tbuckley/cabot-search huggingface dataset:
Money and Distorted Ethical Judgments about Research: Ethical Assessment of the TeGenero TGN1412 Trial
Authors: Ezekiel J. Emanuel, Franklin G. Miller
Journal: The American Journal of Bioethics (2007)

Abstract The recent TeGenero phase I trial of a novel monoclonal antibody in healthy volunteers produced a drastic inflammatory reaction in participants receiving the experimental agent. Commentators on the ethics of the research have focused considerable attention on the role of financial considerations: the for-profit status of the biotechnology company and Contract Research Organization responsible respectively for sponsoring and conducting the trial and the amount of monetary compensation to participants. We argue that these financial considerations are largely irrelevant and distort ethical appraisal of this tragic research. Except for administering the antibody to all 6 participants nearly simultaneously, the trial appears to fulfill all of the critical ethical requirements for clinical research—social value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for enrolled participants. Disclaimer: The ideas and opinions expressed are the authors' views. They do not represent any position or policy of the National Institutes of Health, Public Health Service, or Department of Health and Human Services. Neither author owns any stock in any pharmaceutical, biotechnology, or CRO company. Neither author has consulted or received an honorarium from any pharmaceutical, biotechnology, or CRO company in the last 3 years.
Systematic Population-Based Assessment of Cancer Risk in First-Degree Relatives of Cancer Probands
Authors: D E Goldgar, D F Easton, L A Cannon-Albright, M H Skolnick
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Systematic Population-Based Assessment of Cancer Risk in First-Degree Relatives of Cancer Probands Get access David. E. Goldgar, David. E. Goldgar Search for other works by this author on: Oxford Academic PubMed Google Scholar Douglas. F. Easton, Douglas. F. Easton Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa. A. Cannon-Albright, Lisa. A. Cannon-Albright Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark H. Skolnick Mark H. Skolnick Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 21, 2 November 1994, Pages 1600–1608, https://doi.org/10.1093/jnci/86.21.1600 Published: 02 November 1994 Article history Received: 29 March 1994 Revision received: 08 August 1994 Accepted: 11 August 1994 Published: 02 November 1994
Impact of Clinical Reactions on IgE Concentrations to Egg, Milk and Peanut in the Observational Cohort of the Consortium for Food Allergy Research (COFAR)
Authors: Scott H. Sicherer, Robert A. Wood, Stacie M. Jones, Tamara T. Perry, Brian P. Vickery, A. Wesley Burks, Andrew H. Liu, Donald Y.M. Leung, Robert W. Lindblad, Peter Dawson, Beth Blackwell, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2015)
A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis
Authors: Edith Villeneuve, Jackie L Nam, Mary J Bell, Christopher M Deighton, David T Felson, Johanna M Hazes, Iain B McInnes, Alan J Silman, Daniel H Solomon, Andrew E Thompson, Patience H P White, Vivian P Bykerk, Paul Emery
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. <h3>Objective</h3> To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. <h3>Methods</h3> The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007–2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. <h3>Results</h3> (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. <h3>Conclusions</h3> This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.
American Society of Clinical Oncology Clinical Practice Guidelines: Formal Systematic Review–Based Consensus Methodology
Authors: D. Andrew Loblaw, Ann Alexis Prestrud, Mark R. Somerfield, Thomas K. Oliver, Melissa C. Brouwers, Robert K. Nam, Gary H. Lyman, Ethan Basch
Journal: Journal of Clinical Oncology (2012)

The American Society of Clinical Oncology (ASCO) guidelines program employs a systematic review-based methodology to produce evidence-based guidelines. This is consistent with the stance of the Institute of Medicine on guideline development, which is that high-quality evidence syntheses form the basis for recommendation development. In the absence of high-quality evidence, recommendation development becomes more complex. One option is to provide no recommendations or withdraw a guideline topic. However, it is often the areas of greatest uncertainty in which the evidentiary base is incomplete, and thus, guidelines are needed most. To provide recommendations in such circumstances, an explicit methodology is needed to ensure that a credible process is undertaken, and rigorous, reliable advice is provided. In 2010, the ASCO Board of Directors approved development of guideline recommendations using consensus methodology. A modified Delphi approach to recommendation development, based on the best available data identified in a systematic review, was piloted with an ASCO guideline. Consensus was achieved through the rating of a series of recommendations by a large group of clinicians, including academic and community-based content and methodology experts. A prespecified threshold of agreement was determined to indicate when consensus was achieved. Consensus was defined as agreement by ≥ 75% of raters. The formal consensus methodology used by ASCO enabled development of guideline recommendations on a challenging clinical issue based on limited evidence using a rigorous, transparent, and explicit method. This methodology is proposed for development of future ASCO guidelines on topics for which limited evidence is available.
FGFR3-targeted mAb therapy for bladder cancer and multiple myeloma
Authors: Yaron Hadari, Joseph Schlessinger
Journal: Journal of Clinical Investigation (2009)

Gain-of-function mutations in FGF receptor 3 (FGFR3) have been implicated in severe skeletal dysplasias and in a variety of cancers. In their study in this issue of the JCI, Qing et al. used specific shRNA probes to demonstrate that FGFR3 functions as an important driver of bladder carcinoma cell proliferation (see the related article beginning on page 1216). A unique anti-FGFR3 mAb was shown to exhibit antitumor activity in human bladder carcinoma cells in vitro and in mouse bladder cancer or multiple myeloma xenograft tumor models bearing either wild-type or mutant FGFR3. These results suggest that clinical development of anti-FGFR3 mAbs should be considered for targeted therapy of cancer and other diseases.
Posttranscriptional Compensation for Heterozygous Disruption of the Kidney-Specific NaK2Cl Cotransporter Gene
Authors: Nobuyuki Takahashi, Heddwen L. Brooks, James B. Wade, Wen Liu, Yoshiaki Kondo, Sadayoshi Ito, Mark A. Knepper, Oliver Smithies
Journal: Journal of the American Society of Nephrology (2002)

Mice homozygous for a loss of function mutation of the kidney-specific NaK2Cl cotransporter, BSC1/NKCC2, do not survive. Here the effects of loss of one copy of the gene are studied. NKCC2 mRNA of NKCC2 +/- kidney was 55 +/- 6% of +/+, yet no differences were found between NKCC2 +/+ and +/- mice in BP, blood gas, electrolytes, creatinine, plasma renin concentration, urine volume and osmolality, ability to concentrate and dilute urine, and response to furosemide. When mice were challenged with 180 mM NH(4)Cl, plasma ammonia and urinary ammonia excretion were increased twofold and fivefold, respectively, but there was still no difference between the two genotypes. NKCC2 +/- mice had a near-normal level of NKCC2 protein and no clear change in the distribution of NKCC2 in the thick ascending limb (TAL) cells. In vitro microperfusion of isolated TAL showed no significant difference between the two genotypes in the basal and vasopressin-stimulated capacity to reabsorb NaCl. There was no difference in the mRNA expressions of thiazide-sensitive NaCl cotransporter, epithelial Na channel (ENaC), aquaporin-2, ROMK, and NaKATPase. Halving the mRNA expression of NKCC2 does not affect BP or fluid balance because of compensatory factors that restore the protein level to near normal. One possible factor is a regulated increase in the movement of cytoplasmic protein to the luminal membrane leading to a restoration of functional transporter to an essentially wild type level.
The epidemiology of sleep apnoea.
Authors: R J Davies, J R Stradling
Journal: Thorax (1996)

We conducted a study of the prevalence of sleep-disordered breathing in subjects derived from a random sample of the population.A total of 2,202 subjects 35 to 69yr of age were approached.Four hundred forty-one answered a questionnaire concerning their sleep symptoms, general health, and habits such as alcohol consumption, and they were monitored for sleep-disordered breathing (SDB).The sample was biased in favor of snorers and those with other subjective sleep complaints.Fifty-six percent of the subjects were men.Of the 441 subjects 79 (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory distress index [RDI] > 15), 289 were snorers but had RDI <15, and 73 were nonsnorers.The prevalence of SDB in this sample was therefore at least 3.6% (79 of Z,204).The minimum prevalence in men was 5.7%, and in women it was 1.2%.Logistic regression identified only male sex as an independent predictor of snoring without SDB (adjusted odds ratio [OR], 3-24; 95% Cl, 1-33 to 7.82), body mass index (adjusted OR for an increase of 5 kg/iM2, 0-95; 95% Cl, 0 85 to 1.05), and alcohol consumption (adjusted OR for an increase of 10 g/day, 1 05; 95% Cl, 0*84 to 1.37) were not significant predictors of snoring.The independent predictors of SDB among snorers were age (adjusted OR for an increase of 5yr, 1 26; 95% Cl, 1 08 to 1.47) and neck circumference (adjusted OR for an increase of 2 cm, 1-53; 95% Cl, 1 16 to 2.00).Alcohol consumption was not a factor (adjusted OR for an increase of lOgIday, 0 98; 95% Cl, 086 to 1.12).
Chronic ethanol administration impairs receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes
Authors: Douglas D. Dalke, Michael F. Sorrell, Carol A. Casey, Dean J. Tuma
Journal: Hepatology (1990)

The effects of chronic ethanol administration on the receptor-mediated endocytosis of epidermal growth factor were studied in isolated rat hepatocytes. In initial experiments, it was demonstrated that significantly less ligand was bound by hepatocytes isolated from rats fed an ethanol liquid diet for 5 to 7 wk than by cells isolated from chow-fed or pair-fed controls. Reduced binding was shown to be primarily caused by a decreased number of surface receptors rather than by changes in receptor affinity. When hepatocytes were incubated at 37° C in the presence of a large saturating concentration of epidermal growth factor (80 nmol/L), intracellular levels of the ligand were significantly lower in cells from the ethanol-fed animals. However, no effect on degradation of the ligand was observed under those conditions. A defect in the initial stages of receptor-ligand internalization was also indicated because less surface-bound ligand was internalized and subsequently degraded in cells from the ethanoltreated rats. When the endocytosis of a lower, more physiological concentration of the growth factor (0.5 nmol/L) was studied, both the uptake of ligand and its degradation were markedly impaired in hepatocytes from the ethanol-fed animals. These results indicate that chronic ethanol administration impairs the receptor-mediated endocytosis of epidermal growth factor by the liver. The major impairment appears to be a reduction of cell surface receptors; however, other steps of the endocytotic pathway also appear to be affected. These altered steps include defective receptor-ligand internalization and changes in intracellular processing of the ligand leading to decreased degradation. (HEPATOLOGY 1990;12:1085–1091).
Inhibition of Connective Tissue Growth Factor (CTGF/CCN2) Expression Decreases the Survival and Myogenic Differentiation of Human Rhabdomyosarcoma Cells
Authors: Stefania Croci, Lorena Landuzzi, Annalisa Astolfi, Giordano Nicoletti, Angelo Rosolen, Francesca Sartori, Matilde Y. Follo, Noelynn Oliver, Carla De Giovanni, Patrizia Nanni, Pier-Luigi Lollini
Journal: Cancer Research (2004)

Abstract Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.
Infection and inflammation and the coagulation system
Authors: M Levi
Journal: Cardiovascular Research (2003)

Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). Systemic inflammation results in activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Pro-inflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice-versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the promising results in the treatment of severe systemic infection with modulators of coagulation and inflammation.
SPONTANEOUS RUPTURE OF THE RIGHT VENTRICLE OF THE HEART
Authors: B. L. Hodge
Journal: BMJ (1927)

be paid to the fitting of a suitable shoe that is not too short.Measures must also be takeni for the treatment of a ten'dency to faulty statics and flat-foot, which it is usual to find associated with hballux rigidus, and which are concerned in its causation.
Re: Adverse Effect on Bone Marrow Protection of Prechemotherapy Granulocyte Colony-Stimulating Factor Support
Authors: A. Ribas, J. Albanell, L.-A. Sole-Calvo, J. Bellmunt
Journal: JNCI Journal of the National Cancer Institute (1997)

Increased proliferation of endogenous bone marrow progenitor cells in response to the administration of hematopoietic growth factors, followed by reduced cell cycling or entrance of the cells into a quiescent state upon withdrawal of the growth factors, may have clinically relevant effects on the tolerance of the hematopoietic system to subsequent myelotoxic treatments.We investigated the ability of granulocyte colony-stimulating factor (G-CSF) to protect progenitor cells in the bone marrow of cancer patients from the toxic effects of subsequent treatments with chemotherapeutic agents.Thirty-six patients with histologically documented, locally advanced or metastatic breast cancer were randomly assigned to receive doxorubicin once every 3 weeks at a dose of 75 mg/m2 and cyclophosphamide at a dose of 1000 mg/m2, with G-CSF administered either before and after chemotherapy (18 patients) or after chemotherapy only (18 patients). For prechemotherapy administration of G-CSF, recombinant human methionyl (r-met Hu) G-CSF was administered subcutaneously to patients twice per day for 5 days at a dose of 5 micrograms/kg, with the last dose given 48 hours before the start of chemotherapy. For postchemotherapy administration of G-CSF, r-met Hu G-CSF was administered subcutaneously to patients once per day for 7 days at a dose of 5 micrograms/kg, with the first dose given 24 hours after chemotherapy.The incidence or the duration of grade 4 neutropenia was not reduced in all patients by the use of prechemotherapy G-CSF; the incidence over all cycles of chemotherapy was 74% for patients treated with prechemotherapy and postchemotherapy G-CSF and 66% for patients treated with postchemotherapy G-CSF only (two-sided P, adjusted for dose = .21) and the median duration in both treatment arms was 3 days (two-sided P = .19). Unexpectedly, the incidence of grades 3 and 4 thrombocytopenia was much greater in patients who received prechemotherapy G-CSF compared with those who did not (54% versus 6%, respectively, over all chemotherapy cycles; two-sided P, adjusted for dose < .001). No difference in the decrease in hemoglobin level (adjusted for red blood cell transfusions) between patients in the two treatment arms was observed.No beneficial effects were associated with the administration of G-CSF to cancer patients prior to chemotherapy. The observation of more severe thrombocytopenia in patients treated with prechemotherapy G-CSF led us to conclude that the proliferation of progenitor cells was still increased 48 hours after the last dose of G-CSF and that the administration of chemotherapy at or within this time period actually worsens the toxic effects on bone marrow. This result has important ramifications for the design of clinical cancer treatment protocols, especially those that involve shortened intervals between cycles of chemotherapeutic agent administration.
Removal of a dental post from the bronchus by interventional cardiovascular techniques.
Authors: J S Gibbs, L J Murdoch, P Goldstraw, N P Buller
Journal: Thorax (1994)

Foreign bodies lodged in the bronchial tree are normally retrieved by bronchoscopy, but if this fails then thoracotomy is necessary. The case history is presented of a patient who had inhaled a dental post which could not be retrieved either by flexible or rigid bronchoscopy. Using biplane screening and intravascular retrieval devices introduced via an endotracheal tube, the dental post was removed successfully without the need for thoracotomy.
Group I Intron–Mediated Trans-splicing in Mitochondria of Gigaspora rosea and a Robust Phylogenetic Affiliation of Arbuscular Mycorrhizal Fungi with Mortierellales
Authors: Maryam Nadimi, Denis Beaudet, Lise Forget, Mohamed Hijri, B. Franz Lang
Journal: Molecular Biology and Evolution (2012)

Gigaspora rosea is a member of the arbuscular mycorrhizal fungi (AMF; Glomeromycota) and a distant relative of Glomus species that are beneficial to plant growth. To allow for a better understanding of Glomeromycota, we have sequenced the mitochondrial DNA of G. rosea. A comparison with Glomus mitochondrial genomes reveals that Glomeromycota undergo insertion and loss of mitochondrial plasmid-related sequences and exhibit considerable variation in introns. The gene order between the two species is almost completely reshuffled. Furthermore, Gigaspora has fragmented cox1 and rns genes, and an unorthodox initiator tRNA that is tailored to decoding frequent UUG initiation codons. For the fragmented cox1 gene, we provide evidence that its RNA is joined via group I–mediated trans-splicing, whereas rns RNA remains in pieces. According to our model, the two cox1 precursor RNA pieces are brought together by flanking cox1 exon sequences that form a group I intron structure, potentially in conjunction with the nad5 intron 3 sequence. Finally, we present analyses that address the controversial phylogenetic association of Glomeromycota within fungi. According to our results, Glomeromycota are not a separate group of paraphyletic zygomycetes but branch together with Mortierellales, potentially also Harpellales.
Severe ear chondritis due to cowpox virus transmitted by a pet rat
Authors: Antoine Elsendoorn, Gérard Agius, Gwenaël Le Moal, Fouad Aajaji, Anne-Laure Favier, Ewa Wierzbicka-Hainault, Guillaume Béraud, Olivier Flusin, Jean-Marc Crance, France Roblot
Journal: Journal of Infection (2011)