tbuckley/cabot-search huggingface dataset:
TCT-466 Paclitaxel-coated Balloon Versus Drug-eluting Stent for the Treatment of In-stent Restenosis in Patients with Renal Failure on Hemodialysis
Authors: Yusuke Hyodo, Yasushi Fuku, Tsuyoshi Goto, Seiji Habara, Daiji Hasegawa, Kazushige Kadota, Kazuaki Mitsudo, Suguru Otsuru, Yoshikazu Shigemoto, Takeshi Tada, Hiroyuki Tanaka
Journal: Journal of the American College of Cardiology (2013)
Awareness and Use of California's Paid Family Leave Insurance Among Parents of Chronically Ill Children
Authors: Mark A. Schuster
Journal: JAMA (2008)

In 2004, California's Paid Family Leave Insurance Program (PFLI) became the first state program to provide paid leave to care for an ill family member.To assess awareness and use of the program by employed parents of children with special health care needs, a population likely to need leave.Telephone interviews with successive cohorts of employed parents before (November 21, 2003-January 31, 2004; n = 754) and after (November 18, 2005-January 31, 2006; n = 766) PFLI began, randomly sampled from 2 children's hospitals, one in California (with PFLI) and the other in Illinois (without PFLI). Response rates were 82% before and 81% after (California), and 80% before and 74% after (Illinois).Taking leave, length of leave, unmet need for leave, and awareness and use of PFLI.Similar percentages of parents at the California site reported taking at least 1 day of leave to care for their ill child before (295 [81%]) and after (327 [79%]) PFLI, taking at least 4 weeks before (64 [21%]) and after (74 [19%]) PFLI, and at least once in the past year not missing work despite believing their child's illness necessitated it before (152 [41%]) and after (156 [41%]) PFLI. Relative to Illinois, parents at the California site reported no change from before to after PFLI in taking at least 1 day of leave (difference of differences, -3%; 95% confidence interval [CI], -13% to 7%); taking at least 4 weeks of leave (1%; 95% CI, -9% to 10%); or not missing work, despite believing their child's illness necessitated it (-1%; 95% CI, -13% to 10%). Only 77 parents (18%) had heard of PFLI approximately 18 months after the program began, and only 20 (5%) had used it. Even among parents without other access to paid leave, awareness and use of PFLI were minimal.Parents of children with special health care needs receiving care at a California hospital were generally unaware of PFLI and rarely used it. Among parents of children with special health care needs, taking leave in California did not increase after PFLI implementation compared with Illinois.
BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance
Authors: Hilmar Quentmeier, Sonja Eberth, Julia Romani, Margarete Zaborski, Hans G Drexler
Journal: Journal of Hematology & Oncology (2011)

The BCR-ABL1 translocation occurs in chronic myeloid leukemia (CML) and in 25% of cases with acute lymphoblastic leukemia (ALL). The advent of tyrosine kinase inhibitors (TKI) has fundamentally changed the treatment of CML. However, TKI are not equally effective for treating ALL. Furthermore, de novo or secondary TKI-resistance is a significant problem in CML. We screened a panel of BCR-ABL1 positive ALL and CML cell lines to find models for imatinib-resistance. Five of 19 BCR-ABL1 positive cell lines were resistant to imatinib-induced apoptosis (KCL-22, MHH-TALL1, NALM-1, SD-1, SUP-B15). None of the resistant cell lines carried mutations in the kinase domain of BCR-ABL1 and all showed resistance to second generation TKI, nilotinib or dasatinib. STAT5, ERK1/2 and the ribosomal S6 protein (RPS6) are BCR-ABL1 downstream effectors, and all three proteins are dephosphorylated by imatinib in sensitive cell lines. TKI-resistant phosphorylation of RPS6, but responsiveness as regards JAK/STAT5 and ERK1/2 signalling were characteristic for resistant cell lines. PI3K pathway inhibitors effected dephosphorylation of RPS6 in imatinib-resistant cell lines suggesting that an oncogene other than BCR-ABL1 might be responsible for activation of the PI3K/AKT1/mTOR pathway, which would explain the TKI resistance of these cells. We show that the TKI-resistant cell line KCL-22 carries a PI3Kα E545G mutation, a site critical for the constitutive activation of the PI3K/AKT1 pathway. Apoptosis in TKI-resistant cells could be induced by inhibition of AKT1, but not of mTOR. We introduce five Philadelphia-chromosome positive cell lines as TKI-resistance models. None of these cell lines carries mutations in the kinase domain of BCR-ABL1 or other molecular aberrations previously indicted in the context of imatinib-resistance. These cell lines are unique as they dephosphorylate ERK1/2 and STAT5 after treatment with imatinib, while PI3K/AKT1/mTOR activity remains unaffected. Inhibition of AKT1 leads to apoptosis in the imatinib-resistant cell lines. In conclusion, Ph+ cell lines show a form of imatinib-resistance attributable to constitutive activation of the PI3K/AKT1 pathway. Mutations in PIK3CA, as observed in cell line KCL-22, or PI3K activating oncogenes may undelie TKI-resistance in these cell lines.
Psychiatric Aspects of Impulsivity
Authors: F. Gerard Moeller, Ernest S. Barratt, Donald M. Dougherty, Joy M. Schmitz, Alan C. Swann
Journal: American Journal of Psychiatry (2001)

The authors discuss the relationship of impulsivity to psychiatric disorders and present selected hypotheses regarding the reasons for these relationships.Previous research has shown significantly higher levels of impulsivity among patients with conduct disorder, personality disorders, substance use disorders, and bipolar disorder, compared to other psychiatric patients or healthy comparison subjects. A literature review of the theoretical bases of the relationship between these disorders and impulsivity is presented. Measurements of impulsivity and treatment options are discussed in relation to the physiology of impulsivity and the disorders in which it is a prominent feature.Impulsivity, as defined on the basis of a biopsychosocial approach, is a key feature of several psychiatric disorders. Behavioral and pharmacological interventions that are effective for treating impulsivity should be incorporated into treatment plans for these disorders.The high comorbidity of impulsivity and selected psychiatric disorders, including personality disorders, substance use disorders, and bipolar disorder, is in a large part related to the association between impulsivity and the biological substrates of these disorders. Before treatment studies on impulsivity can move forward, measures of impulsivity that capture the core aspects of this behavior need to be refined and tested on the basis of an ideologically neutral model of impulsivity.
‘Insights in the relationship of joint space narrowing versus erosive joint damage and physical functioning of patients with RA’
Authors: R Koevoets, L Dirven, N B Klarenbeek, M V van Krugten, H K Ronday, D M F M van der Heijde, T W J Huizinga, P S J M Kerstens, W F Lems, C F Allaart
Journal: Annals of the Rheumatic Diseases (2012)

Objective To evaluate the contribution of joint space narrowing (JSN) and erosions in general and in four different joint groups in relation to physical disability in rheumatoid arthritis (RA). Methods 5-year follow-up data from the Behandel Strategieën (BeSt) trial were used, where 508 patients with recent onset RA were treated aiming at a disease activity score ≤2.4. Joint damage was assessed annually and scored according to the Sharp-van der Heijde method. Physical disability was measured 3-monthly with the Health Assessment Questionnaire (HAQ). Generalised Estimating Equations analyses were performed to assess the relationship between the HAQ and JSN scores and erosions scores, separately and in joint groups. Results Overall, damage scores were low, and neither total JSN nor erosions showed a significant effect on HAQ (β=0.001 95% CI −0.003 to 0.004 and β=0.002 95% CI −0.001 to 0.006, respectively). Of the total damage scores per joint group, damage in the wrist shows a trend for association with physical disability displaying the largest effect size (β=0.005 95% CI 0.000 to 0.011). Also in the analysis with erosions per joint group, the wrist was most strongly related with physical functioning (β=0.016 95% CI 0.003 to 0.029); in the analysis with JSN per joint group no joint group was significantly related to the HAQ. Analysis of all erosion and narrowing scores per joint group in one model reveals only erosions in the wrist to be independently associated with impaired physical functioning (β=0.017 95% CI 0.003 to 0.030). Conclusions Joint damage in the wrist, erosions more than JSN, is associated with impaired physical functioning even in patients with early RA with limited overall damage after 5 years tightly controlled treatment.
Pulmonary neuronal M2 muscarinic receptor function in asthma and animal models of hyperreactivity
Authors: R W Costello, D B Jacoby, A D Fryer
Journal: Thorax (1998)

In the lungs neuronal M2 muscarinic receptors limit acetylcholine release from postganglionic cholinergic nerves. These inhibitory M2 receptors are dysfunctional in antigen challenged guinea pigs and in humans with asthma which leads to an increase in vagally mediated hyperreactivity. In vitro, eosinophil products act as allosteric antagonists at neuronal M2 muscarinic receptors. In vivo, displacing or neutralising MBP preserves neuronal M2 muscarinic receptor function and prevents hyperreactivity. Thus, there is good evidence from animal studies that after antigen challenge pulmonary M2 muscarinic receptors become dysfunctional because MBP inhibits their function. Loss of function of pulmonary neuronal M2 muscarinic receptors has also been reported in patients with asthma, although the clinical significance of this dysfunction and the mechanisms underlying it are not yet established.
150 minutes of vigorous physical activity per week predicts survival and successful ageing: a population-based 11-year longitudinal study of 12 201 older Australian men
Authors: Osvaldo P Almeida, Karim M Khan, Graeme J Hankey, Bu B Yeap, Jonathan Golledge, Leon Flicker
Journal: British Journal of Sports Medicine (2013)

Physical activity has been associated with improved survival, but it is unclear whether this increase in longevity is accompanied by preserved mental and physical functioning, also known as healthy ageing. We designed this study to determine whether physical activity is associated with healthy ageing in later life.We recruited a community-representative sample of 12 201 men aged 65-83 years and followed them for 10-13 years. We assessed physical activity at the beginning and the end of the follow-up period. Participants who reported 150 min or more of vigorous physical activity per week were considered physically active. We monitored survival during the follow-up period and, at study exit, assessed the mood, cognition and functional status of survivors. Healthy ageing was defined as being alive at the end of follow-up and having a Patient Health Questionnaire score <10, Telephone Interview for Cognitive Status score >27, and no major difficulty in any instrumental or basic activity of daily living. Cox regression and general linear models were used to estimate HR of death and risk ratio (RR) of healthy ageing. Analyses were adjusted for age, education, marital status, smoking, body mass index and history of hypertension, diabetes, coronary heart disease and stroke.Two thousand and fifty-eight (16.9%) participants were physically active at study entry. Active men had lower HR of death over 10-13 years than physically inactive men (HR=0.74, 95% CI=0.68 to 0.81). Among survivors, completion of the follow-up assessment was higher in the physically active than inactive group (risk ratio, RR=1.18, 95% CI=1.08 to 1.30). Physically active men had greater chance of fulfilling criteria for healthy ageing than inactive men (RR=1.35, 95% CI=1.19 to 1.53). Men who were physically active at the baseline and follow-up assessments had the highest chance of healthy ageing compared with inactive men (RR=1.59, 95% CI=1.36 to 1.86).Sustained physical activity is associated with improved survival and healthy ageing in older men. Vigorous physical activity seems to promote healthy ageing and should be encouraged when safe and feasible.
Genes expressed in blood link osteoarthritis with apoptotic pathways
Authors: Yolande F M Ramos, Steffan D Bos, Nico Lakenberg, Stefan Böhringer, Wouter J den Hollander, Margreet Kloppenburg, P Eline Slagboom, Ingrid Meulenbelt
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To identify novel gene expression networks in blood of osteoarthritis patients compared to controls. <h3>Methods</h3> A comprehensive exploration of gene expression in peripheral blood was performed by microarray analysis for a subset of osteoarthritis patients from the Genetics osteoARthritis and Progression (GARP) study in comparison with sex and age-matched healthy controls. To identify pathways, we performed gene enrichment analyses (database for annotation, visualisation and integrated discovery and search tool for the retrieval of interacting genes). Quantitative PCR analysis in overlapping and in additional osteoarthritis samples was performed for prioritised genes to validate and replicate findings. Classification of cases and controls was explored by applying statistical models. <h3>Results</h3> 741 probes representing 694 unique genes were differentially expressed between cases and controls, including 86 genes expressed with at least a 1.5-fold difference. <i>ATF4</i>, <i>GPR18</i> and <i>H3F3B</i> were among the top genes identified (p&lt;4.5 × 10<sup>−8</sup>). We found that in the blood of osteoarthritis patients the apoptosis pathway, including the well-known gene <i>CASP3</i>, was significantly enriched among the differentially expressed genes. Our findings were validated in independent samples and when using a small subset of the validated genes, we could accurately distinguish patients from controls (area under the curve 98%). <h3>Conclusions</h3> In the current study, we have identified specific gene expression networks, in the easily accessible tissue blood, which associated consistently with osteoarthritis among GARP study cases. Our data further hint at the relevance of apoptosis as an aetiological factor in osteoarthritis onset, thereby qualifying expression profiling of blood as a useful tool to understand the underlying molecular mechanisms of osteoarthritis.
Increased arachidonic acid composition of phospholipids in colonic mucosa from patients with active ulcerative colitis.
Authors: T Nishida, H Miwa, A Shigematsu, M Yamamoto, M Iida, M Fujishima
Journal: Gut (1987)

The long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12.5 +/- 1.4 mol % (mean +/- 2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6.8 +/- 1.2 mol % in the intact mucosa from healthy controls (p less than 0.001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p less than 0.001 and p less than 0.02, respectively), while docosahexaenoic acid was increased (p less than 0.05). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p less than 0.001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r = 0.89, p less than 0.005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.
Pharmacology of Cardiac and Vascular Remodeling
Authors: H A Struijker-Boudier, J F Smits, J G De Mey
Journal: The Annual Review of Pharmacology and Toxicology (1995)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Synaptojanin Is Recruited by Endophilin to Promote Synaptic Vesicle Uncoating
Authors: Patrik Verstreken, Tong-Wey Koh, Karen L. Schulze, R.Grace Zhai, P.Robin Hiesinger, Yi Zhou, Sunil Q. Mehta, Yu Cao, Jack Roos, Hugo J. Bellen
Journal: Neuron (2003)
Di(2-ethylhexyl) Phthalate Metabolites May Alter Thyroid Hormone Levels in Men
Authors: John D. Meeker, Antonia M. Calafat, Russ Hauser
Journal: Environmental Health Perspectives (2007)

Phthalates are used extensively in many personal-care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. A limited number of animal studies suggest that exposure to phthalates may be associated with altered thyroid function, but human data are lacking.Concurrent samples of urine and blood were collected from 408 men. We measured urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites, along with serum levels of free thyroxine (T(4)), total triiodothyronine (T(3)), and thyroid-stimulating hormone (TSH). Oxidative metabolites of DEHP were measured in urine from only 208 of the men.We found an inverse association between MEHP urinary concentrations and free T(4) and T(3) serum levels, although the relationships did not appear to be linear when MEHP concentrations were categorized by quintiles. There was evidence of a plateau at the fourth quintile, which was associated with a 0.11 ng/dL decrease in free T(4) [95% confidence interval (CI), -0.18 to -0.03] and a 0.05 ng/mL decrease in T(3) (95% CI, -0.10 to 0.01) compared with the first (lowest) MEHP quintile. The inverse relationship between MEHP and free T(4) remained when we adjusted for oxidative metabolite concentrations; this simultaneously demonstrated a suggestive positive association with free T(4).Urinary MEHP concentrations may be associated with altered free T(4) and/or total T(3) levels in adult men, but additional study is needed to confirm the observed findings. Future studies must also consider oxidative DEHP metabolites relative to MEHP as a potential marker of metabolic susceptibility to DEHP exposure.
Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial
Authors: Robert Haddad, Anne O'Neill, Guilherme Rabinowits, Roy Tishler, Fadlo Khuri, Douglas Adkins, Joseph Clark, Nicholas Sarlis, Jochen Lorch, Jonathan J Beitler, Sewanti Limaye, Sarah Riley, Marshall Posner
Journal: The Lancet Oncology (2013)
Subepidermal blistering disease with 3 distinct autoantibodies: Anti-BP230, anti-laminin gamma-1, and anti-laminin-332
Authors: Kazuhiro Kikuchi, Ken Natsuga, Satoru Shinkuma, Wataru Nishie, Satoshi Kajita, Hidetsugu Sato, Hiroshi Shimizu
Journal: Journal of the American Academy of Dermatology (2011)
Phase I Trial of Bortezomib and Carboplatin in Recurrent Ovarian or Primary Peritoneal Cancer
Authors: C. Aghajanian, D.S. Dizon, P. Sabbatini, J.J. Raizer, J. Dupont, D.R. Spriggs
Journal: Journal of Clinical Oncology (2005)

To determine the maximum-tolerated dose, pharmacodynamics, and safety of the combination of bortezomib and carboplatin in recurrent ovarian cancer.Fifteen patients were treated with a fixed dose of carboplatin (area under the curve [AUC] 5) and increasing doses of bortezomib (0.75, 1, 1.3, and 1.5 mg/m2/dose). Patients must have received upfront chemotherapy and up to two prior chemotherapy regimens for recurrent disease. Neurologic evaluation was performed at baseline and after every two cycles by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire and examination by an attending neurologist. All patients received carboplatin alone in cycle 1 to establish baseline pharmacodynamics for nuclear factor-kappa B (NF-kB). Starting with cycle 2, patients were treated with carboplatin on day 1 and bortezomib on days 1, 4, 8, and 11.Diarrhea, rash, neuropathy, and constipation (with colonic wall thickening on computed tomography) were dose-limiting toxicities, occurring in the two patients treated at the 1.5 mg/m2/dose level. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire was helpful in guiding the need for dose reductions. Neurotoxicity was manageable through six cycles, with appropriate dose reductions. Carboplatin had no effect on bortezomib pharmacodynamics as measured by percent inhibition of the 20S proteasome. Bortezomib decreased carboplatin-induced NF-kB. The overall response rate to this combination was 47%, with two complete responses (CR) and five partial responses, including one CR in a patient with platinum-resistant disease.The recommended phase II dose of bortezomib administered in combination with carboplatin (AUC 5) is 1.3 mg/m2/dose.
Effect of PCI on Quality of Life in Patients with Stable Coronary Disease
Authors: William S. Weintraub, John A. Spertus, Paul Kolm, David J. Maron, Zefeng Zhang, Claudine Jurkovitz, Wei Zhang, Pamela M. Hartigan, Cheryl Lewis, Emir Veledar, Jim Bowen, Sandra B. Dunbar, Christi Deaton, Stanley Kaufman, Robert A. O'Rourke, Ron Goeree, Paul G. Barnett, Koon K. Teo, William E. Boden
Journal: New England Journal of Medicine (2008)

It has not been clearly established whether percutaneous coronary intervention (PCI) can provide an incremental benefit in quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease.We randomly assigned 2287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone. We assessed angina-specific health status (with the use of the Seattle Angina Questionnaire) and overall physical and mental function (with the use of the RAND 36-item health survey [RAND-36]).At baseline, 22% of the patients were free of angina. At 3 months, 53% of the patients in the PCI group and 42% in the medical-therapy group were angina-free (P<0.001). Baseline mean (+/-SD) Seattle Angina Questionnaire scores (which range from 0 to 100, with higher scores indicating better health status) were 66+/-25 for physical limitations, 54+/-32 for angina stability, 69+/-26 for angina frequency, 87+/-16 for treatment satisfaction, and 51+/-25 for quality of life. By 3 months, these scores had increased in the PCI group, as compared with the medical-therapy group, to 76+/-24 versus 72+/-23 for physical limitation (P=0.004), 77+/-28 versus 73+/-27 for angina stability (P=0.002), 85+/-22 versus 80+/-23 for angina frequency (P<0.001), 92+/-12 versus 90+/-14 for treatment satisfaction (P<0.001), and 73+/-22 versus 68+/-23 for quality of life (P<0.001). In general, patients had an incremental benefit from PCI for 6 to 24 months; patients with more severe angina had a greater benefit from PCI. Similar incremental benefits from PCI were seen in some but not all RAND-36 domains. By 36 months, there was no significant difference in health status between the treatment groups.Among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small, but significant, incremental benefits that disappeared by 36 months. (ClinicalTrials.gov number, NCT00007657.)