tbuckley/cabot-search huggingface dataset:
Endoscopic (oesophageal) ultrasound guided fine needle aspiration (EUS-FNA)
Authors: C M Richardson
Journal: Thorax (2004)

A new tool in lung cancer staging

The management of lung cancer depends to a great extent on its histological type and the stage of disease. Although most patients with non-small cell lung cancer (NSCLC) have advanced disease at presentation, approximately 30% have tumour confined to the lung and locoregional lymph nodes. For these patients surgery offers the best hope of a cure. Despite apparent complete resection, 5 year survival rates after surgery are approximately 40–50%.1 This highlights the importance of accurately staging lung cancer to determine resectability and provide prognostic information.

In clinical practice a presumptive diagnosis and stage are based on presentation, risk factors, and radiological appearances—particularly CT scans. Obtaining a histological diagnosis and confirming the stage of the disease often take place at the same time. One of the most difficult tasks is accurate staging of nodal involvement in the mediastinum.

It is reported that mediastinal lymph nodes contain metastatic disease in 28–38% of patients with NSCLC at the time of diagnosis.2 Traditionally, CT scanning has been used to assess mediastinal lymph node involvement. Lymph nodes greater than 1 cm in short axis diameter are considered abnormal and suggest involvement. However, CT detection of lymph node spread has sensitivity and specificity rates of 61% and 79%, respectively.3 Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) is more accurate in identifying mediastinal lymph node involvement. FDG-PET in combination with CT scanning has been shown to further improve sensitivity and specificity rates in detecting lymph node involvement,3 but in much of …
Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer
Authors: Arlene A. Forastiere, Qiang Zhang, Randal S. Weber, Moshe H. Maor, Helmuth Goepfert, Thomas F. Pajak, William Morrison, Bonnie Glisson, Andy Trotti, John A. Ridge, Wade Thorstad, Henry Wagner, John F. Ensley, Jay S. Cooper
Journal: Journal of Clinical Oncology (2012)

Purpose To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and Methods Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Results Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P &lt; .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). Conclusion These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.
Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pT3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO 96-02/AUO AP 09/95
Authors: Thomas Wiegel, Dirk Bottke, Ursula Steiner, Alessandra Siegmann, Reinhard Golz, Stephan Störkel, Norman Willich, Axel Semjonow, Rainer Souchon, Michael Stöckle, Christian Rübe, Lothar Weißbach, Peter Althaus, Udo Rebmann, Tilman Kälble, Horst Jürgen Feldmann, Manfred Wirth, Axel Hinke, Wolfgang Hinkelbein, Kurt Miller
Journal: Journal of Clinical Oncology (2009)

Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.
Anti-fibrotic effects of liver X receptor agonists in human fetal lung fibroblasts
Authors: Shu Hisata, Shigeki Chiba, Takafumi Ito, Masahito Ebina, Toshihiro Nukiwa
Journal: European Respiratory Journal (2011)

Introduction: Idiopathic pulmonary fibrosis is a progressive life-threatening disease for which anti-inflammatory agents such as glucocorticoids have no therapeutic effect. Liver X receptors (LXRs), which are nuclear receptors activated by oxysterols as natural ligands, show similar tissue-distribution patterns with glucocorticoid receptor and peroxisome proliferator-activated receptor (PPAR)-γ. LXRs play important roles not only in cholesterol metabolism and triglyceride synthesis, but also in inflammation and innate immunity. Previous studies showed anti-fibrotic effects of PPARγ agonists, but it remains unknown whether LXR agonists have anti-fibrotic abilities.

Aims: The aim of our current study is to analyze anti-fibrotic effects of LXR agonists on human lung fibroblast.

Methods: Serum-deprived MRC5 cells (human fetal lung fibroblast cell line) were pre-incubated with synthetic LXR agonist T0901317 and natural agonist 22(R)-hydroxycholesterol, and were differentiated into myofibroblasts by TGF-β1 for 48 hours. Changes in α-smooth muscle actin (α-SMA) and phosphorylated-Smad2/3 were analyzed by western blot. The inhibitory effects of irreversible PPARγ antagonist GW-9662 on anti-fibrotic abilities of LXR agonists were also examined.

Results: LXR agonist T0901317 and 22(R)-hydroxycholesterol inhibited TGF-β1-driven myofibroblast-differentiation as determined by α-SMA by western blot. T0901317 did not inhibit Smad2/3 phosphorylation. An irreversible PPARγ antagonist GW-9662 did not reverse the inhibition of myofibroblast-differentiation by T0901317.

Conclusion: LXR agonists have novel and potent anti-fibrotic effects in human lung fibroblasts.
How brains make chaos in order to make sense of the world
Authors: Christine A. Skarda, Walter J. Freeman
Journal: Behavioral and Brain Sciences (1987)

Abstract Recent “connectionist” models provide a new explanatory alternative to the digital computer as a model for brain function. Evidence from our EEG research on the olfactory bulb suggests that the brain may indeed use computational mechanisms like those found in connectionist models. In the present paper we discuss our data and develop a model to describe the neural dynamics responsible for odor recognition and discrimination. The results indicate the existence of sensory- and motor-specific information in the spatial dimension of EEG activity and call for new physiological metaphors and techniques of analysis. Special emphasis is placed in our model on chaotic neural activity. We hypothesize that chaotic behavior serves as the essential ground state for the neural perceptual apparatus, and we propose a mechanism for acquiring new forms of patterned activity corresponding to new learned odors. Finally, some of the implications of our neural model for behavioral theories are briefly discussed. Our research, in concert with the connectionist work, encourages a reevaluation of explanatory models that are based only on the digital computer metaphor.
Availability of inpatient beds for psychiatric admissions in the NHS
Authors: S. Weich
Journal: BMJ (2008)

Is decreasing, and care is expensive, unpopular, and often unsatisfactory

How we commission, deliver, and regulate mental health care has changed dramatically in the past 14 years, but much of what Thornicroft and Strathdee wrote in their 1994 BMJ editorial, “How many psychiatric beds?,” still rings true.1 We are asking the same question today, because inpatient care still accounts for two thirds of the budget of NHS mental health services.2 Despite a phenomenal revolution in mental health services,3 the answer lies outside inpatient units rather than within them.2 3 4 5 6 

In the linked study, Keown and colleagues (doi:10.1136/bmj.a1837) perform a retrospective analysis of voluntary and involuntary psychiatric admissions in England between 1996 and 2006.7 They find that the total number of involuntary admissions (detentions under the Mental Health Act) each year increased by 20%, with a threefold increase in the likelihood of admission to a private facility. People who had been admitted involuntarily occupied 23% of NHS psychiatric beds in 1996 but 36% in 2006. When measured against population size, there was a reduction from 96 to 66 beds per …
Peroxisome proliferator-activated receptor γ (PPARγ) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer
Authors: Jo A. Van Ginderachter, Sofie Meerschaut, Yuanqing Liu, Lea Brys, Kurt De Groeve, Gholamreza Hassanzadeh Ghassabeh, Geert Raes, Patrick De Baetselier
Journal: Blood (2006)
Determinants of Androgen Deprivation Therapy Use for Prostate Cancer: Role of the Urologist
Authors: Vahakn B. Shahinian, Yong-Fang Kuo, Jean L. Freeman, James S. Goodwin
Journal: JNCI Journal of the National Cancer Institute (2006)

The use of androgen deprivation therapy for prostate cancer has been increasing, even in settings for which there is weak or no evidence of efficacy. This pattern suggests that factors other than the typical patient and tumor characteristics may be driving its use. We assessed the importance of the physician as a determinant of the use of androgen deprivation therapy in prostate cancer in a population-based, retrospective cohort study using the Surveillance, Epidemiology and End-Results-Medicare linked database.Participants included 61 717 men with incident prostate cancer diagnosed from January 1, 1992, through December 31, 1999, and 1802 urologists providing care to them within 1 year of cancer diagnosis. Multilevel analyses were used to estimate and partition the variance in use of androgen deprivation therapy within 6 months of diagnosis between patient or tumor characteristics and urologist to examine the relative contribution of each component to androgen deprivation therapy.The percentage of the total variance in the use of androgen deprivation therapy attributable to the urologist was consistently higher than that attributable to tumor or patient characteristics. This pattern was most pronounced for patients diagnosed from January 1, 1997, through December 31, 1999, in which 22.56% of the total variance in use of androgen deprivation therapy was attributable to the urologist, 9.71% to tumor characteristics (stage or grade), and 4.29% to patient characteristics (age, ethnicity, socio-economic status, comorbidity, geographic region, or year of diagnosis).Which urologist a patient sees may be more important in determining whether they will receive androgen deprivation therapy than tumor or patient characteristics.
Comparison of etiology and resistance in respiratory isolates of AIDS patients vs. non-AIDS patients in South Sudan and Kenya
Authors: V. Sladeckova, L. Fabianova, A. Kolenova, D. Horvathova, Z. Kniezova, A. Doczeova, M. Taziarova, J. Benca, M. Bartkoviak, S. Seckova, A. Liskova, P. Beno, O. Babelova, V. Krcmery
Journal: Journal of Infection (2006)
Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis
Authors: Gaël Debauve, Denis Nonclercq, Fabrice Ribaucour, Murielle Wiedig, Cécile Gerbaux, Oberdan Leo, Guy Laurent, Fabrice Journé, Alexandra Belayew, Gérard Toubeau
Journal: Molecular Cancer (2006)

Abstract Background The Helicase-Like Transcription Factor (HLTF/SMARCA3) belongs to the family of SWI/SNF proteins that use the energy of ATP hydrolysis to remodel chromatin in a variety of cellular processes. Several SWI/SNF genes are disrupted in cancer, suggesting a role of tumor suppressor. Similarly, the HLTF gene was recently found to be inactivated by hypermethylation in a number of advanced colon and gastric tumors. However, other evidences indicated a 20-fold HLTF overexpression in cell lines derived from various neoplasms (ovary, breast, cervix, kidney...). Results In the present study, we investigated HLTF expression by immunohistochemistry in a model of kidney tumors induced by continuous administration of diethylstilbestrol to male Syrian golden hamsters. A strong labeling was already detected in small tumor buds, making HLTF an early cancer marker in this model. Although every cell stained for HLTF at this early stage, the number of HLTF-positive cells decreased to 10% with cancer progression, and these positive cells were dispersed in the tumor mass. HLTF expression was conserved in the HKT-1097 cell line established from kidney tumors, but again only 10% of positive cells were found in xenografts produced by HKT-1097 cells in nude mice. Conclusion In conclusion, our data suggest that HLTF gene activation is linked to initial steps of carcinogenesis in this model and should be investigated in early stages of other neoplasms.
Molecular Mechanisms Underlying FIP1L1-PDGFRA–Mediated Myeloproliferation
Authors: Miranda Buitenhuis, Liesbeth P. Verhagen, Jan Cools, Paul J. Coffer
Journal: Cancer Research (2007)

An interstitial deletion on chromosome 4q12 resulting in the formation of the FIP1L1-PDGFRA fusion protein is involved in the pathogenesis of imatinib-sensitive chronic eosinophilic leukemia. The molecular mechanisms underlying the development of disease are largely undefined. Human CD34(+) hematopoietic progenitor cells were used to investigate the role of FIP1L1-PDGFRA in modulating lineage development. FIP1L1-PDGFRA induced both proliferation and differentiation of eosinophils, neutrophils, and erythrocytes in the absence of cytokines, which could be inhibited by imatinib. Whereas expression of FIP1L1-PDGFRA in hematopoietic stem cells and common myeloid progenitors induced the formation of multiple myeloid lineages, expression in granulocyte-macrophage progenitors induced only the development of eosinophils, neutrophils, and myeloblasts. Deletion of amino acids 30 to 233 in the FIP1L1 gene [FIP1L1(1-29)-PDGFRA] gave rise to an intermediate phenotype, exhibiting a dramatic reduction in the number of erythrocytes. FIP1L1-PDGFRA and FIP1L1(1-29)-PDGFRA both induced the activation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) in myeloid progenitors, whereas signal transducers and activators of transcription 5 (STAT5) and protein kinase B/c-akt were only activated by FIP1L1-PDGFRA. Dominant-negative STAT5 partially inhibited FIP1L1-PDGFRA-induced colony formation, whereas combined inhibition of phosphatidylinositol-3-kinase and ERK1/2 significantly reversed FIP1L1-PDGFRA-induced colony formation. Taken together, these results suggest that expression of FIP1L1-PDFGRA in human hematopoietic progenitors induce a myeloproliferative phenotype via activation of multiple signaling molecules including phosphatidylinositol-3-kinase, ERK1/2, and STAT5.
Self-report instruments for assessing sleep dysfunction in an adult traumatic brain injury population: A systematic review
Authors: Tatyana Mollayeva, Tetyana Kendzerska, Angela Colantonio
Journal: Sleep Medicine Reviews (2013)

To review the number and characteristics of self-reported sleep measures used to evaluate impaired sleep/wakefulness in traumatic brain injury (TBI) populations.We conducted a comprehensive peer-reviewed literature search of Medline, Embase, PsycINFO, CINAHL, and various bibliographies. Only standardized self-report measures for evaluating sleep dysfunction and its signs were taken into consideration.Sixteen self-report measures used in TBI research and clinical practices were identified. Five were generic, five symptom-related, and six were condition-specific measures. The Pittsburgh sleep quality index and Epworth sleepiness scale were partially validated in post-acute TBI.Although no instrument has been specifically developed for TBI patients, there are scientific benefits to using the existing measures. However, additional research is needed to examine their applicability to the TBI population. The design and introduction of a new instrument able to triage sleep-related complaints between depressive, other medical, and primary sleep disorders-with a section for caregiver reports-might assist in the identification of the etiology of sleep dysfunction in persons with TBI. In choosing or developing a sleep measure, researchers and clinicians must consider the specific domains they want to screen, diagnose, or monitor. Polysomnography is recommended for diagnosing specific sleep disorders that cannot be diagnosed solely using a self-report measure.
P118Cardiac arrhythmia induced by genetic silencing of funny (f) channels is rescued by Girk4 inactivation
Authors: P Mesirca, J Alig, AG Torrente, A Rollin, A Vincent, S Dubel, A Fernandez, A Seniuk, D Isbrandt, ME Mangoni
Journal: Cardiovascular Research (2014)

The mechanisms underlying heart automaticity are still poorly understood and controversial. Here we obtained, for the first time, complete conditional and time-controlled silencing of the hyperpolarization-activated "funny" current (If) by expression of a dominant-negative non-conductive human HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing recapitulated severe human disease of cardiac rhythm and conduction and showed that the functional role of f-channels in pacemaking critically depends on the activity of the autonomic nervous system. In line with this evidence, we were able to rescue failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice, without impairing heartbeat control. Our study establishes the role of f-channels in cardiac pacemaking and indicates that arrhythmia related to HCN loss-of-function in humans may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus indicating a new unexplored therapeutic strategy to treat heart rhythm diseases.
Current Histopathologic and Molecular Characterisations of Prostate Cancer: Towards Individualised Prognosis and Therapies
Authors: Matteo Santoni, Marina Scarpelli, Roberta Mazzucchelli, Antonio Lopez-Beltran, Liang Cheng, Jonathan I. Epstein, Stefano Cascinu, Alberto Briganti, James W. Catto, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2015)
New Perspectives in Monitoring Lung Inflammation: Analysis of Exhaled Breath Condensate
Authors: O. Holz
Journal: European Respiratory Journal (2005)

New Perspectives in Monitoring Lung Inflammation: Analysis of Exhaled Breath Condensate     Edited by Paolo Montuschi     CRC Press 2005; London, New York, Washington, DC     Pages: 218. ISBN: 0-415-32465-3

This book on exhaled breath condensate (EBC), edited by Paolo Montuschi, mirrors the large interest in a method, which promises a totally noninvasive way to assess airway inflammation.

It is of great relevance for those who decide to enter this field of research, as it provides an extensive review of the published literature as well as a critical view on open questions and methodological issues.

The book …
ESRD as a Window into America's Cost Crisis in Health Care
Authors: Felix Knauf, Peter S. Aronson
Journal: Journal of the American Society of Nephrology (2009)

The United States is facing a severe crisis over health care costs. Although nearly 15% of the population—some 45 million people—lack health insurance,1 per capita health care expenditures in the United States are approximately twice as high as in other industrialized countries,2 most of which provide near-universal health insurance coverage. Despite these high per capita health care expenditures, health outcomes in the United States are no better, and arguably significantly worse, than in these other countries.3 Moreover, because health care expenditures in the United States have been rising at a rate almost 3% faster than the economy as a whole over the past 30 yr, health care expenses have been absorbing an ever-increasing fraction of the gross domestic product (GDP).4 Even before the current severe recession, it had been estimated that if current trends continue, health care expenses would represent 30% of the GDP within 30 yr, and that the Medicare hospital insurance trust fund would be exhausted within a decade.5

Some have argued that the projected increase in health care expenditures to consume a higher and higher fraction of GDP is not necessarily a problem.6,7 After all, the health care industry itself is an important driving force of the economy and its growth creates new jobs. Moreover, as long as the economy as a whole enjoys sufficient growth, devoting an increasing share of GDP to health care need not reduce absolute spending in areas other than health care, and therefore need not reduce the standard of living. But now that it represents over one-sixth of the national economy, the inefficiency of the American health care system represents a grave threat to America's economic competitiveness. Again, it should be emphasized that per capita health care expenditures in the United States are twice …