tbuckley/cabot-search huggingface dataset:
Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes
Authors: Heather C. Mefford, Andrew J. Sharp, Carl Baker, Andy Itsara, Zhaoshi Jiang, Karen Buysse, Shuwen Huang, Viv K. Maloney, John A. Crolla, Diana Baralle, Amanda Collins, Catherine Mercer, Koen Norga, Thomy de Ravel, Koen Devriendt, Ernie M.H.F. Bongers, Nicole de Leeuw, William Reardon, Stefania Gimelli, Frederique Bena, Raoul C. Hennekam, Alison Male, Lorraine Gaunt, Jill Clayton-Smith, Ingrid Simonic, Soo Mi Park, Sarju G. Mehta, Serena Nik-Zainal, C. Geoffrey Woods, Helen V. Firth, Georgina Parkin, Marco Fichera, Santina Reitano, Mariangela Lo Giudice, Kelly E. Li, Iris Casuga, Adam Broomer, Bernard Conrad, Markus Schwerzmann, Lorenz Räber, Sabina Gallati, Pasquale Striano, Antonietta Coppola, John L. Tolmie, Edward S. Tobias, Chris Lilley, Lluis Armengol, Yves Spysschaert, Patrick Verloo, Anja De Coene, Linde Goossens, Geert Mortier, Frank Speleman, Ellen van Binsbergen, Marcel R. Nelen, Ron Hochstenbach, Martin Poot, Louise Gallagher, Michael Gill, Jon McClellan, Mary-Claire King, Regina Regan, Cindy Skinner, Roger E. Stevenson, Stylianos E. Antonarakis, Caifu Chen, Xavier Estivill, Björn Menten, Giorgio Gimelli, Susan Gribble, Stuart Schwartz, James S. Sutcliffe, Tom Walsh, Samantha J.L. Knight, Jonathan Sebat, Corrado Romano, Charles E. Schwartz, Joris A. Veltman, Bert B.A. de Vries, Joris R. Vermeesch, John C.K. Barber, Lionel Willatt, May Tassabehji, Evan E. Eichler
Journal: New England Journal of Medicine (2008)

Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.
Galectins and Immune Responses—Just How Do They Do Those Things They Do?
Authors: Sandra Thiemann, Linda G. Baum
Journal: Annual Review of Immunology (2016)

Galectins are a family of mammalian carbohydrate-binding proteins expressed by many cell types. Galectins can function intracellularly and can also be secreted to bind to cell surface glycoconjugate counterreceptors. Some galectins are made by immune cells, whereas other galectins are secreted by different cell types, such as endothelial or epithelial cells, and bind to immune cells to regulate immune responses. Galectin binding to a single glycan ligand is a low-affinity interaction, but the multivalency of galectins and the glycan ligands presented on cell surface glycoproteins results in high-avidity binding that can reversibly scaffold or cluster these glycoproteins. Galectin binding to a specific glycoprotein counterreceptor is regulated in part by the repertoire of glycosyltransferase enzymes (which make the glycan ligands) expressed by that cell, and the effect of galectin binding results from clustering or retention of specific glycoprotein counterreceptors bearing these specific ligands.
Increased Gelatinolytic Activity in Bronchoalveolar Lavage Fluid in Stable Lung Transplant Recipients
Authors: CONNIE A. TRELLO, DEBBIE A. WILLIAMS, CESAR A. KELLER, COURTNEY CRIM, ROBERT O. WEBSTER, JILL A. OHAR
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Proteolytic enzymes have been proposed to play a role in the pathogenesis of various inflammatory pulmonary diseases accompanied by parenchymal remodeling. To assess the role of inflammatory cells and proteolytic enzymes in the development of chronic allograft rejection after lung transplantation, bronchoalveolar lavage fluid (BALF) samples from clinically stable lung transplant (LT) recipients (i.e., without evidence of active infection or rejection), heart transplant (HT) recipients, and healthy volunteers (NL) were analyzed for total white blood cell (WBC) count and differential cell count, along with gelatinolytic/type IV collagenolytic activity. The LT group displayed a significantly increased total WBC count, neutrophil count, and percent neutrophils compared with the NL group, confirming the presence of inflammation. Furthermore, gelatin zymography revealed a significant increase in activity of the 72 and 92 kD gelatinases in the LT group compared with the NL group. A positive correlation existed between neutrophil counts and the increase in proteolytic activity. Immunosuppressive therapy did not account for the findings, since no significant difference in cell counts or proteolytic activity existed between the NL and HT control groups. These findings, together with those of others that relate chronic lung allograft dysfunction to an increase in BALF neutrophils and collagen matrix remodeling, collectively indicate that up-regulated proteolytic activity may have a role in chronic rejection after lung transplantation.
A Fast pH‐Switchable and Self‐Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium
Authors: Maartje M. C. Bastings, Stefan Koudstaal, Roxanne E. Kieltyka, Yoko Nakano, A. C. H. Pape, Dries A. M. Feyen, Frebus J. van Slochteren, Pieter A. Doevendans, Joost P. G. Sluijter, E. W. Meijer, Steven A. J. Chamuleau, Patricia Y. W. Dankers
Journal: Advanced Healthcare Materials (2013)

Abstract Minimally invasive intervention strategies after myocardial infarction use state‐of‐the‐art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH‐switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH &gt; 8.5, with a viscosity low enough to enable passage through a 1‐m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self‐healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.
Association Between Geographic Access to Cancer Care, Insurance, and Receipt of Chemotherapy: Geographic Distribution of Oncologists and Travel Distance
Authors: Chun Chieh Lin, Suanna S. Bruinooge, M. Kelsey Kirkwood, Christine Olsen, Ahmedin Jemal, Dean Bajorin, Sharon H. Giordano, Michael Goldstein, B. Ashleigh Guadagnolo, Michael Kosty, Shane Hopkins, James B. Yu, Anna Arnone, Amy Hanley, Stephanie Stevens, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2015)

Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy.Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics.Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P=.009) or ≥250 miles (OR, 0.36; P<.001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P=.77). When stratifying analyses by insurance status, non-privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P=.03).Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment.
Insulin-like growth factor 1 blocks collagen release and down regulates matrix metalloproteinase-1, -3, -8, and -13 mRNA expression in bovine nasal cartilage stimulated with oncostatin M in combination with interleukin 1alpha
Authors: W Hui
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To investigate the effect of insulin-like growth factor 1 (IGF1) on the release of collagen, and the production and expression of matrix metalloproteinases (MMPs) induced by the proinflammatory cytokine interleukin 1α (IL1α) in combination with oncostatin M (OSM) from bovine nasal cartilage and primary human articular chondrocytes. <h3>METHODS</h3> Human articular chondrocytes and bovine nasal cartilage were cultured with and without IGF1 in the presence of IL1α or IL1α + OSM. The release of collagen was measured by an assay for hydroxyproline. Collagenase activity was determined with the diffuse fibril assay using<sup>3</sup>H acetylated collagen. The expression of MMP-1, MMP-3, MMP-8, MMP-13, and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was analysed by northern blot. <h3>RESULTS</h3> IGF1 can partially inhibit the release of collagen induced by IL1α or IL1α + OSM from bovine nasal cartilage. This was accompanied by a reduced secretion and activation of collagenase by bovine nasal cartilage. IGF1 can also down regulate IL1α or IL1α + OSM induced MMP-1, MMP-3, MMP-8, and MMP-13 mRNA expression in human articular chondrocytes and bovine chondrocytes. It had no significant effect on the production and expression of TIMP-1 mRNA in chondrocytes. <h3>CONCLUSION</h3> This study shows for the first time that IGF1 can partially block the release of collagen from cartilage and suggests that down regulation of collagenases by IGF1 may be an important mechanism in preventing cartilage resorption initiated by proinflammatory cytokines.
A Method Using Induced Waves to Study Pressure Propagation in Human Arteries
Authors: MILTON LANDOWNE
Journal: Circulation Research (1957)

This report describes a method for utilizing externally induced impacts as a means of studying the propagation of pressure waves in intact human arteries. Because it is a new method its description is prefaced by a brief presentation of several factors relevant to wave propagation in living vessels; the description is followed by a critical evaluation.
Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome
Authors: Jessica Caprioli, Marina Noris, Simona Brioschi, Gaia Pianetti, Federica Castelletti, Paola Bettinaglio, Caterina Mele, Elena Bresin, Linda Cassis, Sara Gamba, Francesca Porrati, Sara Bucchioni, Giuseppe Monteferrante, Celia J. Fang, M. K. Liszewski, David Kavanagh, John P. Atkinson, Giuseppe Remuzzi
Journal: Blood (2006)
Breast Cancer Risk Following Bilateral Oophorectomy in <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers: An International Case-Control Study
Authors: Andrea Eisen, Jan Lubinski, Jan Klijn, Pal Moller, Henry T. Lynch, Kenneth Offit, Barbara Weber, Tim Rebbeck, Susan L. Neuhausen, Parviz Ghadirian, William D. Foulkes, Ruth Gershoni-Baruch, Eitan Friedman, Gadi Rennert, Teresa Wagner, Claudine Isaacs, Charmaine Kim-Sing, Peter Ainsworth, Ping Sun, Steven A. Narod
Journal: Journal of Clinical Oncology (2005)

The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery.We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use.A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57).Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies.
SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic Hormone-Sensitive Prostate Cancer
Authors: Evan Y. Yu, Hongli Li, Celestia S. Higano, Neeraj Agarwal, Sumanta K. Pal, Ajjai Alva, Elisabeth I. Heath, Elaine T. Lam, Shilpa Gupta, Michael B. Lilly, Yoshio Inoue, Kim N. Chi, Nicholas J. Vogelzang, David I. Quinn, Heather H. Cheng, Stephen R. Plymate, Maha Hussain, Catherine M. Tangen, Ian M. Thompson
Journal: Journal of Clinical Oncology (2015)

Purpose Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal immunoglobulin G 1 antibody that targets insulin-like growth factor I receptor (IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive prostate cancer xenograft model. Patients and Methods Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation (AD) to cixutumumab added to a luteinizing hormone–releasing hormone agonist with bicalutamide versus AD alone. With 180 patients and one-sided alpha of 0.10, there would be 90% power to detect an absolute 20% difference in undetectable prostate-specific antigen (PSA; ≤ 0.2 ng/mL) rate at 28 weeks (relative risk, 1.44); this end point was previously strongly correlated with survival. Secondary end points included the proportion of patients with PSA &gt; 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end point, and extended Mantel-Haenszel χ 2 test was used for three PSA response categories. Results The trial accrued 210 eligible patients (105 randomly assigned to each arm). Patient characteristics were similar in both arms. Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34 (32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower baseline CTCs (0 v 1 to 4 v ≥ 5/7.5 mL whole blood) were associated with higher rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF-IR biomarkers were not correlated with PSA outcome, and cixutumumab did not significantly change these biomarker levels. Conclusion Cixutumumab plus AD did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.
The Nature of Panic: A Walk Through Fear in Pictures and Words
Authors: Sabina Dosani
Journal: BMJ (2004)

An exhibition by Patrick Olszowski and Sophie Petit-Zeman, the.gallery@oxo, Oxo Tower Wharf, Bargehouse Street, London SE1 9PH, until 22 February 2004 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Fire. There's a fire and a woman is in there. Getting ready to go out. Meeting another man. Then a photographer leaps off a cliff. Is he out of his mind? You decide. The man is Patrick Olszowski and I am looking at two of his digitally enhanced images in this unusual exhibition. Olszowski has had panic attacks since his teens. Everyday happenings trigger terrifying changes to his inner world, yet Olszowski also claims that he remained unphased by a gale force seven in the Bay of Biscay. He is also a photographer who … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
How does B cell depletion therapy work, and how can it be improved?
Authors: E A Clark
Journal: Annals of the Rheumatic Diseases (2005)

The past few years have seen a surge of interest in B cell depletion therapy for patients with rheumatoid arthritis. This paper outlines the possible mechanism(s) by which B cell depletion therapy works. It is likely there is more than one mechanism and the relative importance of each mechanism depends on the target cell. These include CD20-induced apoptosis, complement dependent cytotoxicity, antibody dependent cell-mediated cytotoxicity, and selective targeting and depletion of B cell subsets. The implications of these mechanisms in the further improvement of B cell depletion therapy in rheumatoid arthritis and other autoimmune diseases are discussed.
Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor
Authors: Barbara Ukropcova, Michele McNeil, Olga Sereda, Lilian de Jonge, Hui Xie, George A. Bray, Steven R. Smith
Journal: Journal of Clinical Investigation (2005)

Metabolic flexibility of skeletal muscle, that is, the preference for fat oxidation (FOx) during fasting and for carbohydrate oxidation in response to insulin, is decreased during insulin resistance. The aim of this study was to test the hypothesis that the capacity of myotubes to oxidize fat in vitro reflects the donor's metabolic characteristics. Insulin sensitivity (IS) and metabolic flexibility of 16 healthy, young male subjects was determined by euglycemic hyperinsulinemic clamp. Muscle samples were obtained from vastus lateralis, cultured, and differentiated into myotubes. In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration). We termed these dynamic changes in FOx metabolic switching. In vivo, metabolic flexibility was positively correlated with IS and maximal oxygen uptake and inversely correlated with percent body fat. In vitro suppressibility was inversely correlated with IS and metabolic flexibility and positively correlated with body fat and fasting FFA levels. Adaptability was negatively associated with percent body fat and fasting insulin and positively correlated with IS and metabolic flexibility. The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.
The Derivation of Coronary Sinus Flow During Elevation of Right Ventricular Pressure
Authors: HERMAN M. GELLER, MARTIN BRANDFONBRENER, CARL J. WIGGERS
Journal: Circulation Research (1953)

The derivation of coronary sinus flow during increased pulmonary and right ventricular pressures was resubmitted to experimental study. The primary reduction and subsequent augmentation in coronary flow following pulmonary artery constriction and the persistence of a greater flow after release preclude the concept of a variable contribution via thebesian channels from the right ventricular cavity. When the magnitude of the increase is also considered, it is difficult to escape the conclusion that drainage from the right ventricle is also involved. The use of coronary sinus blood in studies of metabolism of the left ventricle under various dynamic conditions seems precarious.
Community-Based Intervention Research: Coping With the “Noise” of Real Life in Study Design
Authors: Ann A. Hohmann, M. Katherine Shear
Journal: American Journal of Psychiatry (2002)

The ultimate goal of clinical intervention research is to find a way to improve the care and lives of people suffering from specific psychiatric symptoms, illnesses, and/or disabilities. This article provides to clinical researchers a set of issues to consider and steps to follow in making the transition to more public-health-oriented, community-based research. Traditional, academically based, randomized clinical trials test an intervention against a placebo or alternate treatment control condition, focusing on a single, specific main outcome. Community-based intervention trials also test a treatment intervention but in the context of the community environment. These trials, in order to provide meaningful information for community clinical practice, must take into account many factors that are controlled or are not considered in traditional clinical trials. Investigators need to be clear about the goal of community-based interventions; they need to determine the social and cultural norms, expectations, and conflicts of the community and of the setting, and they need to work collaboratively with experts in both qualitative and quantitative design.
Acute vasodilator testing in idiopathic pulmonary arterial hypertension: must we take NO for the answer?
Authors: C. F. Opitz, L. J. Rubin
Journal: European Respiratory Journal (2009)

The earliest clinical descriptions of primary pulmonary hypertension, now known as idiopathic pulmonary arterial hypertension (IPAH), were accompanied by the hypothesis that pulmonary vasoconstriction was one of its key pathophysiological elements 1 and that vasodilators could, therefore, be therapeutically useful. In support of this concept, Dresdale et al. 2 first reported attenuation of pulmonary hypertension with the systemic vasodilator tolazoline, while Harris 3 and Wood et al. 4 achieved more preferential pulmonary vasodilation with acetylcholine infused directly in the pulmonary artery. Only years later, when Furchgott and Zawadzki 5 demonstrated that acetylcholine-induced vasodilation was mediated by nitric oxide (NO), an observation for which R.F. Furchgott shared the Nobel Prize in Medicine in 1998, was the importance of endothelial dysfunction in the pathogenesis of IPAH appreciated, and the rationale for testing acute vasoreactivity in IPAH using inhaled NO (iNO) or other endothelial-derived vasodilator substances established.

When Rich and Brundage 6 treated patients with high-dose calcium channel blockers (CCBs) in an attempt to reverse pulmonary vasoconstriction it became clear, however, that only a subgroup of IPAH patients responded with haemodynamic and clinical improvement. Furthermore, since it was impossible to identify a priori any clinical or haemodynamic predictors for a positive responder status, nonresponders were subjected both acutely and chronically to the risks of potent systemic vasodilator agents without any chance of benefit. Additionally, the criteria for “acute response” that was predictive of at least a reasonable chance of achieving a favourable long-term response to treatment with CCB was not clear …