tbuckley/cabot-search huggingface dataset:
GSK-3β Targets Cdc25A for Ubiquitin-Mediated Proteolysis, and GSK-3β Inactivation Correlates with Cdc25A Overproduction in Human Cancers
Authors: Tiebang Kang, Yongkun Wei, Yuchi Honaker, Hiroshi Yamaguchi, Ettore Appella, Mien-Chie Hung, Helen Piwnica-Worms
Journal: Cancer Cell (2008)
Elevated Depressive Symptoms, Antidepressant Use, and Diabetes in a Large Multiethnic National Sample of Postmenopausal Women
Authors: Yunsheng Ma, Raji Balasubramanian, Sherry L. Pagoto, Kristin L. Schneider, Annie L. Culver, Barbara Olendzki, Lesley Tinker, Simin Liu, Monika Safford, Deidre M. Sepavich, Milagros C. Rosal, Judith K. Ockene, Mercedes Carnethon, Martha Zorn, James R. Hébert
Journal: Diabetes Care (2011)

To examine elevated depressive symptoms and antidepressant use in relation to diabetes incidence in the Women's Health Initiative.A total of 161,808 postmenopausal women were followed for over an average of 7.6 years. Hazard ratios (HRs) estimating the effects of elevated depressive symptoms and antidepressant use on newly diagnosed incident diabetes were obtained using Cox proportional hazards models adjusted for known diabetes risk factors.Multivariable-adjusted HRs indicated an increased risk of incident diabetes with elevated baseline depressive symptoms (HR 1.13 [95% CI 1.07-1.20]) and antidepressant use (1.18 [1.10-1.28]). These associations persisted through year 3 data, in which respective adjusted HRs were 1.23 (1.09-1.39) and 1.31 (1.14-1.50).Postmenopausal women with elevated depressive symptoms who also use antidepressants have a greater risk of developing incident diabetes. In addition, longstanding elevated depressive symptoms and recent antidepressant medication use increase the risk of incident diabetes.
Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial
Authors: Mats Engström, Thomas Berg, Anna Stjernquist-Desatnik, Sara Axelsson, Anne Pitkäranta, Malou Hultcrantz, Mervi Kanerva, Per Hanner, Lars Jonsson
Journal: The Lancet Neurology (2008)
Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity
Authors: Eric E. Kelley, Jeff Baust, Gustavo Bonacci, Franca Golin-Bisello, Jason E. Devlin, Claudette M. St. Croix, Simon C. Watkins, Sonia Gor, Nadiezhda Cantu-Medellin, Eric R. Weidert, Jefferson C. Frisbee, Mark T. Gladwin, Hunter C. Champion, Bruce A. Freeman, Nicholas K.H. Khoo
Journal: Cardiovascular Research (2014)

AimsObesity is a risk factor for diabetes and cardiovascular diseases, with the incidence of these disorders becoming epidemic. Pathogenic responses to obesity have been ascribed to adipose tissue (AT) dysfunction that promotes bioactive mediator secretion from visceral AT and the initiation of pro-inflammatory events that induce oxidative stress and tissue dysfunction. Current understanding supports that suppressing pro-inflammatory and oxidative events promotes improved metabolic and cardiovascular function. In this regard, electrophilic nitro-fatty acids display pleiotropic anti-inflammatory signalling actions.
Impact of Two Supportive Care Interventions on Anxiety, Depression, Quality of Life, and Unmet Needs in Patients With Nonlocalized Breast and Colorectal Cancers
Authors: Afaf Girgis, Sibilah Breen, Fiona Stacey, Christophe Lecathelinais
Journal: Journal of Clinical Oncology (2009)

Purpose Patients with cancer experience considerable symptom burden, psychological morbidity, and unmet psychosocial needs. Research suggests that feedback of patient-reported outcomes to clinicians or caseworkers, alongside management strategies, may result in improved patient functioning. Two intervention models were developed to test this effect in a randomized, controlled trial against usual care (UC): a telephone caseworker (TCW) model and an oncologist/general practitioner (O/GP) model. Primary end points included anxiety, depression, physical/emotional functioning, and unmet supportive care needs. Patients and Methods Participants with nonlocalized breast or colorectal cancers were surveyed by computer-assisted telephone interview (CATI) at three time points: baseline, 3 months, and 6 months. Data collected from participant CATIs in the supportive care models were used to generate feedback to either each participant's designated TCW, or their nominated O/GPs. Data obtained from participants in the UC model were used only to assess the impact of supportive care models. In total, 356 participants consented to study participation, completed the baseline CATI, and were randomly assigned to the UC, TCW, or O/GP groups. Results No overall intervention effect was observed. Physical functioning was significantly improved at the third CATI for participants in the TCW model (P = .01), and there was a trend toward fewer participants with unmet needs (P = .07). TCW group participants also were more likely to have the following: identified issues of need discussed (P &lt; .0001); referrals made (P &lt; .0001); and strong agreement that the intervention improved communication with their health care team (P = .0005). Conclusion The TCW model holds some promise; however, additional work in at-risk populations is required before we recommend implementation.
MutPred Splice: machine learning-based prediction of exonic variants that disrupt splicing
Authors: Matthew Mort, Timothy Sterne-Weiler, Biao Li, Edward V Ball, David N Cooper, Predrag Radivojac, Jeremy R Sanford, Sean D Mooney
Journal: Genome biology (2014)

We have developed a novel machine-learning approach, MutPred Splice, for the identification of coding region substitutions that disrupt pre-mRNA splicing. Applying MutPred Splice to human disease-causing exonic mutations suggests that 16% of mutations causing inherited disease and 10 to 14% of somatic mutations in cancer may disrupt pre-mRNA splicing. For inherited disease, the main mechanism responsible for the splicing defect is splice site loss, whereas for cancer the predominant mechanism of splicing disruption is predicted to be exon skipping via loss of exonic splicing enhancers or gain of exonic splicing silencer elements. MutPred Splice is available at http://mutdb.org/mutpredsplice.
One-Year Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with Diabetic Macular Edema
Authors: Diana V. Do, Quan Dong Nguyen, David Boyer, Ursula Schmidt-Erfurth, David M. Brown, Robert Vitti, Alyson J. Berliner, Bo Gao, Oliver Zeitz, Rene Ruckert, Thomas Schmelter, Rupert Sandbrink, Jeff S. Heier
Journal: Ophthalmology (2012)
Serum leptin and adiponectin in obese and non-obese asthmatic school children: Relation to asthma control
Authors: Atqah Abdul Wahab, Muna Maarafiya, Ashraf Soliman, Noura Younes, Prem Chandra
Journal: European Respiratory Journal (2013)

Background:There is growing evidence of a positive correlation between asthma and obesity in children and adults. Leptin and adiponectin are produced by adipose tissue that regulates several metabolic and inflammatory functions.  Purpose: To measure serum leptin and adiponectin concentrations in obese asthmatic (OA) and non-obese asthmatic (NOA) children, and to investigate the association between their levels in relation to asthma control.  Methods: OA and NOA children, aged 7 to 14 years were enrolled in the study. The subjects were distributed into three groups according to their asthma control levels (well controlled, partial controlled and uncontrolled asthma). Body mass index (BMI) Z score, spirometry, IgE, serum leptin and adiponectin were measured.  Results: Serum leptin levels in 29 OA were significantly higher compared to 31 NOA children (25.8±11.1vs 8.7±11.1: (P  Conclusion: BMI Z score, leptin and adiponectin concentrations did not differ significantly among the asthma severity groups ruling out a significant effect of these variables on the severity of asthma control. A larger prospective study needs to be conducted for generalization and validity of the above findings.
Multidisciplinary management of lung cancer in a university teaching hospital in Algiers
Authors: Souad Souilah, F.Z. El Allia, A. Fissah, S. Taright, R. Amrane
Journal: European Respiratory Journal (2013)

The evaluation of decisions in the multidisciplinary meeting (MDM) is a useful tool for the analysis of professional practices. We report our experience of doing a retrospective analysis of new cases of lung cancer presented in MDM from 2006 to 2011 with comparison between MDM and decisions support real patient. 962 records submitted on first line, there were 794 cases of lung cancer (88% men) mostly NSCLC: 88.2% (33.9% adenocarcinoma, squamous 41.6%), advanced stage (stage III 30.4%, stage IV 57%). At the first presentation of the case histology was present in 98% of cases, the T and N defined in all patients, TNM was complete in 50.8% of cases. Average of three weeks elapsed between the first imaging and histological evidence, then a week before the proposed therapeutic MDM, the average time between MDM and the treatment was variable (1 week in case of chemotherapy, 3 weeks if surgery, 15 weeks in case of radiotherapy). The compliance rate for surgical decision was 80% (non-compliance was due to disruption of functional assessment preoperative) chemotherapy for 82% (non-compliance due to a deterioration of the general condition and the patient9s refusal) and the treatment with chemoradiotherapy 49%. 100% compliance decisions investigations, surveillance or symptomatic treatment. The overall compliance rate was 77.7%, the implementation of decisions taken was faced with several challenges such as availability of antimitotic treatment the difficulty of access to some care.
IFN-β Is a Highly Potent Inhibitor of Gastroenteropancreatic Neuroendocrine Tumor Cell Growth <i>In vitro</i>
Authors: Giovanni Vitale, Wouter W. de Herder, Peter M. van Koetsveld, Marlijn Waaijers, Wenda Schoordijk, Ed Croze, Annamaria Colao, Steven W.J. Lamberts, Leo J. Hofland
Journal: Cancer Research (2006)

IFN-alpha controls hormone secretion and symptoms in human gastroenteropancreatic neuroendocrine tumors (GEP-NET) but it rarely induces a measurable tumor size reduction. The effect of other type I IFNs, e.g., IFN-beta, has not been evaluated. We compared the antitumor effects of IFN-alpha and IFN-beta in BON cells, a functioning human GEP-NET cell line. As determined by quantitative reverse transcription-PCR analysis and immunocytochemistry, BON cells expressed the active type I IFN receptor mRNA and protein (IFNAR-1 and IFNAR-2c subunits). After 3 and 6 days of treatment, IFN-beta significantly inhibited BON cell growth in a time- and dose-dependent manner. IC50 and maximal inhibitory effect on day 6 were 8 IU/mL and 98%, respectively. In contrast, the effect of IFN-alpha resulted significantly in a less potent effect (IC50: 44 IU/mL, maximal inhibition: 26%). IFN-alpha induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-beta, apart from a more potent delay in S-G2-M phase transit of the cell cycle, also induced a strong stimulation of apoptosis, evaluated by flow cytometry (Annexin V and 7-AAD) and measurement of the DNA fragmentation. Besides, only IFN-beta severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment. In conclusion, IFN-beta is much more potent, compared with IFN-alpha, in its inhibitory effect on GEP-NET cell proliferation in vitro through the induction of apoptosis and cell cycle arrest. Further studies are required to establish whether IFN-beta has comparable potent tumor growth inhibitory effects in vivo.
Phase II Proof-of-Concept Study of Pazopanib Monotherapy in Treatment-Naive Patients With Stage I/II Resectable Non–Small-Cell Lung Cancer
Authors: Nasser Altorki, Maureen E. Lane, Thomas Bauer, Paul C. Lee, Michael J. Guarino, Harvey Pass, Enriqueta Felip, Nili Peylan-Ramu, Alfonso Gurpide, Frederic W. Grannis, John D. Mitchell, Sabrina Tachdjian, R. Suzanne Swann, Anne Huff, Debasish F. Roychowdhury, Anthony Reeves, Lone H. Ottesen, David F. Yankelevitz
Journal: Journal of Clinical Oncology (2010)

Purpose Patients with early-stage, resectable, non–small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC. Patients and Methods Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients. Results Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction ≥ 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment. Conclusion Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.
Comparison of treatment effects between animal experiments and clinical trials: systematic review
Authors: Pablo Perel, Ian Roberts, Emily Sena, Philipa Wheble, Catherine Briscoe, Peter Sandercock, Malcolm Macleod, Luciano E Mignini, Pradeep Jayaram, Khalid S Khan
Journal: BMJ (2006)

Objective To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. Data sources Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. Study selection Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome. Results Corticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (−1.4% to 4.7%). Conclusions Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.
Worsening Trends in the Management and Treatment of Back Pain
Authors: John N. Mafi, Ellen P. McCarthy, Roger B. Davis, Bruce E. Landon
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Back pain treatment is costly and frequently includes overuse of treatments that are unsupported by clinical guidelines. Few studies have evaluated recent national trends in guideline adherence of spine-related care. <h3>Objective</h3> To characterize the treatment of back pain from January 1, 1999, through December 26, 2010. <h3>Design, Setting, and Patients</h3> Using nationally representative data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, we studied outpatient visits with a chief symptom and/or primary diagnosis of back or neck pain, as well as those with secondary symptoms and diagnoses of back or neck pain. We excluded visits with concomitant “red flags,” including fever, neurologic symptoms, or cancer. Results were analyzed using logistic regression adjusted for patient and health care professional characteristics and weighted to reflect national estimates. We also present adjusted results stratified by symptom duration and whether the health care professional was the primary care physician (PCP). <h3>Main Outcomes and Measures</h3> We assessed imaging, narcotics, and referrals to physicians (guideline discordant indicators). In addition, we evaluated use of nonsteroidal anti-inflammatory drugs or acetaminophen and referrals to physical therapy (guideline concordant indicators). <h3>Results</h3> We identified 23 918 visits for spine problems, representing an estimated 440 million visits. Approximately 58% of patients were female. Mean age increased from 49 to 53 years (<i>P</i> &lt; .001) during the study period. Nonsteroidal anti-inflammatory drug or acetaminophen use per visit decreased from 36.9% in 1999-2000 to 24.5% in 2009-2010 (unadjusted<i>P</i> &lt; .001). In contrast, narcotic use increased from 19.3% to 29.1% (<i>P</i> &lt; .001). Although physical therapy referrals remained unchanged at approximately 20%, physician referrals increased from 6.8% to 14.0% (<i>P</i> &lt; .001). The number of radiographs remained stable at approximately 17%, whereas the number of computed tomograms or magnetic resonance images increased from 7.2% to 11.3% during the study period (<i>P</i> &lt; .001). These trends were similar after stratifying by short-term vs long-term presentations, visits to PCPs vs non-PCPs, and adjustment for age, sex, race/ethnicity, PCP status, symptom duration, region, and metropolitan location. <h3>Conclusions and Relevance</h3> Despite numerous published clinical guidelines, management of back pain has relied increasingly on guideline discordant care. Improvements in the management of spine-related disease represent an area of potential cost savings for the health care system with the potential for improving the quality of care.
N-Cadherin Expression and Epithelial-Mesenchymal Transition in Pancreatic Carcinoma
Authors: Sanae Nakajima, Ryuichiro Doi, Eiji Toyoda, Shoichiro Tsuji, Michihiko Wada, Masayuki Koizumi, Sidhartha S. Tulachan, Daisuke Ito, Kazuhiro Kami, Tomohiko Mori, Yoshiya Kawaguchi, Koji Fujimoto, Ryo Hosotani, Masayuki Imamura
Journal: Clinical Cancer Research (2004)

Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors.We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)beta, and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines.N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change.This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.
Prehospital Termination of Resuscitation in Cases of Refractory Out-of-Hospital Cardiac Arrest
Authors: Comilla Sasson
Journal: JAMA (2008)

Identifying patients in the out-of-hospital setting who have no realistic hope of surviving an out-of-hospital cardiac arrest could enhance utilization of scarce health care resources.To validate 2 out-of-hospital termination-of-resuscitation rules developed by the Ontario Prehospital Life Support (OPALS) study group, one for use by responders providing basic life support (BLS) and the other for those providing advanced life support (ALS).Retrospective cohort study using surveillance data prospectively submitted by emergency medical systems and hospitals in 8 US cities to the Cardiac Arrest Registry to Enhance Survival (CARES) between October 1, 2005, and April 30, 2008. Case patients were 7235 adults with out-of-hospital cardiac arrest; of these, 5505 met inclusion criteria.Specificity and positive predictive value of each termination-of-resuscitation rule for identifying patients who likely will not survive to hospital discharge.The overall rate of survival to hospital discharge was 7.1% (n = 392). Of 2592 patients (47.1%) who met BLS criteria for termination of resuscitation efforts, only 5 (0.2%) patients survived to hospital discharge. Of 1192 patients (21.7%) who met ALS criteria, none survived to hospital discharge. The BLS rule had a specificity of 0.987 (95% confidence interval [CI], 0.970-0.996) and a positive predictive value of 0.998 (95% CI, 0.996-0.999) for predicting lack of survival. The ALS rule had a specificity of 1.000 (95% CI, 0.991-1.000) and positive predictive value of 1.000 (95% CI, 0.997-1.000) for predicting lack of survival.In this validation study, the BLS and ALS termination-of-resuscitation rules performed well in identifying patients with out-of-hospital cardiac arrest who have little or no chance of survival.