tbuckley/cabot-search huggingface dataset:
Economic evaluation of adherence to treatment guidelines in nonintensive care pneumonia
Authors: R. Menéndez, S. Reyes, R. Martínez, P. de la Cuadra, J. Manuel Vallés, J. Vallterra
Journal: European Respiratory Journal (2006)

Guidelines have been developed to improve the treatment of community-acquired pneumonia (CAP) but information regarding their influence on costs is lacking. The aim of the present study was to conduct a cost-effectiveness analysis of CAP treatment from the hospital perspective when adhering to Spanish guidelines. A prospective cohort study was performed in 271 patients with CAP admitted to a tertiary-care hospital, not needing intensive care. Collected data included patients' characteristics, comorbidity, initial risk class, resource use (medication, blood and microbiological analyses, and radiology) and economic data. Antimicrobial treatment was recorded as adherent or nonadherent to Spanish guidelines. Outcome measures were mortality and readmission at 30 days. The median cost for adherent treatment was 1,665.5 versus 1,710.5 Euros for nonadherent treatment. Mortality and readmission were 10% and 2.1% for adherent treatment versus 13.6% and 6.2% for nonadherent treatment. The cost-effectiveness ratio was 2,277 Euros per expected cure for patients treated according to the guidelines and 2,567 Euros per expected cure for the nonadherence group. The incremental cost-effectiveness ratio showed that adherence to treatment guidelines saved 1,121 Euros per patient cured compared with nonadherence. The sensitivity analysis demonstrated that the findings were robust. An antimicrobial treatment according to guidelines is the dominant alternative due to its cost-effectiveness.
ENFORCED RESTRICTION OF COMMUNICATION, ITS IMPLICATIONS FOR THE EMOTIONAL AND INTELLECTUAL DEVELOPMENT OF THE DEAF CHILD
Authors: ROBERT L. SHAROFF
Journal: American Journal of Psychiatry (1959)

This paper does not criticize the great work that is being done to promote the meaningful growth and education of the deaf child and helping him to achieve as much oral facility as possible. It is presented in the hope that hand in hand with this, there will be a more tolerant attitude to the deaf child's need for language through signs, until such time as language through oral speech may replace it. It is felt that one may enhance the other, rather than being antithetical to each other. Some of the negative aspects of the present attitude have been presented with the hope that the questions raised here will arouse further interest in this matter and stimulate others to study this problem.
Microsatellite Instability and Loss of Heterozygosity at Chromosomal Location 18q: Prospective Evaluation of Biomarkers for Stages II and III Colon Cancer—A Study of CALGB 9581 and 89803
Authors: Monica M. Bertagnolli, Mark Redston, Carolyn C. Compton, Donna Niedzwiecki, Robert J. Mayer, Richard M. Goldberg, Thomas A. Colacchio, Leonard B. Saltz, Robert S. Warren
Journal: Journal of Clinical Oncology (2011)

Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors.We studied two of these genomic defects-mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)-in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH.Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS.We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.
Serodiagnosis of Schistosoma japonicum infection: genome-wide identification of a protein marker, and assessment of its diagnostic validity in a field study in China
Authors: Xindong Xu, Yuanbin Zhang, Dandan Lin, Jinjin Zhang, Jin Xu, Yue-min Liu, Fei Hu, Xiaoxing Qing, Chaoming Xia, Weiqing Pan
Journal: The Lancet Infectious Diseases (2014)
Hut lung: a domestically acquired pneumoconiosis of mixed aetiology in rural women.
Authors: J P Grobbelaar, E D Bateman
Journal: Thorax (1991)

A form of pneumoconiosis in rural African women termed "Transkei silicosis" has been thought to be due to silica particles inhaled while they are hand grinding maize between rocks. Twenty five women were studied who were considered to have this condition according to the following criteria: rural domicile, radiographic and lung biopsy evidence of pneumoconiosis, no exposure to mining or industry and no evidence of active tuberculosis. They were assessed for radiological, pathological, physiological and bronchoalveolar lavage fluid features. Potential aetiological factors were assessed by determining levels of exposure to respirable quartz and non-quartz containing dusts and smoke in rural dwellings during maize grinding and cooking. Most of the women were symptomless. Radiological findings ranged from a miliary pattern to extensive fibrosis resembling progressive massive fibrosis. Histological features included simple "anthracosis" in 12, anthracosis with macules in six, and mixed dust fibrosis in seven. Cell numbers and their proportions in lavage fluid were normal. More than 60% of macrophages were heavily laden with inorganic inclusions. Respirable quartz concentrations and calculated cumulative time weighted exposures were below those recommended for industry during grinding with sandstone (100% quartz) and they were even lower during grinding with dolerite containing no quartz despite the presence of an appreciable amount of quartz in the ground maize. Total respirable dust and smoke concentrations were greater than the recommended safe levels. Three women had no exposure to maize grinding. It is concluded that the inhalation of non-quartz containing dust and smoke from biomass fuelled fires is more important in the aetiology of this condition than exposure to quartz dust. The term "hut lung" may be more appropriate.
Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma
Authors: I H McKillop, C M Schmidt, P A Cahill, J V Sitzmann
Journal: Hepatology (1997)

The mitogen-activated protein kinase (MAPK) cascade acts as a focal point for signal transduction following activation of both G-protein-linked and tyrosine kinase growth factor receptors. A common intermediate between both of these diverse receptor subtypes includes the small guanosine triphosphate (GTP)-binding protein, p21 ras . Point mutations of p21 ras have been identified in various tumor types and lead to constitutive activation of this protein and subsequent activation of downstream pathways including the MAPK cascade. Using an in vivo model of hepatocellular carcinoma (HCC), we investigated the abundance and function of individual components of the MAPK cascade and the presence of specific p21 ras mutations in this model. Expression of components of the MAPK cascade were determined in tumor and adjacent, non-neoplastic liver specimens by Western blot analysis and functional activity confirmed by substrate phosphorylation assays. Mutations in p21 ras were analyzed using an enzyme-linked immunosorbent assay. In tumor, extracellular regulated kinases (ERKs) ERK1, ERK2, and mitogen-activated ERK-regulated kinase-1 (MEK1) were elevated by three-to fourfold as compared with adjacent nontumorigenic normal liver. In contrast, MEK2 was elevated by only 28%. Substrate phosphorylation and detection of phosphorylated ERK1/2 proteins showed increased functional activity of these proteins of the same magnitude as that observed for protein expression. Mutations in p21 ras were not detected in this experimental model of HCC. We conclude that HCC is associated with marked changes in expression and function of components of the MAPK cascade independent of common p21 ras mutations.
The tight junction protein ZO-2 mediates proliferation of vascular smooth muscle cells via regulation of Stat1
Authors: Angelika Kusch, Sergey Tkachuk, Natalia Tkachuk, Margret Patecki, Joon-Keun Park, Rainer Dietz, Hermann Haller, Inna Dumler
Journal: Cardiovascular Research (2009)

AimsRecent evidence suggests that the zonula occludens protein 2 (ZO-2) might have additional cellular functions, beyond regulation of paracellular permeability of epithelial and endothelial cells. Deregulation of ZO-2 in response to ischaemia, hypertensive stress, and vascular injury implies its involvement in cardiovascular disorders, most likely via regulating the functional behaviour of vascular smooth muscle cells (VSMC). However, a role of ZO-2 in VSMC biology has yet to be established. Our study was designed to understand the specific functions of ZO-2 in human VSMC.
Molecular Pathways: The PERKs and Pitfalls of Targeting the Unfolded Protein Response in Cancer
Authors: Nancy L. Maas, J. Alan Diehl
Journal: Clinical Cancer Research (2014)

Abstract The endoplasmic reticulum (ER) is a highly specialized organelle that provides an oxidizing, profolding environment for protein synthesis and maturation. The ER also hosts a dynamic signaling network that can sense and respond to physiologic changes that affect its environment, thereby influencing overall cell fate. Limitation of nutrients and oxygen have a direct effect on the efficiency of protein folding in the ER, and are classic inducers of the ER resident signaling pathway, the unfolded protein response (UPR). Not only does the UPR regulate ER homeostasis in normal cells experiencing such stress, but strong evidence also suggests that tumor cells can co-opt the cytoprotective aspects of this response to survive the hypoxic, nutrient-restricted conditions of the tumor microenvironment. Clin Cancer Res; 21(4); 675–9. ©2014 AACR.
Retinoid-induced differentiation of acute promyelocytic leukemia involves PML-RARalpha-mediated increase of type II transglutaminase
Authors: L Benedetti, F Grignani, BM Scicchitano, AM Jetten, D Diverio, F Lo Coco, G Avvisati, C Gambacorti-Passerini, S Adamo, AA Levin, PG Pelicci, C Nervi
Journal: Blood (1996)
DIRECT COMPARISON OF CMR DOBUTAMINE STRESS WALL MOTION AND PERFUSION ANALYSIS WITH ADENOSINE PERFUSION IN PATIENTS AFTER BYPASS SURGERY
Authors: Christoph Klein, Rolf Gebker, Sebastian Kelle, Bernhard Schnackenburg, Kristof Graf, Stefan Dreysse, Eckart Fleck
Journal: Journal of the American College of Cardiology (2011)
Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)
Authors: Fritz Schröder, Chris Bangma, Javier C. Angulo, Antonio Alcaraz, Marc Colombel, Tom McNicholas, Teuvo L. Tammela, Indrani Nandy, Ramiro Castro
Journal: European Urology (2012)
Pilot Studies of Wearable Outpatient Artificial Pancreas in Type 1 Diabetes
Authors: Claudio Cobelli, Eric Renard, Boris P. Kovatchev, Patrick Keith-Hynes, Najib Ben Brahim, Jérôme Place, Simone Del Favero, Marc Breton, Anne Farret, Daniela Bruttomesso, Eyal Dassau, Howard Zisser, Francis J. Doyle, Stephen D. Patek, Angelo Avogaro
Journal: Diabetes Care (2012)

The artificial pancreas (AP) has been tested extensively in the hospital setting (1–5). Here we describe a next logical step in AP development—the first outpatient trials of a wearable AP based on a smartphone computational platform.

Following Ethical Committee approvals and ClinicalTrials.gov registration (NCT01447992 and NCT01447979), two simultaneous studies were conducted in Padova, Italy, and Montpellier, France, in October 2011, enrolling a 38-year-old female and a 52-year-old male, respectively; both were Caucasian, type 1 diabetic insulin pump users.

Day 1—At 17:00, the patients arrived at hotels located within 1 km from the emergency room. Subjects’ pumps were replaced by Omnipod Insulin Management Systems. The APs were activated in open-loop mode implementing the patients’ regular routines and remote monitoring was initiated. At 20:00, the patients had dinner at a local restaurant, without dietary restrictions and then spent the night in the hotel.

Day 2—At 7:00, the patients were admitted to the clinic and the APs were switched to automated closed-loop control and challenged by breakfast at 8:00 and lunch at 12:00. At 18:00, the patients moved back to the hotel; dinner was at 20:00 in a local restaurant, without dietary restrictions. Meal bolus was recommended by the APs and approved by the patients; …
Inter-observer variation between pathologists in diffuse parenchymal lung disease
Authors: A G Nicholson
Journal: Thorax (2004)

There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study.A method for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed.The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia.These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.
THE PROTECTION OF INTRACELLULAR BRUCELLA AGAINST THERAPEUTIC AGENTS AND THE BACTERICIDAL ACTION OF SERUM
Authors: James M. Shaffer, Carrell J. Kucera, Wesley W. Spink
Journal: The Journal of Experimental Medicine (1953)

A method for the in vitro study of intracellular brucella has been described. Exudative leukocytes containing intracellular brucella have been maintained in vitro in a synthetic tissue culture medium or in human or animal serum. Intracellular brucella are protected in vitro against the lethal action of therapeutic agents or the bactericidal action of serum. This protection of intracellular brucella is dependent upon the presence of an intact, viable host cell. None of the currently available therapeutic agents, whether used alone or in combinations, were capable of killing all intracellular brucella in vitro in 24 hours. A remarkable protection of intracellular brucella against streptomycin has been demonstrated. The most effective reduction in the number of viable intracellular brucella was accomplished by exposure of the host cells to streptomycin plus aureomycin, terramycin, or chloramphenicol. The available evidence suggests that the ability of brucella to localize and remain viable within the cells of an infected host is an important biologic factor in establishing and perpetuating brucella infections, despite therapeutic measures or the operation of the host's humoral defense mechanisms. Reduction of neotetrazolium by leukocytes and brucella in vitro provides a method for assessing the metabolic status of the host cell, but does not discriminate with any degree of certainty a viable from a non-viable intracellular organism.
Novel RUNX1 mutations in familial platelet disorder with enhanced risk for acute myeloid leukemia: clues for improved identification of the FPD/AML syndrome
Authors: M C J Jongmans, R P Kuiper, C L Carmichael, E J Wilkins, N Dors, A Carmagnac, A Y N Schouten-van Meeteren, X Li, M Stankovic, E Kamping, H Bengtsson, E F P M Schoenmakers, A Geurts van Kessel, P M Hoogerbrugge, C N Hahn, P P Brons, H S Scott, N Hoogerbrugge
Journal: Leukemia (2009)
Hope for Decreasing Socioeconomic Disparities
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2015)

All patients would benefit from having a patient-centered medical home.However, Markovitz and colleagues 1 show that low-income patients may benefit more than others.Using data from adult primary care physician practices in Michigan, they show that the increases in cancer screening associated with patient-centered medical homes are greater for low-income persons.Their results intuitively make sense.Low-income persons have lower rates of receipt of preventive services owing to decreased access to medical care, lower literacy rates, language barriers, problems with transportation, increased life stress, and difficulty meeting copayments.When they are successful, patient-centered medical homes improve access and care coordination, which may help low-income patients in overcoming ob-
Erosive osteoarthritis of the hand: clinical experience with anakinra
Authors: L Bacconnier, C Jorgensen, S Fabre
Journal: Annals of the Rheumatic Diseases (2009)

Erosive osteoarthritis (EOA) is an important subtype of OA, characterised by an aggressive clinical course in perimenopausal women.1 Pain, swelling, redness, warmth and limited function of the digital joints are commonly found in most patients. Erosions (sharp marginal defects, central “crumbling” erosion, “gull-wing” deformity) are an essential hallmark for diagnosis. EOA eventually leads to joint deformity and ankylosis and is an important cause of disability, usually compared to the handicap caused by rheumatoid arthritis.

There are currently no guidelines on the best therapeutic approach in EOA, and treatments usually recommended for patients who do not have EOA (paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular injection of corticosteroids, chondroitin sulfate) …
Digital subtraction angiographic imaging of coronary flow reserve.
Authors: J T Cusma, E J Toggart, J D Folts, W W Peppler, N J Hangiandreou, C S Lee, C A Mistretta
Journal: Circulation (1987)

Recent studies have demonstrated that subjective assessment of the severity of coronary artery stenoses results in poor interobserver concordance and poor correlation with physiologic significance as determined by Doppler measurements of coronary flow reserve. Use of the coronary flow reserve as an integrated measure of the effect of stenosis geometry has been emphasized within the context of quantitative cinemetric analysis. The comparison of two parametric digital subtraction angiographic flow images obtained before and after hyperemic intervention has led to calculation of flow reserve values that correlate well with electromagnetic flowmeter data in dogs. By means of a similar model relating blood flow and image variables, single flow ratio images have been formed. These parametric images provide a two-dimensional display of the ratio of hyperemic flow to baseline flow. Linear temporal interpolation of data from a sequence of cardiac phase-matched subtraction images is used to improve the resolution of the displayed flow ratios. Summation of flow variables measured within the perfusion bed was used to calculate a value for the overall coronary flow reserve and to characterize the significance of isolated lesions in an open-chest canine preparation. A linear regression calculation relating parametric image flow ratio values to electromagnetic flowmeter measurements resulted in a linear fit of y = .96x - 0.19 with a correlation coefficient of .90. The direct visual representation of flow ratio distribution provided by the parametric imaging method may aid in the interpretation of multiple complex lesions as well as of single lesions.
Accelerated Tumor Formation in a Fatless Mouse with Type 2 Diabetes and Inflammation
Authors: Nomeli P. Nunez, Won-Jun Oh, Julian Rozenberg, Chris Perella, Miriam Anver, J. Carl Barrett, Susan N. Perkins, David Berrigan, Jaideep Moitra, Lyuba Varticovski, Stephen D. Hursting, Charles Vinson
Journal: Cancer Research (2006)

Epidemiologic studies show a positive association between obesity and cancer risk. In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. We used the fatless A-ZIP/F-1 transgenic mouse to dissociate the relative role of each of these underlying factors in the development of cancer. These mice are unique in that they do not have white fat but do develop type 2 diabetes. In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. We examined circulating levels of adipokines, growth factors, and cytokines. As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. These findings suggest that adipokines are not required for the promotion of tumor development and thus contradict the epidemiologic data linking obesity to carcinogenesis. We postulate that insulin resistance and inflammation are responsible for the positive correlation with cancer observed in A-ZIP/F-1 mice.
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact
Authors: Keren Levanon, Christopher Crum, Ronny Drapkin
Journal: Journal of Clinical Oncology (2008)

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.