tbuckley/cabot-search huggingface dataset:
A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis
Authors: Rudolf K.F. Oliveira, Carlos A.C. Pereira, Roberta P. Ramos, Eloara V.M. Ferreira, Carolina M.S. Messina, Lilian T. Kuranishi, Andrea Gimenez, Orlando Campos, Célia M.C. Silva, Jaquelina S. Ota-Arakaki
Journal: European Respiratory Journal (2014)

Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean± sd 50±17% versus 69±22% predicted, p&lt;0.01), carbon monoxide diffusing capacity (37±12% versus 47±14% predicted, p&lt;0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8–69.3) versus 73.0 (62.2–78.5) mmHg, p&lt;0.01) and saturation after the 6-min walk test (78±8% versus 86±7%, p&lt;0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41±11% versus 50±8% predicted, p=0.04) and at peak exercise (12.8±1.6 versus 15.0±2.5 mL·kg −1 ·min −1 , p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity.
Distinct Roles for Mammalian Target of Rapamycin Complexes in the Fibroblast Response to Transforming Growth Factor-β
Authors: Rod A. Rahimi, Mahefatiana Andrianifahanana, Mark C. Wilkes, Maryanne Edens, Theodore J. Kottom, John Blenis, Edward B. Leof
Journal: Cancer Research (2008)

Abstract Transforming growth factor-β (TGF-β) promotes a multitude of diverse biological processes, including growth arrest of epithelial cells and proliferation of fibroblasts. Although the TGF-β signaling pathways that promote inhibition of epithelial cell growth are well characterized, less is known about the mechanisms mediating the positive response to this growth factor. Given that TGF-β has been shown to promote fibrotic diseases and desmoplasia, identifying the fibroblast-specific TGF-β signaling pathways is critical. Here, we investigate the role of mammalian target of rapamycin (mTOR), a known effector of phosphatidylinositol 3-kinase (PI3K) and promoter of cell growth, in the fibroblast response to TGF-β. We show that TGF-β activates mTOR complex 1 (mTORC1) in fibroblasts but not epithelial cells via a PI3K-Akt-TSC2–dependent pathway. Rapamycin, the pharmacologic inhibitor of mTOR, prevents TGF-β–mediated anchorage-independent growth without affecting TGF-β transcriptional responses or extracellular matrix protein induction. In addition to mTORC1, we also examined the role of mTORC2 in TGF-β action. mTORC2 promotes TGF-β–induced morphologic transformation and is required for TGF-β–induced Akt S473 phosphorylation but not mTORC1 activation. Interestingly, both mTOR complexes are necessary for TGF-β–mediated growth in soft agar. These results define distinct and overlapping roles for mTORC1 and mTORC2 in the fibroblast response to TGF-β and suggest that inhibitors of mTOR signaling may be useful in treating fibrotic processes, such as desmoplasia. [Cancer Res 2009;69(1):84–93]
Scleromyxedema (lichen myxedematosus) associated with dermatomyositis
Authors: D. Launay, P-Y. Hatron, E. Delaporte, E. Hachulla, B. Devulder, F. Piette
Journal: British Journal of Dermatology (2001)

Journal Article Scleromyxedema (lichen myxedematosus) associated with dermatomyositis Get access D. Launay, D. Launay Departments of Internal Medicine and Dr David Launay. E‐mail: dlaunay@caramail.com Search for other works by this author on: Oxford Academic Google Scholar P‐Y. Hatron, P‐Y. Hatron Departments of Internal Medicine and Search for other works by this author on: Oxford Academic Google Scholar E. Delaporte, E. Delaporte Dermatology, Claude Huriez Hospital; 1, place de Verdun, 59037 Lille Cedex. France Search for other works by this author on: Oxford Academic Google Scholar E. Hachulla, E. Hachulla Departments of Internal Medicine and Search for other works by this author on: Oxford Academic Google Scholar B. Devulder, B. Devulder Departments of Internal Medicine and Search for other works by this author on: Oxford Academic Google Scholar F. Piette F. Piette Dermatology, Claude Huriez Hospital; 1, place de Verdun, 59037 Lille Cedex. France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 2, 1 February 2001, Pages 359–362, https://doi.org/10.1046/j.1365-2133.2001.04027.x Published: 01 February 2001
Central Catheter–Associated Bloodstream Infection Reduction With Ethanol Lock Prophylaxis in Pediatric Intestinal Failure
Authors: Monica I. Ardura, Jeffrey Lewis, Jessica L. Tansmore, Patricia L. Harp, Molly C. Dienhart, Jane P. Balint
Journal: JAMA Pediatrics (2015)

Children with intestinal failure are at high risk for developing central catheter-associated bloodstream infections (CCABSIs) owing to children's chronic dependence on central venous catheters for parenteral nutrition.To evaluate the effectiveness and safety of the addition of ethanol lock prophylaxis to a best-practice CCABSI prevention bundle on hospital and ambulatory CCABSI rates in children with intestinal failure.Quality improvement and statistical process control analysis that took place at a tertiary care pediatric hospital and patient homes. Participants included children who were 18 years or younger with intestinal failure requiring a central venous catheter.Central catheter-associated bloodstream infection prevention bundle that included daily ethanol lock prophylaxis.Central catheter-associated bloodstream infection rates and safety outcomes (central catheter insertions, repairs, and hospitalizations) before (January 1, 2011-January 31, 2012) and after (February 1, 2012-December 31, 2013) ethanol lock prophylaxis bundle implementation.Twenty-four children with intestinal failure received the ethanol lock prophylaxis CCABSI prevention bundle for a median of 266 days (range, 12-635 days). Rates of CCABSI decreased from 6.99 CCABSIs per 1000 catheter days at baseline to 0.42 CCABSI per 1000 catheter days after ethanol lock prophylaxis bundle implementation, despite an increase in the total number of catheter days. A subset of 14 children who received prolonged ethanol lock prophylaxis (≥3 months) had fewer median (range) central catheter insertions 0 (0-2) vs 3 (0-6); P = .001. The pre-ELP intervention CCABSI rates in this subset was 7.01 per 1000 catheter days vs 0.64 per 1000 catheter days for post-ELP intervention (P = .004). There were no significant differences in the total number of hospital admissions; however, there were fewer hospitalizations for fever and CCABSI (P = .003).A best-practice CCABSI prevention bundle that included ethanol lock prophylaxis in both the hospital and home was successfully implemented, well tolerated, and demonstrated a significant and sustained reduction in preventable harm in the form of CCABSIs in children with intestinal failure.
The Theory and Practice of Psychiatry
Authors: Samuel Friedman
Journal: JAMA (1966)

No run-of-the-mill psychiatric textbook is this. Monumental in a number of respects, its sheer size is impressive—almost 900 pages of compactly printed text and not far from half a million words.  Not surprisingly, in view of the senior author's interests, psychoanalytical and psychosocial emphasis is the keynote, yet no phase of psychiatric investigation has been neglected. The historical survey is excellent. It is refreshing to see an effective section on pharmacological treatment. But the core of the book, which ranks with the best in psychiatric thought, is the discussions of normal and abnormal behavior, neurotic reactions, psychosomatic diseases, and schizophrenias. The authors search not merely for the what but for the why and how. Interpretation, the attempt to get at the raison d'etre, is paramount.  The attitude toward the causes of schizophrenia is highly ambivalent. At one point the authors incline to concepts of constitutional defect, possibly genetic, conceivably a
Expression of <i>NLRR3</i> Orphan Receptor Gene Is Negatively Regulated by MYCN and Miz-1, and Its Downregulation Is Associated with Unfavorable Outcome in Neuroblastoma
Authors: Jesmin Akter, Atsushi Takatori, Md. Shamim Hossain, Toshinori Ozaki, Atsuko Nakazawa, Miki Ohira, Yusuke Suenaga, Akira Nakagawara
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Our previous study showed that expression of NLRR3 is significantly high in favorable neuroblastomas (NBL), whereas that of NLRR1 is significantly high in unfavorable NBLs. However, the molecular mechanism of transcriptional regulation of NLRR3 remains elusive. This study was undertaken to clarify the transcriptional regulation of NLRR3 and its association with the prognosis of NBL. Experimental Design: NLRR3 and MYCN expressions in NBL cell lines were analyzed after induction of cell differentiation, MYCN knockdown, and overexpression. The transcriptional regulation of NLRR3 was analyzed by luciferase reporter and chromatin immunoprecipitation assays. Quantitative PCR was used for examining the expression of NLRR3, Miz-1, or MYCN in 87 primary NBLs. Results: The expression of NLRR3 mRNA was upregulated during differentiation of NBL cells induced by retinoic acid, accompanied with reduced expression of MYCN, suggesting that NLRR3 expression was inversely correlated with MYCN in differentiation. Indeed, knockdown of MYCN induced NLRR3 expression, whereas exogenously expressed MYCN reduced cellular NLRR3 expression. We found that Miz-1 was highly expressed in favorable NBLs and NLRR3 was induced by Miz-1 expression in NBL cells. MYCN and Miz-1 complexes bound to NLRR3 promoter and showed a negative regulation of NLRR3 expression. In addition, a combination of low expression of NLRR3 and high expression of MYCN was highly associated with poor prognosis. Conclusions: NLRR3 is a direct target of MYCN, which associates with Miz-1 and negatively regulates NLRR3 expression. NLRR3 may play a role in NBL differentiation and the survival of NBL patients by inversely correlating with MYCN amplification. Clin Cancer Res; 17(21); 6681–92. ©2011 AACR.
Early versus Later Rhythm Analysis in Patients with Out-of-Hospital Cardiac Arrest
Authors: Ian G. Stiell, Graham Nichol, Brian G. Leroux, Thomas D. Rea, Joseph P. Ornato, Judy Powell, James Christenson, Clifton W. Callaway, Peter J. Kudenchuk, Tom P. Aufderheide, Ahamed H. Idris, Mohamud R. Daya, Henry E. Wang, Laurie J. Morrison, Daniel Davis, Douglas Andrusiek, Shannon Stephens, Sheldon Cheskes, Robert H. Schmicker, Ray Fowler, Christian Vaillancourt, David Hostler, Dana Zive, Ronald G. Pirrallo, Gary M. Vilke, George Sopko, Myron Weisfeldt
Journal: New England Journal of Medicine (2011)

In a departure from the previous strategy of immediate defibrillation, the 2005 resuscitation guidelines from the American Heart Association–International Liaison Committee on Resuscitation suggested that emergency medical service (EMS) personnel could provide 2 minutes of cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm. We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm.
DISTRIBUTION OF PUBIC HAIR IN A SAMPLE OF FIT MEN.
Authors: DONALD McGREGOR
Journal: British Journal of Dermatology (1961)

Journal Article DISTRIBUTION OF PUBIC HAIR IN A SAMPLE OF FIT MEN. Get access DONALD McGREGOR, M.A., M.R.C.S., L.R.C.P. DONALD McGREGOR, M.A., M.R.C.S., L.R.C.P. General Practitioner, Bonar Bridge, Sutherland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 2, 1 February 1961, Pages 61–64, https://doi.org/10.1111/j.1365-2133.1961.tb14408.x Published: 01 February 1961
Statins, Fibrates, and Melanoma Risk: a Systematic Review and Meta-analysis
Authors: Scott R. Freeman, Amanda L. Drake, Lauren F. Heilig, Marla Graber, Kristie McNealy, Lisa M. Schilling, Robert P. Dellavalle
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Large randomized, controlled clinical trials of lovastatin and gemfibrozil for heart disease prevention have reported statistically significantly lower melanoma incidences in persons receiving these medications. Results of in vitro animal model and human case–control studies also suggest that statins and fibrates may reduce the risk of melanoma. Methods: We performed a systematic review of trials that randomly assigned participants to receive statins or fibrates versus an alternative therapy for a minimum of 6 months. Trials were identified by searching five electronic databases and the reference lists of eligible publications. Unpublished data were solicited from trial investigators and pharmaceutical companies. A meta-analysis was performed using a fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate pooled treatment effects. All statistical tests were two-sided. Results: We obtained data on incident melanomas from 20 of 36 qualifying randomized controlled trials (12 statin trials and eight fibrate trials), with a total of 70 820 participants. A total of 127 melanomas occurred among the 39 426 participants in the statin trials (59 among the 19 872 statin group participants and 68 among the 19 554 control group participants). A total of 27 melanomas occurred among the 31 394 participants enrolled in the fibrate trials (seven among the 12 324 fibrate group participants and 20 among the 19 070 control group participants). Overall, incidence of melanoma was not statistically significantly associated with the use of either statins (OR = 0.87, 95% CI = 0.61 to 1.23) or fibrates (OR = 0.45, 95% CI = 0.20 to 1.01). In a subgroup analysis by drug, only lovastatin use (in one trial) was statistically significantly associated with lower incidence of melanoma (OR = 0.52, 95% CI = 0.27 to 0.99). Conclusions: These findings do not validate the possibility that statins or fibrates prevent melanoma.
The prevalence of pili multigemini
Authors: L. Lester, C. Venditti
Journal: British Journal of Dermatology (2007)

Journal Article The prevalence of pili multigemini Get access L. Lester, L. Lester School of Biological Sciences, The University of Reading, Whiteknights, PO Box 228, Reading RG6 6AJ, U.K. E‐mail: r.l.lester@reading.ac.uk Search for other works by this author on: Oxford Academic Google Scholar C. Venditti C. Venditti School of Biological Sciences, The University of Reading, Whiteknights, PO Box 228, Reading RG6 6AJ, U.K. E‐mail: r.l.lester@reading.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 6, 1 June 2007, Page 1362, https://doi.org/10.1111/j.1365-2133.2007.07868.x Published: 01 June 2007
Pathogenesis of Mitral Regurgitation in Tachycardia-Induced Cardiomyopathy
Authors: Tomasz A. Timek, Paul Dagum, David T. Lai, David Liang, George T. Daughters, Neil B. Ingels, D. Craig Miller
Journal: Circulation (2001)

Dilated cardiomyopathy is often associated with mitral regurgitation (MR), or so-called functional MR, the mechanism of which continues to be debated. We studied the valvular and ventricular 3D geometric perturbations associated with MR in an ovine model of tachycardia-induced cardiomyopathy (TIC).Nine sheep underwent myocardial marker implantation in the left ventricle (LV), mitral annulus, and mitral leaflets. After 5 to 8 days, the animals were studied with biplane videofluoroscopy (baseline), and mitral competence was assessed by transesophageal echocardiography. Rapid ventricular pacing (180 to 230 bpm) was subsequently initiated for 15+/-6 days until the development of TIC and MR, whereupon biplane videofluoroscopy and transesophageal echocardiography studies were repeated. LV volume was calculated from the epicardial marker array. Valve closure time was defined as the time after end diastole when the distance between leaflet edge markers reached its minimal plateau. TIC resulted in increased LV end-diastolic volume (P=0.001) and LV end-systolic volume (P=0.0001) and greater LV sphericity (P=0.02). MR increased significantly (grade 0.2+/-0.3 versus 2.2+/-0.9, P=0.0001), as did mitral annulus area (817+/-146 versus 1100+/-161 mm(2), P=0.0001) and mitral annulus septal-lateral diameter (28.2+/-3.5 versus 35.1+/-2.6 mm, P=0.0001). Time of valve closure (70+/-18 versus 87+/-14 ms, P=0.23) and angular displacement of both the anterior (29+/-5 degrees versus 27+/-3 degrees, P=0.3) and posterior (55+/-15 degrees versus 44+/-11 degrees, P=0.13) leaflet edges relative to the mitral annulus after valve closure did not change, but leaflet edge separation after closure increased (5.2+/-0.9 versus 6.8+/-1.2 mm, P=0.019).MR in TIC resulted from decreased leaflet coaptation secondary to annular dilatation in the septal-lateral direction. These data support the use of annular reduction procedures, such as rigid, complete ring annuloplasty, to address functional MR in patients with dilated cardiomyopathy.
P<scp>ROTOFIBRILS</scp>, P<scp>ORES</scp>, F<scp>IBRILS, AND</scp> N<scp>EURODEGENERATION</scp>: Separating the Responsible Protein Aggregates from The Innocent Bystanders
Authors: Byron Caughey, Peter T. Lansbury
Journal: Annual Review of Neuroscience (2003)

▪ Abstract Many neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates.
Phase III Comparison of Tamoxifen Versus Tamoxifen Plus Ovarian Function Suppression in Premenopausal Women With Node-Negative, Hormone Receptor–Positive Breast Cancer (E-3193, INT-0142): A Trial of the Eastern Cooperative Oncology Group
Authors: Amye J. Tevaarwerk, Molin Wang, Fengmin Zhao, John H. Fetting, David Cella, Lynne I. Wagner, Silvana Martino, James N. Ingle, Joseph A. Sparano, Lawrence J. Solin, William C. Wood, Nicholas J. Robert
Journal: Journal of Clinical Oncology (2014)

Purpose The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods Premenopausal women with axillary node-negative, hormone receptor–positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P &lt; .01 for all). Differences diminished with further follow-up. Conclusion When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.
Nasal airflow resistance at simulated altitude
Authors: J.G. Widdicombe
Journal: European Respiratory Journal (2001)

This issue includes an important paper by BARRY et al. [1] in which the changes in nasal peak inspiratory flow (NPIF), and oral peak inspiratory flow (OPIF), during acclimatized exposure to low barometric pressure (equivalent to a simulated altitude of 8000 m, about the height of Mount Everest) of subjects in a hypobaric chamber were analysed.The changes were presumably due to hypoxia and its chemical sequelae, and influenced by the processes of acclimatization.They show that NPIF increases by a mean of 16%, whereas OPIF increases by 47%, and conclude that these results are consistent with a decrease in upper airways luminal calibre at altitude, correlating with the symptomatic nasal blockage and impairment of mucociliary function seen in similar conditions.The changes must be due to chronic hypoxia rather than to inhalation of cold and dry air, since environmental temperature and humidity were maintained at values close to those found at sea level.The study is important because it may point to physiological mechanisms determining airway calibre at altitude, and to changes in the airways that will influence breathing at altitude.The authors must have confronted formidable problems in experimental design, since their subjects were confined to a hypobaric chamber for over a month, and the apparatus which could be used to assess their airway mechanics must inevitably have been limited.The authors fully justify their use of rather simple methods to assess airways9 resistances.However, while these limitations can be appreciated, there are important considerations about the methodology and interpretation of results.A clear distinction between airways9 conductance, airways9 resistance and airways9 calibre needs to be made.The former two are reciprocally related and depend, inter alia, on the viscosity and density of the transmitted gas, and other aerodynamic features; however calibre will affect both conductance and resistance, but is not directly affected by the physical properties of the gas.NPIF and OPIF primarily reflect airways9 conductance.NPIF and OPIF are rather imprecise indications of airways9 conductance.If, as the authors found, lower airways9 inspiratory conductance (OPIF) is increased