tbuckley/cabot-search huggingface dataset:
Effects of Cognitive Bias Modification Training on Neural Alcohol Cue Reactivity in Alcohol Dependence
Authors: Corinde E. Wiers, Christine Stelzel, Thomas E. Gladwin, Soyoung Q. Park, Steffen Pawelczack, Christiane K. Gawron, Heiner Stuke, Andreas Heinz, Reinout W. Wiers, Mike Rinck, Johannes Lindenmeyer, Henrik Walter, Felix Bermpohl
Journal: American Journal of Psychiatry (2014)

Objective: In alcohol-dependent patients, alcohol cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on cue reactivity in alcohol-dependent patients. Method: In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol cues and 10% of soft drink cues, whereas this ratio was 50/50 in the sham training. Alcohol cue reactivity was measured with functional MRI before and after training. Results: Before training, alcohol cue-evoked activation was observed in the amygdala bilaterally, as well as in the right nucleus accumbens, although here it fell short of significance. Activation in the amygdala correlated with craving and arousal ratings of alcohol stimuli; correlations in the nucleus accumbens again fell short of significance. After training, the bias modification group showed greater reductions in cue-evoked activation in the amygdala bilaterally and in behavioral arousal ratings of alcohol pictures, compared with the sham training group. Decreases in right amygdala activity correlated with decreases in craving in the bias modification but not the sham training group. Conclusions: These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.
Microlavage: a technique for determining the volume of epithelial lining fluid.
Authors: D R Baldwin, R Wise, J M Andrews, D Honeybourne
Journal: Thorax (1991)

A new technique ("microlavage") was used to determine the volume of epithelial lining fluid recovered by bronchoalveolar lavage. A standard bronchial brush tube is used to lavage a peripheral lung subsegment rapidly with 20 ml of normal saline and the concentrations of urea and total protein are measured in the aspirated fluid. Using a very short dwell time for fluid (less than 20 seconds), this technique allows the urea dilution method to be used to quantify the epithelial lining fluid protein concentration, which is then used as an endogenous marker of the epithelial lining fluid in conventional bronchoalveolar lavage fluid. The reproducibility of the calculation of the concentration of the lining fluid protein was assessed in 10 patients by performing the method in three separate lung subsegments. The mean coefficient of variation of the urea to protein ratio was 9.0%. A comparison of microlavage and conventional lavage was made in a further 28 patients. The differential cell counts were similar by the two methods, suggesting that similar epithelial lining fluid was sampled. The application of the microlavage technique to the calculation of epithelial lining fluid volume gave a lower value than the urea dilution method in association with conventional lavage. Microlavage should provide more accurate quantification of epithelial lining fluid volume and could be used in conjunction with conventional lavage, which is still required for an adequate harvest of alveolar cells.
Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy
Authors: Dawn L. Hershman, Joseph M. Unger, Katherine D. Crew, Lori M. Minasian, Danielle Awad, Carol M. Moinpour, Lisa Hansen, Danika L. Lew, Heather Greenlee, Louis Fehrenbacher, James L. Wade, Siu-Fun Wong, Gabriel N. Hortobagyi, Frank L. Meyskens, Kathy S. Albain
Journal: Journal of Clinical Oncology (2013)

Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN.A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] -Fatigue), and NTX grade.A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo.There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.
Comparison of UV-induced skin changes in sun-exposed vs. sun-protected skin- preliminary evaluation by reflectance confocal microscopy
Authors: M. Ulrich, C. Rüter, S. Astner, W. Sterry, B. Lange-Asschenfeldt, E. Stockfleth, J. Röwert-Huber
Journal: British Journal of Dermatology (2009)

UV radiation (UVR) represents the main risk factor for skin cancer. Sunscreens are commonly used to prevent acute and chronic effects of UVR. The efficacy of sunscreens is currently determined by measurement of minimal erythema dose. Reflectance confocal microscopy represents a non-invasive imaging technique that allows the in- vivo characterization of the skin at near histological resolution.The aim of this study was to compare standardized clinical and histological features of UV-exposure with morphological changes detected by RCM.RCM allowed the detection of morphological changes induced by UV including spongiosis, sunburn cells, micro-vesicles and blood vessel dilatation. The appearance of sunburn cells and micro-vesicles was depending on the dose of UV-B and on the individual susceptibility of the study participants.RCM seems to be beneficial for the non-invasive evaluation of dynamic changes following acute UV exposure. Similar to histopathology RCM allows the characterization of sunburn cells and micro-vesicle formation as a sign for acute photo damage. RCM may therefore be used for classification of sunburn reaction and to test the efficacy of sunscreens on a cellular level.
Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
Authors: Louisa CE Windus, Tristan T Glover, Vicky M Avery
Journal: Molecular Cancer (2013)

Abstract Background The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediating tumour-stromal interactions. Methods Utilising 3D in vitro assays we evaluated and compared 1. Monocultures of prostate metastatic PC3, bone stromal derived HS5 and prostate epithelial RWPE-1 cells and 2. Tumour-stromal co-cultures (PC3 + HS5) to ascertain changes in cellular phenotype, function and expression of metastatic markers. Results In comparison to 3D monocultures of PC3 or HS5 cells, when cultured together, these cells displayed up-regulated invasive and proliferative qualities, along with altered expression of epithelial-to-mesenchymal and chemokine protein constituents implicated in metastatic dissemination. When co-cultured, HS5 cells were found to re-express N-Cadherin and chemokine receptor CXCR7. Alterations in N-Cadherin expression were found to be mediated by soluble factors secreted by PC3 tumour cells, while chemokine receptor re-expression was dependent on direct cell-cell interactions. We have also shown that integrins beta 1 and alpha 6 play an integral role in maintaining cell homeostasis and mediating expression of E-Cadherin, N-Cadherin and vimentin, in addition to chemokine receptor CXCR7. Conclusions Collectively our results suggest that both PC3 and HS5 cells provide a “protective” and reciprocal milieu that promotes tumour growth. As such 3D co-cultures may serve as a more complex and valid biological model in the drug discovery pipeline.
P05 Combination of serum biomarkers for the diagnosis of hepatocellular carcinoma
Authors: P. Johnson, M. Teng, S. Pirrie, D. Palmer, S. Berhane, D. Stocken
Journal: Gut (2011)

<h3>Introduction</h3> The most commonly used serum biomarker for the diagnosis of hepatocellular carcinoma (HCC) is α fetoprotein (AFP). However, AFP is also modestly raised in patients with chronic liver disease, particularly in those who are at a higher risk of developing HCC. A number of other circulating markers such as des-γ carboxy prothrombin (DCP) and the Lens culinaris agglutinin-reactive fraction of α-fetoprotein (L3) have been shown to have diagnostic discrimination which may, in certain situations, be superior to AFP. <h3>Aim</h3> We therefore aimed to build a model that combined these biomarkers with baseline liver function tests, in order to identify those factors which predict HCC and might improve diagnostic efficacy of AFP alone. <h3>Method</h3> A prospective study was specifically designed to assess the diagnostic efficacy of biomarkers. 461 serum samples were collected between 2007 and 2011: 252 were controls samples from patients with chronic liver disease with no evidence of HCC within 6 months of the sample; 59 were from patients with early HCC which was potentially curable and 150 were from patients with late HCC. AFP, AFP-L3 and DCP were measured in serum samples using a new micro total analysis system (Wako Chemicals GmbH, Neuss, Germany). Patients were classified into two groups (HCC, control) for the primary analysis. Independent predictors of HCC were identified from multivariable logistic regression analyses. The impact of AFP, DCP and L3 are reported based on the area under the receiver operator curve (AUC). <h3>Results</h3> Univariate analysis showed AFP alone to have OR=2.96 (2.34 to 3.73 95% CI), AUC =0.8723, p&lt;0.001. A multivariable model selected age, sex, AST, ALP and INR as independent predictors of HCC with an overall model AUC =0.8857. Including AFP, DCP and L3 to this model increased the AUC to 0.9489, 0.9290, 0.9254 respectively. The final model included age, sex, AFP, DCP and INR gave an AUC of 0.9661 (95% CI 0.95 to 0.98) for all patients and 0.944 (95% CI 0.914 to 0.974) for early HCC patients. <h3>Conclusion</h3> A combination of serum markers may produce a clinically useful diagnostic test for HCC compared to AFP alone. Further validation of our model is underway on an independent dataset. These findings suggest that our model may enhance or replace the current screening approach for patients with liver cirrhosis, particularly since it appears to have efficacy even in patients with early, potentially curable, disease.
Rosuvastatin in Diabetic Hemodialysis Patients
Authors: Hallvard Holdaas, Ingar Holme, Roland E. Schmieder, Alan G. Jardine, Faiez Zannad, Gudrun E. Norby, Bengt C. Fellström
Journal: Journal of the American Society of Nephrology (2011)

A randomized, placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint, but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk. Because the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial included patients with and without diabetes, we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis. Among the 731 participants with diabetes, traditional risk factors such as LDL-C, smoking, and BP did not associate with cardiac events (cardiac death and nonfatal myocardial infarction). At baseline, only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events. Assignment to rosuvastatin associated with a nonsignificant 16.2% reduction in risk for the AURORA trial's composite primary endpoint of cardiac death, nonfatal MI, or fatal or nonfatal stroke (HR 0.84; 95% CI 0.65 to 1.07). There was no difference in overall stroke, but the rosuvastatin group had more hemorrhagic strokes than the placebo group (12 versus two strokes, respectively; HR, 5.21; 95% CI 1.17 to 23.27). Rosuvastatin treatment significantly reduced the rates of cardiac events by 32% among patients with diabetes (HR 0.68; 95% CI 0.51 to 0.90). In conclusion, among hemodialysis patients with diabetes mellitus, rosuvastatin might reduce the risk of fatal and nonfatal cardiac events.
Carcinoma Erysipeloides From Ovarian Clear-Cell Carcinoma
Authors: Hsing-Chuan Lee, Chia-Yu Chu, Cheng-Hsiang Hsiao
Journal: Journal of Clinical Oncology (2007)

8][9] In conclusion, ovarian cancer rarely metastasizes to the skin, and if it does, it usually manifests as abdominal cutaneous nodules.In rare situations, it may present as carcinoma erysipeloides mimicking erysipelas or cellulitis.Physicians should keep in mind the possibility of carcinoma erysipeloides when there is erysipelas or cellulitis-like skin lesions in the lower abdomen or thighs in a patient with ovarian carcinoma.
Transmission of Lymphocytic Choriomeningitis Virus by Organ Transplantation
Authors: Staci A. Fischer, Mary Beth Graham, Matthew J. Kuehnert, Camille N. Kotton, Arjun Srinivasan, Francisco M. Marty, James A. Comer, Jeannette Guarner, Christopher D. Paddock, Dawn L. DeMeo, Wun-Ju Shieh, Bobbie R. Erickson, Utpala Bandy, Alfred DeMaria, Jeffrey P. Davis, Francis L. Delmonico, Boris Pavlin, Anna Likos, Martin J. Vincent, Tara K. Sealy, Cynthia S. Goldsmith, Daniel B. Jernigan, Pierre E. Rollin, Michelle M. Packard, Mitesh Patel, Courtney Rowland, Rita F. Helfand, Stuart T. Nichol, Jay A. Fishman, Thomas Ksiazek, Sherif R. Zaki
Journal: New England Journal of Medicine (2006)

In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized.
The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case–control study
Authors: W G Dixon, A Kezouh, S Bernatsky, S Suissa
Journal: Annals of the Rheumatic Diseases (2011)

Background Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. Methods A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case–control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. Results For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (&lt;5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including &lt;5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). Conclusion Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year.
Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea
Authors: M.M.T. Fawzi, S.O. Tawfik, A.M. Eissa, M.H.M. El-Komy, M.R.E. Abdel-Halim, O.G. Shaker
Journal: British Journal of Dermatology (2008)

Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders.To evaluate the role of IGF-I in the pathogenesis of morphoea.The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique.IGF-I in lesional skin was significantly higher than in non-lesional and control skin (P = 0.001 and P = 0.021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum (P < 0.001). A direct significant correlation existed between lesional and non-lesional skin level (r = 0.618, P = 0.014), and between lesional skin level and Rodnan score (r = 0.538, P = 0.039).Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea.
Phase I Study of Decitabine in Combination with Vorinostat in Patients with Advanced Solid Tumors and Non-Hodgkin's Lymphomas
Authors: Anastasios Stathis, Sebastien J. Hotte, Eric X. Chen, Holger W. Hirte, Amit M. Oza, Patricia Moretto, Sheila Webster, Anne Laughlin, Lee-Anne Stayner, Shauna McGill, Lisa Wang, Wen-jiang Zhang, Igor Espinoza-Delgado, Julianne L. Holleran, Merrill J. Egorin, Lillian L. Siu
Journal: Clinical Cancer Research (2011)

PURPOSE: This phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary efficacy of the combination of decitabine with vorinostat. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphomas were eligible. Sequential and concurrent schedules were studied. RESULTS: Forty-three patients were studied in 9 different dose levels (6 sequential and 3 concurrent). The maximum tolerated dose (MTD) on the sequential schedule was decitabine 10 mg/m(2)/day on days 1-5 and vorinostat 200 mg three times a day on days 6-12. The MTD on the concurrent schedule was decitabine 10 mg/m(2)/day on days 1-5 with vorinostat 200 mg twice a day on days 3-9. However, the sequential schedule of decitabine 10 mg/m(2)/day on days 1-5 and vorinostat 200 mg twice a day on days 6-12 was more deliverable than both MTDs with fewer delays on repeated dosing and it represents the recommended phase II (RP2D) dose of this combination. Dose-limiting toxicities during the first cycle consisted of myelosuppression, constitutional and gastrointestinal symptoms and occurred in 12/42 (29%) patients evaluable for toxicity. The most common ≥ grade 3 adverse events were neutropenia (49% of patients), thrombocytopenia (16%), fatigue (16%), lymphopenia (14%), and febrile neutropenia (7%). Disease stabilization for ≥ 4 cycles was observed in 11/38 (29%) evaluable patients. CONCLUSION: The combination of decitabine with vorinostat is tolerable on both concurrent schedules in previously treated patients with advanced solid tumors or non-Hodgkin's lymphomas. The sequential schedule was easier to deliver. The combination showed activity with prolonged disease stabilization in different tumor types.
Vinflunine: A New Microtubule Inhibitor Agent
Authors: Jaafar Bennouna, Jean-Pierre Delord, Mario Campone, Laurent Nguyen
Journal: Clinical Cancer Research (2008)

Abstract Vinflunine (Javlor) is the first fluorinated microtubule inhibitor belonging to the Vinca alkaloids family. Vinflunine is obtained by semisynthesis using superacidic chemistry to selectively introduce two fluorine atoms at the 20′ position of the catharanthine moiety. This compound has been selected for clinical development on the basis of encouraging preclinical activity that warrants study in patients with a wide spectrum of solid tumors. Clinically significant activity has been seen in phase II studies, mainly in the treatment of transitional cell carcinoma of the urothelial tract, non–small cell lung cancer, and carcinoma of the breast. Vinflunine is currently in phase III trial assessment in patients with (second line) transitional cell carcinoma of the urothelium and first-line advanced breast cancer. The efficacy of vinflunine in patients with advanced non–small cell lung cancer previously treated with a platinum-containing regimen was confirmed by a large phase III trial.