tbuckley/cabot-search huggingface dataset:
Computational significance of the cellular mechanisms for synaptic plasticity in Purkinje cells
Authors: James C. Houk, Simon Alford
Journal: Behavioral and Brain Sciences (1996)

The data on the cellular mechanism of LTD that is presented in four target articles is synthesized into a new model of Purkinje cell plasticity. This model attempts to address credit assignment problems that are crucial in learning systems. Intracellular signal transduction mechanisms may provide the mechanism for a 3-factor learning rule and a trace mechanism. The latter may permit delayed information about motor error to modify the prior synaptic events that caused the error. This model may help to focus future cellular studies on issues that are particularly critical for a computationally viable concept of cerebellar plasticity, [CRÉPEL et al.; HOUK et al.; KANO; LINDEN; VINCENT]
Modern Approaches to Treating Acute Promyelocytic Leukemia
Authors: Miguel A. Sanz, Francesco Lo-Coco
Journal: Journal of Clinical Oncology (2011)

The advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the antileukemic efficacy in acute promyelocytic leukemia (APL), leading to complete remission rates greater than 90%, virtual absence of resistance, and cure rates of nearly 80%. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (ie, those presenting with WBC > 10 × 10(9)/L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. In this review article, we discuss most recent advances in the treatment of patients with newly diagnosed and relapsed APL.
The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding
Authors: Xiao-Yong Li, Sean Thomas, Peter J Sabo, Michael B Eisen, John A Stamatoyannopoulos, Mark D Biggin
Journal: Genome biology (2011)

In Drosophila embryos, many biochemically and functionally unrelated transcription factors bind quantitatively to highly overlapping sets of genomic regions, with much of the lowest levels of binding being incidental, non-functional interactions on DNA. The primary biochemical mechanisms that drive these genome-wide occupancy patterns have yet to be established.Here we use data resulting from the DNaseI digestion of isolated embryo nuclei to provide a biophysical measure of the degree to which proteins can access different regions of the genome. We show that the in vivo binding patterns of 21 developmental regulators are quantitatively correlated with DNA accessibility in chromatin. Furthermore, we find that levels of factor occupancy in vivo correlate much more with the degree of chromatin accessibility than with occupancy predicted from in vitro affinity measurements using purified protein and naked DNA. Within accessible regions, however, the intrinsic affinity of the factor for DNA does play a role in determining net occupancy, with even weak affinity recognition sites contributing. Finally, we show that programmed changes in chromatin accessibility between different developmental stages correlate with quantitative alterations in factor binding.Based on these and other results, we propose a general mechanism to explain the widespread, overlapping DNA binding by animal transcription factors. In this view, transcription factors are expressed at sufficiently high concentrations in cells such that they can occupy their recognition sequences in highly accessible chromatin without the aid of physical cooperative interactions with other proteins, leading to highly overlapping, graded binding of unrelated factors.
Survival of patients with a strongly positive exercise electrocardiogram.
Authors: G R Dagenais, J R Rouleau, A Christen, J Fabia
Journal: Circulation (1982)

To assess the prognosis of patients with a strongly positive exercise ECG, the 5-year cumulative survival rate was computed for 220 medically treated patients. Of these patients, 107 had coronary angiograms (group A) and 113 did not (group B). All had horizontal or downsloping ST depression greater than or equal to 2 mm during a multistage Bruce protocol treadmill exercise test. In group A, the overall 5-year survival rate was 74 +/- 5%. Survival decreased with decreasing duration of exercise: All patients who achieved stage IV (541 seconds or more) survived, whereas the survival rate was 86 +/- 6% when the patients terminated their exercise during stage III (361 - 540 seconds), 73 +/- 7% when during stage II (181 - 360 seconds) and only 52 +/- 13% when during stage I (180 seconds or less). The mortality was associated with more severe coronary artery disease, and sudden death was the main cause of death. Patients in group B had a longer mean exercise duration than those in group A and, as expected, a higher survival rate (91 +/- 3%, p less than 0.01), which also varied according to the exercise duration. Among patients with a strongly positive exercise ECG, the duration of exercise identifies subsets that have different survival rates.
P163 Effects of Socio–Economic Status on Lung Cancer Stage and Mortality – North-West Perspective: Abstract P163 Table 1
Authors: S Gudur, V Patel, R Sundar, I Aziz, A Ashish
Journal: Thorax (2012)

<h3>Background</h3> Lung cancer prevalence and mortality has been shown to be higher in the lower socio-economic group in England and Wales.<sup>1</sup> Northwest of England has one of the highest density of economically deprived regions in the country. Our institution caters to a population of approximately 330,000 in one of the poorest regions of Northwest England. We aimed to analyse the effect of socio–economic status on lung cancer staging on presentation and mortality in our patient cohort. <h3>Methods</h3> All patients with newly diagnosed lung cancer patients between 1st Jan–31st Dec 2011 were included in this cross sectional study. Patient data was accessed from our local lung cancer database. Deprivation score as detailed by index of multiple deprivation (IMD) of our cohort were obtained from the local council. <h3>Results</h3> Our socioeconomic postcodes showed that there were no patients from the top 10<sup>th</sup> centile postcodes of the country in our catchment. However, 37% (93) were in the lowest 20<sup>th</sup> centile compared to 20% nationally <sup>(2).</sup> The disease staging and mortality for top and bottom quartiles is shown in Table 1. Of 249 patients, 113 (45%) were females. Mean age was 72.4 years (Range 40–97). On diagnosis, 57 (23%) patients had stage 3 and 139 (56%) had stage 4 disease. 162 (65%) of patients died with an average survival after diagnosis of only 62 days (range 31.25– 148.5 days). <h3>Conclusions</h3> No significant differences were noted in lung cancer incidence or mortality across socio-economic ends in our local population. Noticeably, there was a high incidence of patients with extensive stage cancer reflecting high mortality. This late presentation may be a reflection of poor health awareness amongst our deprived population belt. A longer study may give us an idea of which areas to target for further education and improvement. <h3>References</h3> UK Lung cancer registry, 2011. Cancer incidence and mortality, Office for National Statistics.
A comparison of narrow band phototherapy (TL-01) and photochemotherapy (PUVA) in the management of polymorphic light eruption
Authors: D Bilsland, S A George, N K Gibbs, T Aitchison, B E Johnson, J Ferguson
Journal: British Journal of Dermatology (1993)

Twenty-five patients suffering from severe polymorphic light eruption (PLE) were randomized to either photochemotherapy (PUVA) or narrow-band phototherapy (TL-01 UVB) treatment in early spring; patients receiving UVB were given placebo tablets to achieve a matching therapy procedure. During the 4 months following treatment, patient exposure to solar UVB was monitored with polysulphone badges. PLE occurrence, severity, and restriction of outdoor activity were recorded, using weekly diary-sheets. Analysis of covariance on this data, using the logarithm of UVB exposure as the explanatory variable, showed no significant differences between the treatments. TL-01 UVB is an effective alternative to PUVA in the management of PLE.
The influence of demographic and socioeconomic factors on health-related quality of life in asthma
Authors: A J Apter, S T Reisine, G Affleck, E Barrows, R L ZuWallack
Journal: Journal of Allergy and Clinical Immunology (1999)

<h2>Abstract</h2> <b>Background:</b> Although health-related quality of life (HRQL) in asthma is strongly influenced by disease severity, demographic and socioeconomic variables may also be important factors. <b>Objective:</b> We related demographics, asthma severity, and socioeconomic factors to HRQL. <b>Methods:</b> We interviewed 50 patients with moderate or severe asthma recruited from outpatient health center–based clinics to determine demographics, socioeconomic status, asthma severity, medication use, and HRQL. For HRQL, the mean total score of the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short-Form 36 questionnaires physical and mental component summary scores (PCS and MCS, respectively) were used. <b>Results:</b> The mean patient age was 46 ± 14 years, and the FEV<sub>1</sub> was 75% ± 21% of predicted value. Twenty-nine subjects had been hospitalized for asthma, 29 belonged to a minority racial/ethnic group, and 16 had less than 12 years of education. The mean total AQLQ score was 4.12 ± 1.42, the PCS was 37 ± 10, and the MCS was 45 ± 13. In univariate analyses, severity (nighttime awakenings, prednisone use, and a history of emergency department visits), racial/ethnic group (African American, white, or Hispanic), and socioeconomic status (low educational level, unemployed, family income under $20,000, public assistance, or no health insurance) were related to HRQL. These factors explained 67% of the variance of AQLQ and 48% of the variance of the PCS. Much of the quality of life variance was shared among these variables. Explanatory variables were not related to MCS in multivariate analysis. <b>Conclusion:</b> Socioeconomic status is an additional important independent factor influencing HRQL in asthma. In this study it was difficult to separate out the unique effects of socioeconomic status and race/ethnicity. (J Allergy Clin Immunol 1999;103:72-8.)
Explanations for the Lower Rates of Diabetic Neuropathy in Indian Asians Versus Europeans
Authors: Caroline A. Abbott, Nishi Chaturvedi, Rayaz A. Malik, Eleanna Salgami, Allen P. Yates, Philip W. Pemberton, Andrew J.M. Boulton
Journal: Diabetes Care (2010)

OBJECTIVE Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (−0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO2) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37–0.93]; P = 0.02) and was primarily accounted for by better TCpO2 (0.70 [0.40–1.21]; P = 0.2). CONCLUSIONS Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk.
Hypereosinophilic Syndrome: Current Approach to Diagnosis and Treatment
Authors: Amy Klion
Journal: Annual Review of Medicine (2009)

Hypereosinophilic syndrome is a heterogeneous group of rare disorders characterized by marked blood or tissue eosinophilia resulting in a wide variety of clinical manifestations. Although the existence of clinical subtypes (or variants) of HES has been appreciated for some time, the recent characterization of some of these variants at the molecular and immunologic levels has demonstrated dramatic differences in disease pathogenesis, response to treatment, and prognosis depending on the etiology of the eosinophilia. This, together with the availability of novel targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, has fundamentally altered the approach to the diagnosis and treatment of HES.
Endotoxaemia and complement activation in acute pancreatitis in man.
Authors: A K Foulis, W R Murray, D Galloway, A C McCartney, E Lang, J Veitch, K Whaley
Journal: Gut (1982)

Twenty-four patients who experienced 26 attacks of acute pancreatitis were studied. Endotoxaemia, as measured by the limulus lysate assay, was present in 13 of the attacks. Six out of seven patients with systemic complications of the disease had endotoxaemia. C3 catabolism was increased in all 26 attacks of pancreatitis, and a falling level of C3 during attacks of severe pancreatitis was associated with a fatal outcome. There was statistical evidence of more complement activation in serum samples taken when patients had positive limulus lysate tests than when endotoxin was not detected in their blood.
Evaluating the “Leeds criteria” for<i>Pseudomonas aeruginosa</i>infection in a cystic fibrosis centre
Authors: M. Proesmans, W. Balinska-Miskiewicz, L. Dupont, X. Bossuyt, J. Verhaegen, N. Høiby, K. de Boeck
Journal: European Respiratory Journal (2006)

Four separate categories of chronic Pseudomonas aeruginosa (Pa) infection in children with cystic fibrosis (CF) have been previously defined, based on airway cultures taken over the previous year. The aim of the present study was to evaluate this definition in the current authors' paediatric and adult CF clinic using clinical, immunological and lung function parameters. During follow-up, out of 193 patients, 55 (34%) CF patients had never been infected with Pa, 27 (17%) were free of Pa, 29 (18%) were intermittently infected and 51 (31%) were chronically infected. Disease severity markers, such as lung function, were significantly worse in the chronic group, especially in the paediatric population. Differences in adult patients were smaller and no longer significant. Pa antibodies differed strongly between the groups, and were very high (mean+/-sd 55.4+/-5.5) and highly statistically significant from all other groups in the chronic group. They were low and different from all other groups in the never group (1.8+/-0.6). Pa antibodies did not differ between the free of Pa and the intermittent group. In conclusion, the current authors confirmed an agreement between Pseudomonas aeruginosa status according to the new definition and clinical status, as well as with the level of Pseudomonas aeruginosa antibodies.
Allogeneic Peripheral Blood Stem-Cell Compared With Bone Marrow Transplantation in the Management of Hematologic Malignancies: An Individual Patient Data Meta-Analysis of Nine Randomized Trials
Journal: Journal of Clinical Oncology (2005)

Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies.
Inhaled corticosteroid use in young children at high risk of asthma
Authors: L E R McLure
Journal: Thorax (2006)

▴ Guilbert WT, Morgan WJ, Zeiger RS, et al . Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med2006;354:1985–7[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The PEAK (Prevention of Early Asthma in Kids) clinical trial tested the hypothesis that the natural history of wheezing in early life may be altered by the continuous … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DGuilbert%26rft.auinit1%253DT.%2BW.%26rft.volume%253D354%26rft.issue%253D19%26rft.spage%253D1985%26rft.epage%253D1997%26rft.atitle%253DLong-term%2Binhaled%2Bcorticosteroids%2Bin%2Bpreschool%2Bchildren%2Bat%2Bhigh%2Brisk%2Bfor%2Basthma.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa051378%26rft_id%253Dinfo%253Apmid%252F16687711%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa051378&link_type=DOI [3]: /lookup/external-ref?access_num=16687711&link_type=MED&atom=%2Fthoraxjnl%2F61%2F8%2F698.atom [4]: /lookup/external-ref?access_num=000237413100003&link_type=ISI
Transforming Growth Factor-β–Induced Inhibition of Myogenesis Is Mediated Through Smad Pathway and Is Modulated by Microtubule Dynamic Stability
Authors: Shoukang Zhu, Pascal J. Goldschmidt-Clermont, Chunming Dong
Journal: Circulation Research (2004)

The expression of muscle-specific genes associated with myogenesis is controlled by several myogenic transcription factors, including myogenin and MEF2D. Transforming growth factor-beta (TGF-beta) has been shown to inhibit myogenesis, yet the molecular mechanisms underlying such inhibition are not known. In the present study, TGF-beta was shown to inhibit myogenin and MEF2D expression and myotube formation in C2C12 myoblasts cultured in differentiation medium in a cell density-dependent manner. Transfection of C2C12 cells with Smad7, an antagonist for TGF-beta/Smad signaling, restored the capacity of these cells to differentiate in the presence of TGF-beta or when cultured in growth medium at low confluence, conditions that hinder muscle differentiation. Moreover, nocodazole, a microtubule-destabilizing agent, enhanced the inhibition of myogenesis exerted by TGF-beta, an effect that could be restored by tubulin-polymerizing agent taxol, both of which have been shown to affect Smad-microtubule interaction and regulate TGF-beta/Smad signaling. Our results indicate that TGF-beta inhibits myogenesis, at least in part, via Smad pathway, and provide evidence that low-dose pharmacological agents taxol and nocodazole can be used as a means to modulate myogenesis without affecting cell survival.
Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer
Authors: Mark A. Socinski, Egbert F. Smit, Paul Lorigan, Kartik Konduri, Martin Reck, Aleksandra Szczesna, Johnetta Blakely, Piotr Serwatowski, Nina A. Karaseva, Tudor Ciuleanu, Jacek Jassem, Mircea Dediu, Shengyan Hong, Carla Visseren-Grul, Axel-Rainer Hanauske, Coleman K. Obasaju, Susan C. Guba, Nick Thatcher
Journal: Journal of Clinical Oncology (2009)

Purpose Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Patients and Methods Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m 2 on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m 2 on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. Results Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P &lt; .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P &lt; .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P &lt; .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. Conclusion Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.
Extranuclear Steroid Receptors: Nature and Actions
Authors: Stephen R. Hammes, Ellis R. Levin
Journal: Endocrine Reviews (2007)

Rapid effects of steroid hormones result from the actions of specific receptors localized most often to the plasma membrane. Fast-acting membrane-initiated steroid signaling (MISS) 1leads to the modification of existing proteins and cell behaviors. Rapid steroid-triggered signaling through calcium, amine release, and kinase activation also impacts the regulation of gene expression by steroids, sometimes requiring integration with nuclear steroid receptor function. In this and other ways, the integration of all steroid actions in the cell coordinates outcomes such as cell fate, proliferation, differentiation, and migration. The nature of the receptors is of intense interest, and significant data suggest that extranuclear and nuclear steroid receptor pools are the same proteins. Insights regarding the structural determinants for membrane localization and function, as well as the nature of interactions with G proteins and other signaling molecules in confined areas of the membrane, have led to a fuller understanding of how steroid receptors effect rapid actions. Increasingly, the relevance of rapid signaling for the in vivo functions of steroid hormones has been established. Examples include steroid effects on reproductive organ development and function, cardiovascular responsiveness, and cancer biology. However, although great strides have been made, much remains to be understood concerning the integration of extranuclear and nuclear receptor functions to organ biology. In this review, we highlight the significant progress that has been made in these areas.
Response to Letters Regarding Article, “Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction”
Authors: Michael R. Zile, Catalin F. Baicu, John S. Gottdiener, Scott J. Hetzel, John J. McMurray, Michel Komajda, Robert McKelvie, Barry M. Massie, Peter E. Carson
Journal: Circulation (2012)