tbuckley/cabot-search huggingface dataset:
Recurrent Adaptation in RNA Interference Genes Across the Drosophila Phylogeny
Authors: B. Kolaczkowski, D. N. Hupalo, A. D. Kern
Journal: Molecular Biology and Evolution (2010)

RNA interference (RNAi) is quickly emerging as a vital component of genome organization, gene regulation, and immunity in Drosophila and other species. Previous studies have suggested that, as a whole, genes involved in RNAi are under intense positive selection in Drosophila melanogaster. Here, we characterize the extent and patterns of adaptive evolution in 23 known Drosophila RNAi genes, both within D. melanogaster and across the Drosophila phylogeny. We find strong evidence for recurrent protein-coding adaptation at a large number of RNAi genes, particularly those involved in antiviral immunity and defense against transposable elements. We identify specific functional domains involved in direct protein–RNA interactions as particular hotspots of recurrent adaptation in multiple RNAi genes, suggesting that targeted coadaptive arms races may be a general feature of RNAi evolution. Our observations suggest a predictive model of how selective pressures generated by evolutionary arms race scenarios may affect multiple genes across protein interaction networks and other biochemical pathways.
Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications
Authors: F. Nolé, E. Munzone, L. Zorzino, I. Minchella, M. Salvatici, E. Botteri, M. Medici, E. Verri, L. Adamoli, N. Rotmensz, A. Goldhirsch, M.T. Sandri
Journal: Annals of Oncology (2007)
Albuterol treatment for children with asthma: A comparison of inhaled powder and aerosol
Authors: J.P. Kemp, C.T. Furukawa, E.A. Bronsky, J. Grossman, R.F. Lemanske, L.E. Mansfield, S. Murphy, P.H. Ratner, M.E. Reese, P.R. Rogenes, S.L Spector, D.G. Tinkelman
Journal: Journal of Allergy and Clinical Immunology (1989)
Deriving intentionality from artifacts
Authors: J. Scott Jordan
Journal: Behavioral and Brain Sciences (2002)

Cognitive psychologists tend to treat intentionality as a control variable during experiments, yet ignore it when generating mechanistic descriptions of performance. Wynn's work brings this conflict into striking relief and, when considered in relation to recent neurophysiological findings, makes it clear that intentionality can be regarded mechanistically if one defines it as the planning of distal effects.
Coordinate regulation of gallbladder motor function in the gut-liver axis
Authors: Piero Portincasa, Agostino Di Ciaula, Helen H. Wang, Giuseppe Palasciano, Karel J. van Erpecum, Antonio Moschetta, David Q.-H. Wang
Journal: Hepatology (2008)

Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation.
Prophylaxis and Aspergillosis — Has the Principle Been Proven?
Authors: Ben E. De Pauw, J. Peter Donnelly
Journal: New England Journal of Medicine (2007)

Invasive fungal diseases contribute substantially to death and illness associated with the prolonged, profound neutropenia resulting from intensive chemotherapy for hematologic cancers and from myeloablation for allogeneic hematopoietic stem-cell transplantation. In addition, the development of graft-versus-host disease (GVHD) puts transplant recipients at risk for infection for several weeks or months after engraftment.1 Given the high mortality associated with invasive fungal diseases and our inability to recognize active cases reliably, it is not surprising that prophylaxis is perceived as a sensible therapeutic approach.More than a decade ago, fluconazole was shown to be effective for preventing candida infection.2 However, aspergillus species . . .
P155 Visualisation of Airway Nerves in Chronic Cough: Towards the Identification of the Human ‘Cough Receptor’
Authors: PW West, BJ Canning, EC Hilton, S Khalid, K Holt, R Abdulqawi, AA Woodcock, JA Smith
Journal: Thorax (2012)

<h3>Introduction</h3> The spinal and vagal innervation of the respiratory tract is well defined, particularly in animals. These discoveries include the identification of pathways involved in provoking cough and descriptions of the guinea pig ‘cough receptor’. However, many of the immunochemical features of the airway afferents described in animals have yet to be defined in humans, yet plasticity of these airway afferents may be important in the pathophysiology of chronic cough. <h3>Objectives</h3> To define and characterise the innervation present in bronchoscopic biopsies from patients with chronic cough. We aimed to carry out the first ever whole mount immunohistochemical studies of airway nerves in cough patients, a technique that should improve visualisation of these neuronal structures and their sites of termination. <h3>Methods</h3> Biopsy tissue was gifted from patients undergoing clinical investigation for chronic cough. Tissue, sampled from throughout the extrapulmonary airways, was immediately fixed in 4% paraformaldehyde. Non-specific antibody binding was blocked using 10% normal serum and 1% skimmed milk powder, diluted in PBS, before application of primary antibodies. Polyclonal rabbit anti-PGP9.5 (Ultraclone, UK) and monoclonal mouse anti-neurofilament (NF200, Leica Biosystems, UK) were applied at a dilution of 1:1000 and 1:200 respectively. Primary antibody binding was detected using appropriate Alexa-fluor conjugated secondary antibodies and whole mount preparations were visualised using epifluorescence and confocal microscopy. Images of biopsy staining were subject to morphometric analysis. <h3>Results</h3> Many epithelial, subepithelial and intramuscular fibres were detected using both antibodies. Co-staining revealed that only PGP9.5 defined pulmonary neuroendocrine cells and better elucidated varicose epithelial fibres. A proportion of all fibre types were only immunopositive for one marker. Notably NF200 exclusively detected some epithelial fibres and a group of larger diameter neurons (Ø3–6 µm) some of which are consistent with observations of Aδ-fibre airway mechanoreceptors. <h3>Conclusions</h3> We have described neuronal structures in whole-mount preparations of tissue from patients suffering from chronic cough. Notably, we described a population of PGP9.5 negative fibres within the airways. Some of these fibres are morphologically consistent with thinly myelinated Aδ-fibres described in animal models as ‘cough receptors’. These ongoing studies could help define the plasticity of airway nerves in patients with chronic cough.
Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis
Authors: D. Moro-Sibilot, S. Lantuejoul, S. Diab, N. Moulai, A. Aubert, J. F. Timsit, C. Brambilla, P. Y. Brichon, E. Brambilla
Journal: European Respiratory Journal (2007)

Lung carcinoma with a basaloid pattern (BC) is classified as either a basaloid variant of squamous cell carcinoma (SCC) or as variant of large cell carcinoma (LCC) depending on the presence of a squamous component. In a previous study of 37 cases, the present authors showed that BC presented with a shorter median and overall survival. In order to confirm its clinical significance in a larger series, 90 BC, including 46 basaloid variants of LCC and 44 basaloid variants of SCC, were compared with 1,328 other nonsmall cell lung carcinoma (NSCLC) with regard to clinical features and survival. The survival of basaloid variants of LCC and SCC was comparable. Median and overall survival were significantly lower for BC than for NSCLC in stage I–II patients, with a median survival of 29 and 49 months, respectively, and 5-yr survival rates of 27 and 44% for BC and NSCLC. When disease-specific survival was considered, BC had a shorter survival than both NSCLC and SCC. Basaloid pattern confers a poor prognosis in nonsmall cell lung carcinoma, especially in stage I–II patients, suggesting that lung carcinoma with a basaloid pattern is not only a variant of squamous cell carcinoma or large cell carcinoma, but is a unique entity with a significantly poor prognosis.
Suicide Prevention Strategies
Authors: J. John Mann, Alan Apter, Jose Bertolote, Annette Beautrais, Dianne Currier, Ann Haas, Ulrich Hegerl, Jouko Lonnqvist, Kevin Malone, Andrej Marusic, Lars Mehlum, George Patton, Michael Phillips, Wolfgang Rutz, Zoltan Rihmer, Armin Schmidtke, David Shaffer, Morton Silverman, Yoshitomo Takahashi, Airi Varnik, Danuta Wasserman, Paul Yip, Herbert Hendin
Journal: JAMA (2005)

In 2002, an estimated 877,000 lives were lost worldwide through suicide. Some developed nations have implemented national suicide prevention plans. Although these plans generally propose multiple interventions, their effectiveness is rarely evaluated.To examine evidence for the effectiveness of specific suicide-preventive interventions and to make recommendations for future prevention programs and research.Relevant publications were identified via electronic searches of MEDLINE, the Cochrane Library, and PsychINFO databases using multiple search terms related to suicide prevention. Studies, published between 1966 and June 2005, included those that evaluated preventative interventions in major domains; education and awareness for the general public and for professionals; screening tools for at-risk individuals; treatment of psychiatric disorders; restricting access to lethal means; and responsible media reporting of suicide.Data were extracted on primary outcomes of interest: suicidal behavior (completion, attempt, ideation), intermediary or secondary outcomes (treatment seeking, identification of at-risk individuals, antidepressant prescription/use rates, referrals), or both. Experts from 15 countries reviewed all studies. Included articles were those that reported on completed and attempted suicide and suicidal ideation; or, where applicable, intermediate outcomes, including help-seeking behavior, identification of at-risk individuals, entry into treatment, and antidepressant prescription rates. We included 3 major types of studies for which the research question was clearly defined: systematic reviews and meta-analyses (n = 10); quantitative studies, either randomized controlled trials (n = 18) or cohort studies (n = 24); and ecological, or population- based studies (n = 41). Heterogeneity of study populations and methodology did not permit formal meta-analysis; thus, a narrative synthesis is presented.Education of physicians and restricting access to lethal means were found to prevent suicide. Other methods including public education, screening programs, and media education need more testing.Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates. Other interventions need more evidence of efficacy. Ascertaining which components of suicide prevention programs are effective in reducing rates of suicide and suicide attempt is essential in order to optimize use of limited resources.
Distal Renal Tubular Acidosis in Mice Lacking the AE1 (Band3) Cl−/HCO3 − Exchanger (slc4a1)
Authors: Paul A. Stehberger, Boris E. Shmukler, Alan K. Stuart-Tilley, Luanne L. Peters, Seth L. Alper, Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2007)

Mutations in the human gene that encodes the AE1 Cl−/HCO3− exchanger (SLC4A1) cause autosomal recessive and dominant forms of distal renal tubular acidosis (dRTA). A mouse model that lacks AE1/slc4a1 (slc4a1−/−) exhibited dRTA characterized by spontaneous hyperchloremic metabolic acidosis with low net acid excretion and, inappropriately, alkaline urine without bicarbonaturia. Basolateral Cl−/HCO3− exchange activity in acid-secretory intercalated cells of isolated superfused slc4a1−/− medullary collecting duct was reduced, but alternate bicarbonate transport pathways were upregulated. Homozygous mice had nephrocalcinosis associated with hypercalciuria, hyperphosphaturia, and hypocitraturia. A severe urinary concentration defect in slc4a1−/− mice was accompanied by dysregulated expression and localization of the aquaporin-2 water channel. Mice that were heterozygous for the AE1-deficient allele had no apparent defect. Thus, the slc4a1−/− mouse is the first genetic model of complete dRTA and demonstrates that the AE1/slc4a1 Cl−/HCO3− exchanger is required for maintenance of normal acid-base homeostasis by distal renal regeneration of bicarbonate in the mouse as well as in humans.
Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.
Authors: P D Collins, S Marleau, D A Griffiths-Johnson, P J Jose, T J Williams
Journal: The Journal of Experimental Medicine (1995)

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.
Short-term Clinical Effects of Tolvaptan, an Oral Vasopressin Antagonist, in Patients Hospitalized for Heart Failure&lt;SUBTITLE&gt;The EVEREST Clinical Status Trials&lt;/SUBTITLE&gt;
Authors: Mihai Gheorghiade
Journal: JAMA (2007)

Outcome Study With Tolvaptan (EVEREST) Investigators HEART FAILURE (HF) IS A MAjor international public health problem presenting significant medical and economic challenges.][5][6][7][8] Congestion characterized by dyspnea, edema, rales, jugular venous dis-See also pp
A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers
Authors: Cláudia Trindade Nunes, Kelly L. Miners, Garry Dolton, Chris Pepper, Chris Fegan, Malcolm D. Mason, Stephen Man
Journal: Cancer Research (2011)

Cancer cells frequently exhibit defects in apoptosis, which contribute to increased survival and chemotherapeutic resistance. For example, genetic mutations or abnormal proteasomal degradation can reduce expression of Bax which limits apoptosis. In cancers where abnormal proteasomal degradation of Bax occurs, we hypothesized that Bax peptides that bind to human leukocyte antigen (HLA) class I molecules would be generated for presentation to CD8(+) T cells. To test this hypothesis, we generated T cells against pooled Bax peptides, using the blood of healthy human donors. Although T-cell responses were of low frequency (0.15%), a CD8(+) T-cell clone (KSIVB17) was isolated that optimally recognized Bax(136-144) peptide (IMGWTLDFL) presented by HLA-A*0201. KSIVB17 was able to recognize and kill a variety of HLA-matched cancer cells including primary tumor cells from chronic lymphocytic leukemia (CLL). No reactivity was seen against HLA-matched, nontransformed cells such as PHA blasts and skin fibroblasts. Furthermore, KSIVB17 reactivity corresponded with the proteasomal degradation patterns of Bax protein observed in cancer cells. Taken together, our findings suggest a new concept for tumor antigens based on regulatory proteins that are ubiquitously expressed in normal cells, but that have abnormally enhanced degradation in cancer cells. Bax degradation products offer candidate immune antigens in cancers such as CLL in which increased Bax degradation correlates with poor clinical prognosis.
Surgery of the rheumatoid elbow.
Authors: W A Souter
Journal: Annals of the Rheumatic Diseases (1990)

I suggest that for too long the problem of the rheumatoid elbow, particularly the need for surgical intervention, has been underestimated. Where the latter has been advocated the philosophy has been adopted that synovectomy and debridement with excision of the head of the radius is probably all that is required, or that in the late case excision arthroplasty may yield an adequate result. I suggest that these approaches are no longer tenable. Synovectomy and debridement with or without excision of the head of the radius does indeed retain an extremely valuable place in the management of stage 1, 2, and early stage 3 disease. In the later stages of the disease, however, serious consideration must now be given to total joint replacement, the results of which can be remarkably successful and durable, and the complications from which can now be contained within acceptable limits provided that the operating team is fully experienced. It must also be stressed how necessary it is in the medical or combined clinic to pursue careful clinical and radiological monitoring of the rheumatoid elbow so that signs of dangerous deterioration can be recognised early, and surgery applied at a time when optimal conditions for the particular surgical weapons to be used still exist.
Long-Term Survival of Patients With Supraclavicular Metastases at Diagnosis of Breast Cancer
Authors: Ivo A. Olivotto, Boon Chua, Sharon J. Allan, Caroline H. Speers, Stephen Chia, Joseph Ragaz
Journal: Journal of Clinical Oncology (2003)

Patients with supraclavicular metastases at diagnosis of breast cancer were classified between 1987 and 2002 as having stage M(1) breast cancer according to the tumor-node-metastasis (TNM) system. The 2003 edition of the TNM staging guidelines has classified such patients as having stage IIIC disease. To determine relative prognosis, we compared long-term survival in a population-based cohort of patients with isolated supraclavicular metastases (nodal-M(1)) to outcomes of patients with stage IIIB or M(1) (other) disease at presentation.Among patients with breast cancer and known tumor stage referred to the British Columbia Cancer Agency from 1976 to 1985, 336 IIIB, 233 M(1), and 51 nodal-M(1) patients were identified. Actuarial overall and breast cancer-specific survival rates were determined to 20 years.Overall survival at 20 years was 13.2% for nodal-M(1) cases (95% confidence interval [CI], 5% to 26%), 9.4% for IIIB cases (95% CI, 6% to 14%), and 1.3% for M(1) (other) cases (95% CI, 0.4% to 3.5%; log-rank P <.0005). Overall survival was similar between nodal-M(1) and IIIB cases (P =.27). Breast cancer-specific survival at 20 years was 24.1% for nodal-M(1) cases (95% CI, 13% to 37%), 30.2% for IIIB cases (95% CI, 23% to 38%), and 3.9% for M(1) (other) cases (95% CI, 2% to 8%; log-rank P <.0005). Breast cancer-specific survival was significantly different for nodal-M(1) cases compared with either IIIB or M(1) (other) cases (P =.008 for both).Patients with supraclavicular metastases at diagnosis have significantly better outcomes than patients with M(1) (other) disease and overall survival similar to patients with IIIB disease. Reclassification as stage IIIC is appropriate for patients with breast cancer who present with supraclavicular nodal metastases alone.
Association between Microdeletion and Microduplication at 16p11.2 and Autism
Authors: Lauren A. Weiss, Yiping Shen, Joshua M. Korn, Dan E. Arking, David T. Miller, Ragnheidur Fossdal, Evald Saemundsen, Hreinn Stefansson, Todd Green, Orah S. Platt, Douglas M. Ruderfer, Christopher A. Walsh, David Altshuler, Aravinda Chakravarti, Rudolph E. Tanzi, Kari Stefansson, Susan L. Santangelo, James F. Gusella, Pamela Sklar, Bai-Lin Wu, Mark J. Daly
Journal: New England Journal of Medicine (2008)

Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role.As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland.Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor.We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations.