tbuckley/cabot-search huggingface dataset:
The Staphylococcus aureus “superbug”
Authors: Timothy J. Foster
Journal: Journal of Clinical Investigation (2004)

There has been some debate about the disease-invoking potential of Staphylococcus aureus strains and whether invasive disease is associated with particularly virulent genotypes, or "superbugs." A study in this issue of the JCI describes the genotyping of a large collection of nonclinical, commensal S. aureus strains from healthy individuals in a Dutch population. Extensive study of their genetic relatedness by amplified restriction fragment typing and comparison with strains that are associated with different types of infections revealed that the S. aureus population is clonal and that some strains have enhanced virulence. This is discussed in the context of growing interest in the mechanisms of bacterial colonization, antibiotic resistance, and novel vaccines.
Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Corey J. Langer, Silvia Novello, Keunchil Park, Maciej Krzakowski, Daniel D. Karp, Tony Mok, Rebecca J. Benner, Judith R. Scranton, Anthony J. Olszanski, Jacek Jassem
Journal: Journal of Clinical Oncology (2014)

Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC).
VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials
Authors: Diether Lambrechts, Bart Claes, Paul Delmar, Joke Reumers, Massimiliano Mazzone, Betül T Yesilyurt, Roland Devlieger, Chris Verslype, Sabine Tejpar, Hans Wildiers, Sanne de Haas, Peter Carmeliet, Stefan J Scherer, Eric Van Cutsem
Journal: The Lancet Oncology (2012)
Multiple nodular pulmonary amyloidosis. A case report and comparison with diffuse alveolar-septal pulmonary amyloidosis.
Authors: S C Lee, H Johnson
Journal: Thorax (1975)

A case of multiple nodular pulmonary amyloidosis in a 54-year-old Caucasian man is presented. Discrete symptomless radiodensities had developed in this patient's lungs within a period of three years, leading to a suspicion of a neoplastic process. The amyloid nature of these nodules was demonstrated by biopsy. In this case, as in others previously reported, there was no evidence of systemic disease, and immunoglobulins were normal. Local factors probably play an important part in the pathogenesis of this disease. This entity is to be distinguished from the diffuse type of pulmonary amyloidosis, which has a far graver prognosis. Diffuse alveolar septal amyloidosis is usually associated with primary systemic amyloidosis or multiple myeloma and leads rapidly to respiratory distress.
Magnetic resonance imaging of the spine and the sacroiliac joints in ankylosing spondylitis and undifferentiated spondyloarthritis during treatment with etanercept
Authors: M Rudwaleit
Journal: Annals of the Rheumatic Diseases (2005)

To assess the changes in inflammatory lesions of the spine and the sacroiliac (SI) joints as detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) with predominant axial symptoms during treatment with etanercept.MRI of the spine and/or the SI joints of patients with active AS or axial uSpA was performed at baseline (TP0, n = 25), after 6 weeks (TP1, n = 20), and after 24 weeks of continuous treatment with etanercept (TP2, n = 12). T1 weighted spin echo pre -(T1), post-gadolinium (T1/Gd-DTPA) and short tau inversion recovery (STIR) MRI sequences were used to assess chronic and active spinal lesions using the scoring system ASspiMRI. Active and chronic SI lesions were assessed using a simple scoring system.By use of the definite STIR sequence, significant regression of spinal inflammation was already seen already after 6 weeks in the patients treated with etanercept (mean (SD) 11.2 (13.8) at TP0 v 6.8 (7.9) at TP1; p = 0.023) but not in patients treated with placebo. Continuous treatment with etanercept for 24 weeks reduced active spinal changes by 69% (p = 0.012). T1/Gd-DTPA sequences gave similar results. There was only a trend for a decrease of active inflammatory lesions of the SI joints.Etanercept treatment in patients with active AS and uSpA leads to regression of active inflammatory lesions of the spine as depicted by MRI. The potential role of etanercept on deceleration of chronic spinal changes needs further study.
Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study
Authors: Anna R Giuliano, Ji-Hyun Lee, William Fulp, Luisa L Villa, Eduardo Lazcano, Mary R Papenfuss, Martha Abrahamsen, Jorge Salmeron, Gabriella M Anic, Dana E Rollison, Danelle Smith
Journal: The Lancet (2011)
Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression
Authors: Heidi Schwarzenbach, Corinna Eichelser, Jolanthe Kropidlowski, Wolfgang Janni, Brigitte Rack, Klaus Pantel
Journal: Clinical Cancer Research (2012)

Abstract Purpose: LOH on circulating DNA may provide tumor-specific information on breast cancer. As identification of LOH on cell-free DNA is impeded by the prevalence of wild type DNA in blood of cancer patients, we fractionated plasma DNA, and determined the diagnostic and prognostic value of both fractions. Experimental design: Our cohort of 388 patients with primary breast cancer before chemotherapy was selected from a multicenter study (SUCCESS). Postoperative plasma was fractionated in low- and high-molecular weight DNA by two different column systems. In both fractions, LOH was determined by a PCR-based microsatellite analysis using a panel of 8 polymorphic markers. Circulating tumor DNA in plasma from 30 patients after chemotherapy was additionally analyzed. The significance levels were adjusted for multiple comparisons. Results: More patients (38%) had LOH at all markers in the fraction containing short DNA fragments than in the fraction containing the long DNA molecules (28%, P = 0.0001). In both fractions 32.85% of LOH were concordant. LOH at the markers D3S1605, D10S1765, D12S1725, D13S218, and D17S855 significantly correlated with tumor stage, tumor size, and lymph node metastasis, positive progesterone, and HER2 receptor status. Most importantly, LOH at D12S1725 mapping to cyclin D2 correlated with shorter overall survival (P = 0.004). Conclusions: The improved detection of LOH on cell-free DNA provides important information on DNA losses of tumor suppressor genes TIG1, PTEN, cyclin D2, RB1, and BRCA1 in breast cancer. In particular, loss of the cyclin D2 gene might become an important prognostic marker easily detectable in the peripheral blood. Clin Cancer Res; 18(20); 5719–30. ©2012 AACR.
Insulin-Like Growth Factor-I Produced by Seminal Vesicles: Relationship to Intraepithelial Basal Cell Hyperplasia in the Prostate
Authors: Fernando U. Garcia, Katarzyna Urbanska, Lauren Koltowski, Krzysztof Reiss, Christian Sell
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study examined the seminal vesicle fluid (SVF) as a potential local source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the prostate. Experimental Design: IGF-I levels in seminal fluid were measured. The levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well as direct downstream targets were examined in the peripheral zone of the prostate. Results: In situ, we find that the IGF-IR is activated in the peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and cancer. In addition, immunostaining reveals preferential activation of the IGF-IR in p63-positive cells in areas of intermediate basal cell hyperplasia in the peripheral zone, indicating that prostate progenitor cells are highly sensitive to increases in local IGF-I levels. These areas of basal cell hyperplasia occur at high incidence in the peripheral zone of the prostate. Relatively high levels of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the proliferation of both normal and cancer-derived prostate cells. Conclusions: These results suggest that SVF is a local source of IGF-I that provides chronic stimulation of prostate cells. This chronic stimulation could contribute to the development of prostate cancer in older men.
Disseminated Sclerosis: The Rat as a Possible Carrier of Infection
Authors: I. G. H. Wilson
Journal: BMJ (1927)

_'9"2']LETHARGOIC ElN-PHAtiItIS VR AIttlY lY" ULTRA.VIOLET RAYS.~TBim It ~~~~~~~~~~~~~~~~~~~~~~~~~~MEDI The entire body (back and front) has been exposed to r-adia- tions from a mercury vapour lamp (or prefeiably to the rays of three of these lamps used simultaneously) twice weekly for a period of six to seven weeks, the maximum exposuire being ten miniutes to both back and Ifronit of the body, at a distance of about 16 inches from the burner.
Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies
Authors: G. Spinetti, N. Kraenkel, C. Emanueli, P. Madeddu
Journal: Cardiovascular Research (2008)

Over the past two decades, extensive research has focused on arterial remodelling in both physiological and pathological ageing. The concept now describes the growth as well as the rearrangement of cellular components and extracellular matrix, resulting in either reduction or increase in vessel lumen. In diabetes, remodelling extends to capillaries, microvascular beds, and arteries of different calibre. This process is paralleled by accelerated atherosclerosis and accounts for an increased incidence of ischaemic complications. The incapacity of pre-existing and de novo formed collaterals to bypass atherosclerotic occlusions, combined with a decline in tissue capillary density, is responsible for the delayed recovery from ischaemia and ultimately leads to organ failure. The mechanisms of vascular remodelling are incompletely understood, but metabolic and mechanical factors seem to play an important role. Hyperglycaemia represents the main factor responsible for the fast progression of atherosclerosis as well as microangiopathy. However, intensive blood glucose control alone is insufficient to reduce the risk of macrovascular complications. Pharmacological control of oxidative stress and stimulation of nitric oxide release have proved to exert beneficial effects on vascular remodelling in experimental diabetic models. New approaches of regenerative medicine using vascular progenitor cells for the treatment of ischaemic disease have been shown to be safe and are now being tested for efficacy in pre-clinical and clinical trials.
Etiology of extubation failure and the predictive value of the rapid shallow breathing index.
Authors: S K Epstein
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Failure of weaning from mechanical ventilation is thought to result from an imbalance between respiratory muscle capacity and respiratory demand. The ratio of respiratory rate to tidal volume (f/VT, rapid shallow breathing index) during spontaneous unsupported respiration increases when this imbalance exists, and may predict the success or failure of weaning from mechanical ventilation. Using f/VT, Yang and Tobin demonstrated a positive predictive value (PPV) of 0.78 (f/VT < or = 105 and weaning success) (1). To define the etiology of the 20% false-positive rate (FPR, f/VT < or = 105 and weaning failure), 94 patients who had an f/VT determined prior to extubation were studied prospectively. Of 84 patients with an f/VT < 100, 14 required reintubation within 72 h of extubation (FPR = 0.17, PPV = 0.83). Extubation in 13 of these 14 cases failed because of congestive heart failure, upper airway obstruction, aspiration, encephalopathy, or the development of a new pulmonary process. Only one patient needed reintubation solely because of the original respiratory process. Of 10 patients extubated with an f/VT > or = 100, four required reintubation, all because of the underlying respiratory process. This study confirms the high PPV for an f/VT < 100. The FPR of approximately 0.20 is best explained by extubation failure caused by processes for which f/VT is physiologically or temporally unlikely to predict success or failure. The negative predictive value (f/VT > or = 100 but extubation success) for f/VT may be lower than previously reported.
Game theory can build higher mental processes from lower ones<sup>1</sup>
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2007)

The question of reductionism is an obstacle to unification. Many behavioral scientists who study the more complex or higher mental functions avoid regarding them as selected by motivation. Game-theoretic models in which complex processes grow from the strategic interaction of elementary reward-seeking processes can overcome the mechanical feel of earlier reward-based models. Three examples are briefly described.
STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH)
Authors: E. Weston Hurst
Journal: The Journal of Experimental Medicine (1934)

After intramuscular, intradermal and subcutaneous inoculation, the pseudorabies virus reaches the central nervous system by way of the peripheral nerves, although it is circulating in the blood. Centrifugal spread from the infected nervous tissues by the neural route also occurs. After intracerebral inoculation the virus passes in the reverse direction, down the nervous axis. The Aujeszky strain invades the blood stream more readily than does the Iowa strain; but possibly with repeated passage the latter is approximating in this respect more closely the classical Aujeszky strain. After intravenous inoculation, effective with even small doses, virus is rapidly removed from the blood, and multiple infective foci are established in various organs; thence ascent of the virus by the peripheral nerves leads to infection of the central nervous system, the symptomatology differing according to whether the spinal cord or the medulla is first reached. The lack of evidence that the virus can penetrate directly the hemato-encephalic barrier deserves emphasis. When subcutaneous inoculation is practised in an area deprived of its nerve supply, the ability of the virus to invade the blood stream permits it to establish infective foci in the various viscera, and, after a predictable delay, the course of infection resembles that following intravenous injection. The pseudorabies virus is pantropic; i.e., it readily attacks cells derived from any embryonic layer. Lesions in the adrenal gland following intravenous inoculation are very like those due to herpes virus similarly introduced, this being one point of similarity in the pathogenic action of the two organisms. The relation of the pseudorabies virus to other viruses affecting the central nervous system is discussed.
Studies on Prostatic Cancer. I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate
Authors: Charles Huggins, Clarence V. Hodges
Journal: Cancer Research (1941)

Carcinoma of the prostate gland is peculiarly favorable for endocrine investigation since frequent serial observations of the activity of phosphatases in serum were found to provide objective indices of activity of the neo/~i~m when the enzymes were increased in amount above normal. In the present paper data are given for the values of serum phosphatases in carcinoma of the prostate and in normal men. We shall demonstrate that the   of serum is reduced in metastatic carcinoma of the prostate by decreasing the activity of androgens through castration or estrogenic injections and that this enzyme is increased by injecting androgens. We have been unable to find previous observations indicating any relationship of hormones to carcinoma of the prostate gland. An enzyme capable of hydrolyzing phosphoric esters was discovered by Grosser and Husler (4) in intestinal mucosa and kidney. Robison (16) found that this enzyme was particularly high in activity in growing bone and cartilage and that its activity was greatest at pH 9 to 9.5. This ~alkaline  was found by Kay (9) to be increased in the serum in certain bone diseases including metastasis of neoplasms to bone and later work has shown that among these conditions is carcinoma of the prostate. Davies (3) and Bamann and Riedel (1) discovered that there occurs in the spleen and kidney of swine and cattle, in addition to the alkaline phosphatase, a  with an activity maximum at pH 4.8. An enzyme believed to be identical with this acid phosphatase was found by Kutscher and Wolbergs (11) to be present in very large amount in the human prostate gland. This finding of great activity of   in the prostate gland was confirmed and extended to include prostatic cancer by Gutman, Sproul, and Gutman (7). The serum of certain patients with disseminated prostatic carcinoma was found by Gutman and Gutman (6) and Barringer and Woodard (2) to exhibit increased   activity. Robinson, Gutman, and Gutman'~I5) summarized the   activity levels of 44 patients with carcinoma of the prostate. They concluded that a marked rise in   in serum is associated with the appearance or spread of roentgenologically demonstrable skeletal metastases and implies dissemination of the primary tumor and thus is of unfavorable prognostic significance. METttODS AND MATERIALS
TCT-58 Effects of Mechanical Thrombectomy and Intracoronary Abciximab on Coronary Flow and Infarct Size During Primary PCI: Analysis from the INFUSE-AMI Trial
Authors: Jan-Henk Dambrink, Sorin Brener, Akiko Maehara, Saquib Chowdhary, Anthony Gershlick, Jacques Koolen, Roxana Mehran, Martin Fahy, C. Michael Gibson, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)
Postischemic Gene Transfer of Interleukin-10 Protects Against Both Focal and Global Brain Ischemia
Authors: Hiroaki Ooboshi, Setsuro Ibayashi, Takashi Shichita, Yasuhiro Kumai, Junichi Takada, Tetsuro Ago, Shuji Arakawa, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Mitsuo Iida
Journal: Circulation (2005)

Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia.Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or beta-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1beta, or tissue necrosis factor-alpha in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623+/-2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1beta and augmented tissue necrosis factor-alpha.Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.
Role and Relevance of Neurocognitive Assessment in Clinical Trials of Patients With CNS Tumors
Authors: Christina A. Meyers, Paul D. Brown
Journal: Journal of Clinical Oncology (2006)

The inclusion of neurocognitive end points in clinical trials of patients with CNS tumors is increasing. Neurocognitive end points are used to understand what cognitive problems exist before treatment to establish a baseline by which the effect of treatment is judged, and to determine whether different treatment regimens improve neurocognitive function due to better tumor control, slow expected neurocognitive deterioration due to the tumor, or have more or less short- and long-term neurotoxicity. However, the use of neurocognitive end points in clinical trials for patients with CNS tumors is in its infancy, so that long-term outcomes are difficult to predict and the ability to determine the effects of different agents and treatment approaches is scant. Including this aspect of patient evaluation in addition to survival and time to tumor progression will yield better risk-versus-benefit assessments as well as provide a basis for improving interventions.
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study
Authors: Robert P Giugliano, Nihar R Desai, Payal Kohli, William J Rogers, Ransi Somaratne, Fannie Huang, Thomas Liu, Satishkumar Mohanavelu, Elaine B Hoffman, Shannon T McDonald, Timothy E Abrahamsen, Scott M Wasserman, Robert Scott, Marc S Sabatine
Journal: The Lancet (2012)
Periodontal considerations in restorative and implant therapy
Authors: Perry V. Goldberg, Frank L. Higginbottom, Thomas G. Wilson
Journal: Periodontology 2000 (2001)

The successful integration of periodontal and restorative dentistry for both natural teeth and implants requires knowledge and application of both mechanical and biological principles. In areas of aesthetic concern, an adequate band of attached gingiva can increase patient comfort, reduce the probability of gingival recession following tooth preparation and simplify restorative procedures. While some restorative margins need to be placed at or below the margin of the free gingiva, this should be considered to be a compromise, and margins should not be placed more than 0.5 mm into a healthy gingival sulcus. Approximately 2-3 mm of healthy, natural supra-alveolar tooth surface is needed for attachment of the gingival tissues to the tooth. This dimension is called the biological width. If adequate biological width does not exist, surgical or orthodontic procedures to expose healthy tooth structure are recommended before final restorations are placed. Retraction of soft tissues for impressions is best accomplished with mechanical methods rather than lasers or electrosurgery because of the potentially harmful effects of these devices to the cementum, bone and soft tissues surrounding the teeth. Implants function best and withstand occlusal forces optimally when loaded in a vertical direction. Therefore, planning implant placement is critical for success. Because of increased proprioception, it is suggested that natural teeth be used to guide the occlusion in partially edentulous patients. Cantilevers should be used with caution and with appropriate attention to occlusal forces. While occlusal trauma does not cause periodontal disease, it may contribute to bone loss around teeth and implants. In the opinion of the authors, provisional restorations are an integral part of dental and periodontal therapy. They can be used to establish aesthetic and physiological contours that can be easily cleaned by patients and they can also be used as a guide for any needed surgical tissue modification.