. Neuss, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2014)

Family history of cancer (CFH) is important for identifying individuals to receive genetic counseling/testing (GC/GT). Prior studies have demonstrated low rates of family history documentation and referral for GC/GT.CFH quality and GC/GT practices for patients with breast (BC) or colon cancer (CRC) were assessed in 271 practices participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative in fall 2011.A total of 212 practices completed measures regarding CFH and GC/GT practices for 10,466 patients; 77.4% of all medical records reviewed documented presence or absence of CFH in first-degree relatives, and 61.5% of medical records documented presence or absence of CFH in second-degree relatives, with significantly higher documentation for patients with BC compared with CRC. Age at diagnosis was documented for all relatives with cancer in 30.7% of medical records (BC, 45.2%; CRC, 35.4%; P ≤ .001). Referall for GC/GT occurred in 22.1% of all patients with BC or CRC. Of patients with increased risk for hereditary cancer, 52.2% of patients with BC and 26.4% of those with CRC were referred for GC/GT. When genetic testing was performed, consent was documented 77.7% of the time, and discussion of results was documented 78.8% of the time.We identified low rates of complete CFH documentation and low rates of referral for those with BC or CRC meeting guidelines for referral among US oncologists. Documentation and referral were greater for patients with BC compared with CRC. Education and support regarding the importance of accurate CFH and the benefits of proactive high-risk patient management are clearly needed.