tbuckley/cabot-search huggingface dataset:
Western red cedar dust exposure and lung function: a dose-response relationship.
Authors: H K Noertjojo, H Dimich-Ward, S Peelen, M Dittrick, S M Kennedy, M Chan-Yeung
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The relationship between levels of cumulative red cedar dust exposure and decline in lung function was explored in an 11-yr follow-up study of 243 sawmill workers who participated in at least two occasions. We also studied 140 office workers in a similar manner as control subjects. Workers with asthma were excluded from the analysis. During the period of the study, 916 personal and 216 area samples of dust were collected from the sawmill. Cumulative wood dust exposure was calculated for each sawmill worker according to the duration and exposure in each job, based on the geometric mean of all dust measurements for that job. Average daily dust exposure was calculated by dividing the total cumulative exposure by the number of days of work. Workers were divided into low-, medium-, and high-exposure groups with mean daily level of exposure of < 0.2, 0.2 to 0.4, and > 0.4 mg/m3, respectively. Sawmill workers had significantly greater declines in FEV1 and FVC compared with office workers adjusted for age, smoking, and initial lung function. A dose-response relationship was observed between the level of exposure and the annual decline in FVC. We conclude that exposure to Western red cedar dust is associated with a greater decline in lung function which may lead to development of chronic airflow limitation.
Echocardiography, troponins and lower extremity ultrasound: the 'Three Musketeers' lead the prognosis of acute pulmonary embolism
Authors: A. Vitarelli
Journal: Thorax (2010)

The European guidelines1 and American guidelines2 highlight that, in the diagnosis and management of acute pulmonary embolism (PE), the functional consequences determined by right ventricular (RV) dysfunction and elevation of cardiac biomarkers are more relevant for risk stratification than assessment of the anatomical burden and distribution of the pulmonary artery thrombus. The mortality rate associated with massive PE may reach 30%, while that associated with so-called submassive PE (defined as the presence of RV dysfunction without systemic hypotension) is between 5% and 10% and that associated with non-massive PE is <5%.1 While there is consensus that thrombolytic therapy, catheter embolectomy or surgery are indicated in patients with right heart failure and haemodynamic instability, the appropriate treatment of patients with submassive PE remains controversial. In this subset of patients, the ‘tricks of the trade’3 should be identified and clinical-laboratory aspects evaluated to judge the level of severity. RV echocardiographic parameters, cardiac troponins and peripheral ultrasound data are described as poor prognostic factors in the currently available literature.

Each of these tests has its own advantages and limitations. A number of studies have shown that RV dysfunction and dilation is a robust prognostic factor in acute PE. Still, some questions arise. First, the different pathophysiology of acute versus chronic pulmonary hypertension has recently been outlined.4 Similarities between PE (acute occlusive pulmonary hypertension) and chronic pulmonary hypertension include the fact that pulmonary circulatory resistance increases, RV function may decline and mortality and morbidity are correlated with the extent of RV dysfunction in both cases. Nevertheless, the mechanisms of cardiopulmonary changes are very different and result in different modes of RV injury …
Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.
Authors: A S Slutsky, R D Kamm, T H Rossing, S H Loring, J Lehr, A H Shapiro, R H Ingram, J M Drazen
Journal: Journal of Clinical Investigation (1981)

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.
The surgeon as a risk factor
Authors: D. Carter
Journal: BMJ (2003)

Surgery can be a risky business. Members of the public are now attuned to that fact and appreciate that their surgeon's performance is a key determinant of success. Outcome after surgery is of course relatively easy to assess; you survive the operation or you don't, the anastomosis holds or it doesn't, the hernia recurs or it doesn't, and so on. In an era of increased scrutiny it is perhaps no surprise that surgeons feel under pressure or that they account for a third of the referrals to the newly established National Clinical Assessment Authority in England.1

What then are the determinants of surgical performance, and is a poorly performing surgeon easy to spot? Technical skill is vital, but it is by no means the only essential ingredient for success. Thorough training, compassion, sound judgment, good communication skills, honed clinical skills, and knowledge are all critically important. Surgeons do not work in isolation and success depends on effective collaboration and team working. This is not to submerge the surgeon in anonymity—surgical teams need …
Imaging of Adrenal Masses with Emphasis on Adrenocortical Tumors
Authors: Anders Sundin
Journal: Theranostics (2012)

Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings ("incidentalomas"). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [(18)F]fluoro-deoxy-glucose ((18)FDG), is able to differentiate benign from malignant adrenal tumors in many patients. (11)C-metomidate ((11)C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.
A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses
Authors: David J. Conway, David R. Cavanagh, Kazuyuki Tanabe, Cally Roper, Zsuzsanna S. Mikes, Naoko Sakihama, Kalifa A. Bojang, Ayoade M. J. Oduola, Peter G. Kremsner, David E. Arnot, Brian M. Greenwood, Jana S. McBride
Journal: Nature Medicine (2000)
An Unholy Alliance: Cooperation between BRAF and NF1 in Melanoma Development and BRAF Inhibitor Resistance
Authors: Geoffrey T. Gibney, Keiran S.M. Smalley
Journal: Cancer Discovery (2013)

Abstract Summary: In this issue of Cancer Discovery, 2 studies provide new evidence implicating loss of the tumor suppressor neurofibromin (NF1) in the biologic behavior of cutaneous melanoma. The first study from Maertens and colleagues describes a new transgenic mouse model in which mutant BRAF cooperates with NF1 loss to drive melanoma development through the abrogation of oncogene-induced senescence. The second, from Whittaker and colleagues, used a high-throughput short hairpin RNA screening approach to identify NF1 loss as a key mediator of acquired and intrinsic BRAF inhibitor resistance. Together these studies provide new insights into the signaling that underlies melanoma initiation and progression and suggests novel therapeutic strategies for patients whose melanomas are BRAF-mutant/NF1-deficient. Cancer Discov; 3(3); 260–3. ©2013 AACR. See related article by Maertens et al., p. 338 See related article by Whittaker et al., p. 350
Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors
Authors: Y. Nieto, S.-M. Tu, R. Bassett, R.B. Jones, A.M. Gulbis, N. Tannir, A. Kingham, C. Ledesma, K. Margolin, L. Holmberg, R. Champlin, L. Pagliaro
Journal: Annals of Oncology (2015)
Co-delivery of pEGFP-hTRAIL and paclitaxel to brain glioma mediated by an angiopep-conjugated liposome
Authors: Xiyang Sun, Zhiqing Pang, Hongxing Ye, Bo Qiu, Liangran Guo, Jingwei Li, Jinfeng Ren, Yong Qian, Qizhi Zhang, Jun Chen, Xinguo Jiang
Journal: Biomaterials (2011)
Vitamin B<sub>6</sub> Metabolism
Authors: Steven L. Ink, LaVell M. Henderson
Journal: Annual Review of Nutrition (1984)

INTRODUCTION  455 DIGESTION AND ABSORPTION  456 METABOLISM AND TRANSPORT  458 STORAGE..... .........     ......... ........     462 EXCRETION .     ..... ...   ...... ... ......... 462 ASSESSMENT OF NUTRITIONAL STATUS     . 462 REQUIREMENTS   463 CLINICAL ASPECTS  465
Over 10 Years Of Experience With The Use Of C1-inhibitor Concentrate In Hereditary Angioedema, In Retrospect
Authors: H. Farkas, G. Temesszentandrási, B. Visy, G. Harmat, L. Varga, G. Füst, G. Széplaki, I. Karádi, B. Fekete, L. Jakab
Journal: Journal of Allergy and Clinical Immunology (2007)
An Improved Statistical Method for Detecting Heterotachy in Nucleotide Sequences
Authors: Guy Baele, Jeroen Raes, Yves Van de Peer, Stijn Vansteelandt
Journal: Molecular Biology and Evolution (2006)

The principle of heterotachy states that the substitution rate of sites in a gene can change through time. In this article, we propose a powerful statistical test to detect sites that evolve according to the process of heterotachy. We apply this test to an alignment of 1289 eukaryotic rRNA molecules to 1) determine how widespread the phenomenon of heterotachy is in ribosomal RNA, 2) to test whether these heterotachous sites are nonrandomly distributed, that is, linked to secondary structure features of ribosomal RNA, and 3) to determine the impact of heterotachous sites on the bootstrap support of monophyletic groupings. Our study revealed that with 21 monophyletic taxa, approximately two-thirds of the sites in the considered set of sequences is heterotachous. Although the detected heterotachous sites do not appear bound to specific structural features of the small subunit rRNA, their presence is shown to have a large beneficial influence on the bootstrap support of monophyletic groups. Using extensive testing, we show that this may not be due to heterotachy itself but merely due to the increased substitution rate at the detected heterotachous sites.
[125I]Aminobenzyladenosine, a new radioligand with improved specific binding to adenosine receptors in heart.
Authors: J Linden, A Patel, S Sadek
Journal: Circulation Research (1985)

The density of adenosine receptors in membranes derived from rat hearts in 25 times lower than the density of receptors in rat brain membranes. Consequently, adenosine radioligands which are useful in brain such as l-[3H]phenylisopropyladenosine, [3H]cyclohexyladenosine, [3H]-2-chloroadenosine and l-[125I]hydroxyphenylisopropyladenosine are of limited usefulness in heart, due to a high ratio of nonspecific to specific binding. We have synthesized a new radioligand, [125I]-N6-4-aminobenzyladenosine, which binds to rat heart membranes with one-sixth the nonspecific binding of the other radioligands. [125I]-N6-4-aminobenzyladenosine bound to rat ventricle membranes with a KD equivalent to that of l-[125I]hydroxyphenylisopropyladenosine and a Bmax of 15.2 fmol/mg protein. [125I]-N6-4-aminobenzyladenosine bound with a higher affinity to brain (KD = 1.93 nM) than to heart membranes (KD = 11.6 nM). At the radioligand KD, 60% of the total [125I]-N6-4-aminobenzyladenosine bound to heart membranes was specifically bound. Iodination of aminobenzyladenosine increased its affinity for the adenosine receptor by 22-fold, possibly due to a steric or hydrophobic effect of iodine. The new ligand was found to be a full adenosine agonist based on its ability to inhibit cyclic adenosinemonophosphate accumulation in isolated embryonic chick heart cells and rat adipocytes. [125I]-N6-4-Aminobenzyladenosine bound to a single affinity site and was displaced from cardiac and brain adenosine receptors by other adenosine analogues with a potency order of l-phenylisopropyladenosine greater than 5'-N-ethylcarboxamide adenosine. These characteristics suggest that the radioligand binds to an Ri adenosine receptor.
Supplemental oxygen and nasal intermittent positive pressure ventilation
Authors: AJ Padkin, WJ Kinnear
Journal: European Respiratory Journal (1996)

When supplementary oxygen is necessary with nasal intermittent positive pressure ventilation (NIPPV), the optimal route by which it should be added to the ventilator circuit is unknown. We investigated the oxygen concentration received when oxygen was supplied at flow rates between 0 and 6 L.min-1 into the proximal ventilator tubing or the nasal mask whilst patients were ventilated with air. Eleven patients with stable chronic hypercapnic respiratory failure were studied. A calibration curve was produced for each by supplying different known oxygen concentrations through a Monnal D or DCC ventilator and measuring the arterial oxygen saturations achieved. Oxygen was then supplied into the ventilator tubing or nasal mask and arterial saturation again measured. The oxygen concentration received was estimated using the calibration curve. Tracheal oxygen concentration throughout the respiratory cycle was studied in one patient when oxygen was supplied by both routes. Peak inspired oxygen concentration occurred at end-inspiration when oxygen was supplied into the ventilator tubing, but at mid-inspiration when supplied into the nasal mask. However, there was no significant difference between the two routes in the inspired oxygen concentration achieved at all flow rates: 1 L.min-1 supplied approximately 31% oxygen; 2 L.min-1 37%; 3 L.min-1 40%; and 4 L.min-1 44%. Flow rates above 4 L.min-1 had little additional effect. In conclusion, oxygen supplementation during nasal intermittent positive pressure ventilation can be provided into the ventilator tubing or the nasal mask with equal efficiency.
HbA1c and Coronary Heart Disease Risk Among Diabetic Patients
Authors: Wenhui Zhao, Peter T. Katzmarzyk, Ronald Horswell, Yujie Wang, Jolene Johnson, Gang Hu
Journal: Diabetes Care (2013)

Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering with coronary heart disease (CHD) risk among diabetic patients.We prospectively investigated the association of HbA1c at baseline and during follow-up with CHD risk among 17,510 African American and 12,592 white patients with type 2 diabetes.During a mean follow-up of 6.0 years, 7,258 incident CHD cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of HbA1c at baseline (<6.0 [reference group], 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, 10.0-10.9, and ≥11.0%) were 1.00, 1.07 (95% CI 0.97-1.18), 1.16 (1.04-1.31), 1.15 (1.01-1.32), 1.26 (1.09-1.45), 1.27 (1.09-1.48), and 1.24 (1.10-1.40) (P trend = 0.002) for African Americans and 1.00, 1.04 (0.94-1.14), 1.15 (1.03-1.28), 1.29 (1.13-1.46), 1.41 (1.22-1.62), 1.34 (1.14-1.57), and 1.44 (1.26-1.65) (P trend <0.001) for white patients, respectively. The graded association of HbA1c during follow-up with CHD risk was observed among both African American and white diabetic patients (all P trend <0.001). Each one percentage increase of HbA1c was associated with a greater increase in CHD risk in white versus African American diabetic patients. When stratified by sex, age, smoking status, use of glucose-lowering agents, and income, this graded association of HbA1c with CHD was still present.The current study in a low-income population suggests a graded positive association between HbA1c at baseline and during follow-up with the risk of CHD among both African American and white diabetic patients with low socioeconomic status.
Beyond the Cancer Cell: Progression-Level Determinants Highlight the Multiscale Nature of Carcinogenesis Risk
Authors: Lynn Hlatky, Philip Hahnfeldt
Journal: Cancer Research (2013)

Abstract Over the last several decades, improved awareness of the prevalence of carcinogens in the environment, along with a growing appreciation of the complexity of the carcinogenesis process, has shifted policy on cancer risk from one of strict avoidance of carcinogens to one of adherence to exposure limits deemed “safe” based on quantitative risk estimation. Meanwhile, given the mutagenic nature of most carcinogens, attention has gravitated to developing a genetic rationale for measuring and comparing risks. This focus has culminated in the now well-established multistage mutational paradigm, which holds that a stepwise sequence of mutations drives cell “initiation” and the subsequent “transformation” of an initiated cell into a cancer cell, and that, once created, a cancer cell will inevitably undergo “progression” to become overt disease. Unanticipated by this paradigm is the effect progression-phase population- and tissue-level bottleneck events may have on this process. Attesting to this is the prevalence of tumor dormancy, a state of arrested growth of an otherwise fully malignant, often microscopic cancer mass, maintained by interactions among cancer cells and between cancer and host cells. The proper inclusion of such progression-modifying influences would clearly behoove risk estimation and improve our understanding of the natural history of cancer by accounting for the less-than-certain risk of eventual cancer disease even when cancer cells are present. Such an improved understanding, in turn, stands to better inform policy-making and influence such clinical practice decisions as whether to treat the increasingly smaller tumors detectable with advancing technologies. Cancer Res; 74(3); 659–64. ©2013 AACR.
Synergistic Targeting of AML Stem/Progenitor Cells With IAP Antagonist Birinapant and Demethylating Agents
Authors: Bing Z. Carter, Po Yee Mak, Duncan H. Mak, Yuexi Shi, Yihua Qiu, James M. Bogenberger, Hong Mu, Raoul Tibes, Hui Yao, Kevin R. Coombes, Rodrigo O. Jacamo, Teresa McQueen, Steven M. Kornblau, Michael Andreeff
Journal: JNCI Journal of the National Cancer Institute (2014)

Acute myeloid leukemia (AML) therapy has limited long-term efficacy because patients frequently develop disease relapse because of the inability of standard chemotherapeutic agents to target AML stem/progenitor cells. Here, we identify deregulated apoptotic components in AML stem/progenitor cells and investigate the individual and combinatorial effects of the novel inhibitor of apoptosis (IAP) protein antagonist and second mitochondrial-derived activator of caspases (SMAC) mimetic birinapant and demethylating epigenetic modulators. Protein expression was measured by reversed-phase protein array in AML patient (n = 511) and normal (n = 21) samples and by western blot in drug-treated cells. The antileukemic activity of birinapant and demethylating agents was assessed in vitro and in an in vivo AML mouse xenograft model (n = 10 mice per group). All statistical tests were two-sided. Compared with bulk AML cells, CD34 + 38 − AML stem/progenitors expressed increased cIAP1 and caspase-8 levels and decreased SMAC levels (one-way analysis of variance followed by Tukey's multiple comparison test, P < .001). Birinapant induced death receptor–/caspase-8–mediated apoptosis in AML cells, including in AML stem/progenitor cells, but not in normal CD34 + cells. Demethylating agents modulated extrinsic apoptosis pathway components and, when combined with birinapant, were highly synergistic in vitro (combination index < 1), and also more effective in vivo ( P < .001, by Student t test, for the median survival of birinapant plus 5-azacytadine vs birinapant alone or vs controls). cIAP1, SMAC, and caspase-8 appear to play a role in AML stem cell survival, and synergistic targeting of these cells with birinapant and demethylating agents shows potential utility in leukemia therapy.
A Single Session With an Earthquake Simulator for Traumatic Stress in Earthquake Survivors
Authors: Metin Başoğlu, Maria Livanou, Ebru Salcioğlu
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study examined the effectiveness of a single session of earthquake simulator-assisted exposure treatment of traumatic stress in earthquake survivors. METHOD: Ten earthquake survivors in Turkey were given one session of exposure to simulated earthquake tremors. Assessments were at pre- and postsession and at 2, 4, 8, and 12 weeks posttreatment. RESULTS: All measures showed significant improvement at all assessments. Eight patients were markedly and two slightly improved at follow-up. CONCLUSIONS: A single exposure session with an earthquake simulator appears to be effective in treating postearthquake traumatic stress. Controlled studies are needed to confirm these findings.
Absorption of nicotine and carbon monoxide from passive smoking under natural conditions of exposure.
Authors: M J Jarvis, M A Russell, C Feyerabend
Journal: Thorax (1983)

Seven non-smokers were exposed to tobacco smoke under natural conditions for two hours in a public house. Measures of nicotine and cotinine in plasma, saliva, and urine and expired air carbon monoxide all showed reliable increases. The concentrations of carbon monoxide and nicotine after exposure averaged 15.7% and 7.5% respectively of the values found in heavy smokers. Although the increase in expired air carbon monoxide of 5.9 ppm was similar to increases in smokers after a single cigarette, the amount of nicotine absorbed was between a tenth and a third of the amount taken in from one cigarette. Since this represented a relatively extreme acute natural exposure, any health risks of passive smoking probably depend less on quantitative factors than on qualitative differences between sidestream and mainstream smoke.
Caveolae and Caveolins in the Cardiovascular System
Authors: Jean-Philippe Gratton, Pascal Bernatchez, William C. Sessa
Journal: Circulation Research (2004)

Caveolae and the caveolae coat proteins, caveolins, are putatively implicated in many cellular processes, including transcytosis of macromolecules, cholesterol transport, and signal transduction. Recent insights into the physiological and pathophysiological roles of these organelles and the caveolins from genetically modified mice suggest that they may be profoundly important for postnatal cardiovascular function, including endothelial barrier function, regulation of nitric oxide synthesis, cholesterol metabolism, and cardiac function.