tbuckley/cabot-search huggingface dataset:
Shape of small opacities and lung function in coalworkers.
Authors: A Cockcroft, G Berry, J E Cotes, J P Lyons
Journal: Thorax (1982)

Lung function and chest radiographs were reviewed in 357 coalworkers who had been referred from the Cardiff Pneumoconiosis Medical Panel. The chest films were read according to the 1980 ILO classification of radiographs by three experienced readers. An irregularity score, reflecting the shape of the small opacities, was derived from the readings and compared with the lung function variables. Men with higher irregularity scores had significant reductions in ventilatory capacity and gas transfer factor, with no change in total lung capacity, after age, height, profusion of small opacities, and smoking habit had been taken into account. The effects were present both in those with and in those without large opacities. The agreement between readers over the shape of opacities was almost as good as for their profusion. Men with rounded opacities had a lower gas transfer factor if they were predominantly of the "p" type. The results are consistent with those for a combination of emphysema and interstitial fibrosis, which has been found in coalworkers with irregular opacities.
Gastric acid secretion in uraemia and circulating levels of gastrin, somatostatin, and pancreatic polypeptide.
Authors: R Hallgren, J Landelius, K E Fjellstrom, G Lundqvist
Journal: Gut (1979)

Basal circulating levels of gastrin, somatostatin, and pancreatic polypeptide were measured in 30 chronic haemodialysis patients. Five patients had considerably raised serum gastrin (greater than 400 pmol/1) and also gastric achlorhydria while 75% of the patients who had normal (less than 55 pmol/1) or moderately increased (less than 400 pmol/1) serum gastrin had raised maximal acid outputs. Patients with serum gastrin greater than 400 pmol/1 had significantly lower plasma concentrations of somatostatin compared with both healthy individuals and uaremic patients with normal gastrin levels. Raised serum concentrations of pancreatic polypeptide were observed in the majority of the patients but no correlation was found between this peptide and gastric acid secretion or circulating levels of gastrin and somatostatin, respectively. Prolonged circulation time for gastrin and pancreatic polypeptide was demonstrated after food stimulation. Prolonged gastrin stimulation of the parietal cell mass may lead to work hypertrophy and gastric acid hypersecretion. Whether long-standing over-stimulation by gastrin also may induce atrophy of the cells remains to be studied.
GROWTH CONE GUIDANCE: First Steps Towards a Deeper Understanding
Authors: Bernhard K. Mueller
Journal: Annual Review of Neuroscience (1999)

▪ Abstract Growth cones, the hand-like structures at the tip of growing neurites, possess remarkable abilities to detect directional cues. On their way to their targets they traverse a dense jungle of many different cells, expressing a variety of different molecular guidance cues. Proper reading and integration of these cues is essential for precise wiring of different parts of the peripheral and central nervous systems. Guidance cues have been classified according to the response they elicit as either attractive or repulsive. Recent work, however, suggests that this might not represent an absolute distinction and that the internal state of the growth cone can dictate whether it detects a cue as repulsive or attractive. This article reviews some new experimental approaches to understanding growth cone signal transduction mechanisms induced by extracellular guidance cues.
Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance
Authors: Roel G. W. Verhaak, Chantal S. Goudswaard, Wim van Putten, Maarten A. Bijl, Mathijs A. Sanders, Wendy Hugens, André G. Uitterlinden, Claudia A. J. Erpelinck, Ruud Delwel, Bob Löwenberg, Peter J. M. Valk
Journal: Blood (2005)
WHO and the pandemic flu "conspiracies"
Authors: Deborah Cohen, Philip Carter
Journal: BMJ (2010)

Key scientists advising the World Health Organization on planning for an influenza pandemic had done paid work for pharmaceutical firms that stood to gain from the guidance they were preparing. These conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.” <b>Deborah Cohen</b> and <b>Philip Carter</b> investigate
Socially Tolerable Cigarette Smoke?
Authors: F. Homburger
Journal: JAMA (1979)

<h3>To the Editor.—</h3> <i>The Wall Street Journal</i>(Nov 1, 1978, p 18) suggests that "because of news accounts of a study by Gio B. Gori... much of the public [was left] with the impression that some cigarettes are relatively safe to smoke in limited quantity." The article reports that because of this, "Smokers of extremely low-tar cigarettes, who were once largely ignored by the industry, are the targets of intensifying market competition." This calls for a close look at the article by Gori and Lynch (240:1255, 1978), who conclude that smokers who would not exceed certain levels of intake of tar, nicotine, carbon monoxide, nitrogen oxides, hydrogen cyanide, and acrolein would subject themselves to a risk which could be considered "socially tolerable." Before 1960, smoking two cigarettes per day exposed the smoker to amounts of the aforementioned substances, which were tolerated without demonstrable epidemiologic effect. Gori and Lynch calculated the
Resident Work Hours and Working Environment in Otolaryngology
Authors: C L Strunk, B J Bailey, B A Scott, C W Cummings, F E Lucente, C W Beatty, H B Neel, H C Pillsbury, D H Rice, M D Bryan
Journal: JAMA (1991)

--To analyze the working environment and work hours of a cohort of otolaryngology--head and neck surgery residents.--Environmental analysis questionnaire and a log of daily activities.--Residents were on a clinical rotation system.--Fifty-nine residents from six programs, including three public and three private institutions, from geographically diverse regions of the country were involved in the study. Residents were equally distributed from their second year through their fifth year of postgraduate work. All eligible residents participated in and completed the study.--The environmental analysis survey was designed to elicit resident perception of different aspects of their working environment. The daily activity log required the resident to report on activities for each half-hour period for 7 consecutive days.--Residents were on call an average of 52.8 hours (2.2 days) and worked 79.4 hours per week. Seventy-five percent believed that the level of faculty supervision and the degree of resident responsibility was about right. Two major inefficiencies were the time involved in completion of paperwork and the lack of nonmedical support services. Thirty-one percent of the residents responded that fatigue resulted in substandard patient care 10% of the time. Forty-seven percent responded that their educational experience was substandard 25% of the time secondary to fatigue. Two thirds responded that the demands of residency training had a negative impact on their family and personal life.--Seventy percent of the otolaryngology--head and neck surgery residents surveyed at six institutions believe that an 80-hour workweek, including being on call every third night with no more than 24 hours of continuous work without sleep, approximates a reasonable, maximum work schedule. Residents working the longest hours expressed concern about rendering substandard care and developing negative attitudes toward patients. Noneducational inefficiencies were identified and solutions were proposed. Demands of residency training, even within guidelines established as reasonable, can have detrimental effects on residents' educational activities and personal life.
Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Authors: Peter H. Wiernik, Izidore S. Lossos, Joseph M. Tuscano, Glen Justice, Julie M. Vose, Craig E. Cole, Wendy Lam, Kyle McBride, Kenton Wride, Dennis Pietronigro, Kenichi Takeshita, Annette Ervin-Haynes, Jerome B. Zeldis, Thomas M. Habermann
Journal: Journal of Clinical Oncology (2008)

The major cause of death in aggressive lymphoma is relapse or nonresponse to initial therapy. Lenalidomide has activity in a variety of hematologic malignancies, including non-Hodgkin's lymphoma (NHL). We report the results of a phase II, single-arm, multicenter trial evaluating the safety and efficacy of lenalidomide oral monotherapy in patients with relapsed or refractory aggressive NHL.Patients were treated with oral lenalidomide 25 mg once daily on days 1 to 21, every 28 days, for 52 weeks, until disease progression or intolerance. The primary end point was response; secondary end points included duration of response, progression-free survival (PFS), and safety.Forty-nine patients with a median age of 65 years received lenalidomide in this study. The most common histology was diffuse large B-cell lymphoma (53%), and patients had received a median of four prior treatment regimens for NHL. An objective response rate of 35% was observed in 49 treated patients, including a 12% rate of complete response/unconfirmed complete response. Responses were observed in each aggressive histologic subtype tested (diffuse large B-cell, follicular center grade 3, mantle cell, and transformed lymphomas). Of patients with stable disease or partial response at first assessment, 25% improved with continued treatment. Estimated median duration of response was 6.2 months, and median PFS was 4.0 months. The most common grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%); the most common grade 3 adverse events were neutropenia (24.5%), leukopenia (14.3%), and thrombocytopenia (12.2%).Oral lenalidomide monotherapy is active in relapsed or refractory aggressive NHL, with manageable side effects.
Performance and prognosis in patients with lung cancer. The Edinburgh Lung Cancer Group.
Authors: S Capewell, M F Sudlow
Journal: Thorax (1990)

The Edinburgh Lung Cancer Group prospectively registered 651 new patients presenting with lung cancer during 1981; only 47 survived five years (7%). The survival rate was highest in patients selected for surgery (35/116, 30%) and in this group was related to cell type, stage of disease, and possibly to Karnofsky performance score (not statistically significant). By comparison with non-surgical patients these 116 patients undergoing surgery were highly selected in terms of age, favourable histological type, stage of disease, and performance score. Forty-two of the 535 non-surgical patients were given radical radiotherapy alone and seven (17%) survived five years. The remaining 493 received palliative radiotherapy, chemotherapy (alone or combined with radiotherapy), or symptomatic treatment alone; only five (1%) survived five years. Median survival was related to cell type (adenocarcinoma 2.6 months, squamous cell carcinoma 6.2 months), stage (stage I 8.5 months, stage III 4 months), and Karnofsky performance index (greater than or equal to 90 9.3 months, less than or equal to 50 1.2 months). Age and sex had no independent prognostic value in any group. Performance score was highly correlated with stage (and age) and in this study represented the "best prognostic factor" in clinical practice.
Epicardial function of canonical Wnt-, Hedgehog-, Fgfr1/2-, and Pdgfra-signalling
Authors: Carsten Rudat, Julia Norden, Makoto Mark Taketo, Andreas Kispert
Journal: Cardiovascular Research (2013)

The embryonic epicardium is a source of smooth muscle cells and fibroblasts of the coronary vasculature and of the myocardium, but the signalling pathways that control mobilization and differentiation of epicardial cells are only partly known. We aimed to (re-)evaluate the relevance of canonical Wnt-, Hedgehog (Hh)-, Fibroblast growth factor receptor (Fgfr)1/2-, and platelet-derived growth factor receptor alpha (Pdgfra)-signalling in murine epicardial development. We used a T-box 18 (Tbx18)cre-mediated conditional approach to delete and to stabilize, respectively, the downstream mediator of canonical Wnt-signalling, beta-catenin (Ctnnb1), to delete and activate the mediator of Hh-signalling, smoothened (Smo), and to delete Fgfr1/Fgfr2 and Pdgfra in murine epicardial development. We show that epicardial loss of Ctnnb1, Smo, or Fgfr1/Fgfr2 does not affect cardiac development, whereas the loss of Pdgfra prevents the differentiation of epicardium-derived cells into mature fibroblasts. Epicardial expression of a stabilized version of Ctnnb1 results in the formation of hyperproliferative epicardial cell clusters; epicardial expression of a constitutively active version of Smo leads to epicardial thickening and loss of epicardial mobilization. Canonical Wnt-, Hh-, and Fgfr1/Fgfr2-signalling are dispensable for epicardial development, but Pdgfra-signalling is crucial for the differentiation of cardiac fibroblasts from epicardium-derived cells.
The role of gender within the "stop smoking" program
Authors: Manuela Stoleru
Journal: European Respiratory Journal (2012)

Introduction   Understanding individual differences in smoking behavior and addiction to nicotine can increase knowledge in the development of therapy, influence the outcomes of treatment and is a challenge for developers.   Objective   The purpose of our study was to evaluate the role of sex in the effectiveness of smoking cessation to the National Romanian Program.   Methods and material   It is a study of a sample of 306 smokers from 01/07/2008 to 31/12/2009 interested to stop smoking. They were assessed on the age, sex, domicile, the level of CO expire, test Fagerstrom, the family situation, the type of tobacco and the amount for a maximum period of 12 weeks. First line treatments include Nicotinic substitutes, the bupropion and varenicline.   Results   We evaluate 216 (70.58 %) male, the average age was 43.72 years SD 13.5 95% CI 41 92-45. 53, smoking 30.90 PA comparative with 91 of women age 40.53 average SD 11.8 95% CI-38.06 43.01 who smoke 15.66 PA medium, SD 11.9 95% CI = 14 87 - 19.64. Men also started smoking earlier and had high dependence on nicotine than women. There is not a clear difference in the Fagerstrom test: TF = 5.85 for women TF = 5.62 for man.  The costs were almost equally distributed between the two categories.  There are no significant differences in looking at marital status: 76.92% comparative married women with 77.77% men. In both categories, the therapeutic attitude is dominated by the Champix 65.93% men to 51.38 % women. At the end of the treatment, were abstinent 40.65% women and 47.68% men.   Conclusion   Sex does not appear to be a predictive factor of cessation in treated individuals persons. Analyses of individual differences should focus on the identification of the processes that control the smoking behavior.
A COMPARISON OF PHENOXYPROPAZINE AND AMYTRYPTILINE IN DEPRESSION
Authors: J. T. ROSE, M. R. LEAHY, R. PLOWMAN
Journal: American Journal of Psychiatry (1963)

Phenoxypropazine is compared with amitryptiline in the treatment of 78 hospitalised patients suffering from primary depressive disorders. Most patients on either drug responded well, there being no significant difference in outcome between the 2 drug groups. Endogenous and reactive depressions showed no difference in response to phenoxypropazine. Side effects were few and did not interfere with treatment. It is considered that phenoxypropazine is a useful antidepressant of equal effectiveness to amitryptiline.
The effect of growth hormone therapy, adenotonsillectomy and genotype on obstructive sleep apnea in children with Prader-Willi syndrome
Authors: Helena Larramona Carrera, Neus Roca Saladrigues, Joan Carles Oliva, Roser Rosell, Raquel Corripio, Elisabeth Gabau
Journal: European Respiratory Journal (2013)

Objective: To review the effect of growth hormone (GH) therapy, adenotonsillectomy (AT) and genotype on obstructive sleep apnea (OSA) in children with Prader-Willi syndrome (PWS). Methods: Retrospective review of children (lt]18 years) with PWS referral to our institution. Polysomnograms were scored by American Academy of Sleep Medicine pediatric rules. For comparisons of age, body mass index and polysomnographic variables between pre- and post GH therapy and pre- and post- AT, Wilcoxon and Mann Whitney U tests were used. For comparisons of genotype and presence of OSA defined as an apnea hipopnea index (AHI)≥2/h, Pearson’s chi-squared test was used. Results: Twenty-one children with diagnosis of PWS were evaluated, 16 had a diagnosis of OSA. 8 and 5 children had a polysomnograms before and after initiation GH therapy and before and after AT, respectively. There were no significant changes in AHI before and after initiation GH therapy (p=0.6). Of note, 5 children increased AHI and 3 decreased (range -8 to 9.55). Although there were no differences between AHI pre and post-AT (p=0.2), AHI improved in 4 patients and 1 worsened. No differences were observed between genotype (deletion, uniparental disomy and imprinting defects) and OSA (p= 0.3). However, higher percentage of OSA was observed in deletion than uniparental disomy mutation (83.3% vs. 62.5%).Conclusions: Although no differences in OSA before and after GH therapy and AT could be demonstrated in children with PWS, some of them showed a worsening after GH therapy and no resolution post-AT. Our findings highlight individual assesment with sleep studies in the management of children with PWS.
Epicardial-Derived Cell Epithelial-to-Mesenchymal Transition and Fate Specification Require PDGF Receptor Signaling
Authors: Christopher L. Smith, Seung Tae Baek, Caroline Y. Sung, Michelle D. Tallquist
Journal: Circulation Research (2011)

In early heart development, platelet-derived growth factor (PDGF) receptor expression in the heart ventricles is restricted to the epicardium. Previously, we showed that PDGFRβ is required for coronary vascular smooth muscle cell (cVSMC) development, but a role for PDGFRα has not been identified. Therefore, we investigated the combined and independent roles of these receptors in epicardial development.To understand the contribution of PDGF receptors in epicardial development and epicardial-derived cell fate determination.By generating mice with epicardial-specific deletion of the PDGF receptors, we found that epicardial epithelial-to-mesenchymal transition (EMT) was defective. Sox9, an SRY-related transcription factor, was reduced in PDGF receptor-deficient epicardial cells, and overexpression of Sox9 restored epicardial migration, actin reorganization, and EMT gene expression profiles. The failure of epicardial EMT resulted in hearts that lacked epicardial-derived cardiac fibroblasts and cVSMC. Loss of PDGFRα resulted in a specific disruption of cardiac fibroblast development, whereas cVSMC development was unperturbed.Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial-mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates.
Loss of Bmx Nonreceptor Tyrosine Kinase Prevents Pressure Overload–Induced Cardiac Hypertrophy
Authors: Scherise A. Mitchell-Jordan, Tanja Holopainen, Shuxun Ren, Sujing Wang, Sarah Warburton, Michael J. Zhang, Kari Alitalo, Yibin Wang, Thomas M. Vondriska
Journal: Circulation Research (2008)

Bmx nonreceptor tyrosine kinase has an established role in endothelial and lymphocyte signaling; however, its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx knockout mice) to transverse aortic constriction (TAC). In comparison with wild-type mice, which progressively developed massive hypertrophy following TAC, Bmx knockout mice were resistant to TAC-induced cardiac growth at the organ and cell level. Loss of Bmx preserved cardiac ejection fraction and decreased mortality following TAC. These findings are the first to demonstrate a necessary role for the Tec family of tyrosine kinases in the heart and reveal a novel regulator (Bmx) of pressure overload-induced hypertrophic growth.
Lentiviral Overexpression of GRK6 Alleviates <scp>l</scp> -Dopa–Induced Dyskinesia in Experimental Parkinson’s Disease
Authors: Mohamed R. Ahmed, Amandine Berthet, Evgeny Bychkov, Gregory Porras, Qin Li, Bernard H. Bioulac, Yonatan T. Carl, Bertrand Bloch, Seunghyi Kook, Incarnation Aubert, Sandra Dovero, Evelyne Doudnikoff, Vsevolod V. Gurevich, Eugenia V. Gurevich, Erwan Bezard
Journal: Science Translational Medicine (2010)

G protein–coupled receptor kinase 6, which promotes desensitization of the dopamine receptor, alleviates dyskinesia without compromising the antiparkinsonian effect of l -dopa.
Prognostic Value and Function of KLF4 in Prostate Cancer: RNAa and Vector-Mediated Overexpression Identify KLF4 as an Inhibitor of Tumor Cell Growth and Migration
Authors: Ji Wang, Robert F. Place, Vera Huang, Xiaoling Wang, Emily J. Noonan, Clara E. Magyar, Jiaoti Huang, Long-Cheng Li
Journal: Cancer Research (2010)

Abstract KLF4/GLKF4 is a transcription factor that can have divergent functions in different malignancies. The role of KLF4 in prostate cancer etiology remains unclear. We have recently reported that small double-stranded RNA can induce gene expression by targeting promoter sequence in a phenomenon referred to as RNA activation (RNAa). In this study, we examine KLF4 levels in prostate cancer tissue and utilize RNAa as a tool for gene overexpression to investigate its function. Expression analysis indicated that KLF4 is significantly downregulated in prostate cancer cell lines compared with nontumorigenic prostate cells. Meta-analysis of existing cDNA microarray data also revealed that KLF4 is frequently depleted in prostate cancer tissue with more pronounced reduction in metastases. In support, tissue microarray analysis of tumors and patient-matched controls indicated downregulation of KLF4 in metastatic tumor samples. Logistic regression analysis found that tumors with a KLF4 staining score less than 5 had a 15-fold higher risk for developing metastatic prostate cancer (P = 0.001; 95% confidence interval, 3.0–79.0). In vitro analysis indicated that RNAa-mediated overexpression of KLF4 inhibited prostate cancer cell proliferation and survival and altered the expression of several downstream cell-cycle–related genes. Ectopic expression of KLF4 via viral transduction recapitulated the RNAa results, validating its inhibitory effects on cancer growth. Reactivation of KLF4 also suppressed migration and invasion of prostate cancer cells. These results suggest that KLF4 functions as an inhibitor of tumor cell growth and migration in prostate cancer and decreased expression has prognostic value for predicting prostate cancer metastasis. Cancer Res; 70(24); 10182–91. ©2010 AACR.