tbuckley/cabot-search huggingface dataset:
Adoption of Gene Expression Profile Testing and Association With Use of Chemotherapy Among Women With Breast Cancer
Authors: Michael J. Hassett, Samuel M. Silver, Melissa E. Hughes, Douglas W. Blayney, Stephen B. Edge, James G. Herman, Clifford A. Hudis, P. Kelly Marcom, Jane E. Pettinga, David Share, Richard Theriault, Yu-Ning Wong, Jonathan L. Vandergrift, Joyce C. Niland, Jane C. Weeks
Journal: Journal of Clinical Oncology (2012)

Purpose Gene expression profile (GEP) testing is a relatively new technology that offers the potential of personalized medicine to patients, yet little is known about its adoption into routine practice. One of the first commercially available GEP tests, a 21-gene profile, was developed to estimate the benefit of adjuvant chemotherapy for hormone receptor–positive breast cancer (HR-positive BC). Patients and Methods By using a prospective registry data set outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers, we assessed GEP test adoption and the association between testing and chemotherapy use. Results Of 7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time, testing increased (14.7% in 2006 to 27.5% in 2008; P &lt; .01) and use of chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P &lt; .01). Characteristics independently associated with lower odds of testing included African American versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76). Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70; 95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node-negative cancers, testing was associated with higher odds of chemotherapy use (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node-negative cancers, testing was associated with lower odds of chemotherapy use (OR, 0.11; 95% CI, 0.07 to 0.17). Conclusion There has been a progressive increase in use of this GEP test and an associated shift in the characteristics of and overall reduction in the proportion of women with HR-positive BC receiving adjuvant chemotherapy.
Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
Authors: Louise van der Weyden, Mark J Arends, Alistair G Rust, George Poulogiannis, Rebecca E McIntyre, David J Adams
Journal: Molecular Cancer (2012)

CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to the spontaneous development of tumors at an earlier age and an increased tumor incidence of predominantly lymphomas, but also some solid tumors. Tumorigenesis was accelerated after irradiation of Cadm1 mice, with the reduced latency in tumor formation suggesting there are genes that collaborate with loss of Cadm1 in tumorigenesis. To identify these co-operating genetic events, we performed a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Cadm1 mice, and identified several common insertion sites (CIS) found specifically on a Cadm1-null background (and not wildtype background). We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in tumorigenesis when Cadm1-expression is lost.
Intensity and physiological responses to the six-minute walk test in middle-aged and older adults: A comparison with cardiopulmonary exercise testing
Authors: Evandro Sperandio, Agatha Matheus, Vinícius Lauria, Flávio Almeida, David Santos, Rodrigo Pereira, Vítor Almeida, Mayara Silveira, Marcelo Romiti, Antônio Gagliardi, Rodolfo Arantes, Victor Dourado
Journal: European Respiratory Journal (2014)

The 6-min walk test (6MWT) is a simple filed walking test and widely used in clinical settings to assess functional exercise capacity. However, studies with healthy subjects are scarce. We hypothesized that the 6MWT may be useful to assess exercise capacity in healthy subjects. The purpose of this study was to evaluate the intensity and the physiological responses to the 6MWT comparing them with the responses obtained during cardiopulmonary exercise testing (CPET) in middle-aged and older adults. Seventy-four participants (40-74 years, 28 ± 6 kg/m 2 ), 37 men and 37 women, performed the 6MWT according to ATS guidelines. Physiological responses were evaluate during the 6MWT by means of a telemetry gas analyzer (K4b2, COSMED). The 6-min walk distance (6MWD) was recorded in meters. The subjects also performed in a different ocasion, a ramp protocol CPET on a treadmill. Peak V9O 2  in 6MWT corresponded to 78 ± 13% of the peak V9O 2  in CPET and the maximum heart rate corresponding to 80 ± 23% of that obtained in CPET. The peak V9O 2  in CPET was adequately predicted by 6MWD by the following linear regression equation: V9O 2mL/min/kg  = - 2,863 + (0,0563 x 6MWD m ) (R 2  = 0.76). The 6MWT represents a moderate to high intensity test in middle-aged and older adults and proved to be useful for predicting cardiorespiratory fitness in the present study. Our results suggest that the 6MWT may be useful also in asymptomatic individuals and its use in walk-based conditioning programs should be encouraged.
The economic impact of high-need psoriasis in daily clinical practice before and after the introduction of biologics
Authors: R.J.B. Driessen, L.A. Bisschops, E.M.M. Adang, A.W. Evers, P.C.M. Van De Kerkhof, E.M.G.J. De Jong
Journal: British Journal of Dermatology (2010)

Although costs of biologics are high, effective treatment of patients with psoriasis may reduce the total health care costs, as it may limit the need for hospitalization.To investigate the economic impact of psoriasis, including direct costs, before and after the introduction of biologics, with special focus on hospitalized patients, treatment effectiveness and patient satisfaction with medication.A descriptive retrospective cohort study including 67 patients with high-need psoriasis was done. Direct costs were investigated for the biologic and pre-biologic period. Direct costs for a subgroup of hospitalized patients were analysed separately. Patient satisfaction with biologic treatment was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version II. Effectiveness of biologic therapy was investigated by means of the Psoriasis Area and Severity Index (PASI).Mean total direct costs were €10,146 per patient per year (PPPY) in the pre-biologic treatment period, compared with €17,712 PPPY in the biologic treatment period. For six patients in the cohort, introduction of biologics led to a reduction of direct costs, as these patients did not need long hospitalizations. Treatment with biologics led to a decrease in PASI from 19·0 at the start of biologic therapy to 6·4 at analysis (66·4%). Patient satisfaction with biologics was high, indicated by a mean TSQM score of 77·8.Introduction of biologic therapies may have cost-neutral or cost-saving effects for patients who otherwise require long hospitalization periods. Treatment with biologics proved effective and was accompanied by high satisfaction for the patients.
Increased Albumin and Fibrinogen Synthesis in Hemodialysis Patients with Normal Nutritional Status
Authors: MAURO GIORDANO, PIERPAOLO DE FEO, PAOLA LUCIDI, EMANUELA dePASCALE, GELSOMINA GIORDANO, LORENA INFANTONE, ANNA MARIA ZOCCOLO, PIETRO CASTELLINO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. This study compared the rates of whole-body proteolysis and of albumin and fibrinogen synthesis of seven hemodialysis patients (HD) with those of seven normal matched control subjects (C). HD patients had a normal nutritional and inflammatory status and serum albumin levels &gt;3.5 g/dl. Endogenous leucine flux, albumin and fibrinogen fractional synthesis rate (FSR), and absolute intravascular synthesis rate (ASR) of albumin and fibrinogen all were evaluated by a primed/continuous infusion of 5,5,5-D3-L-leucine. Plasma volume was determined by the Evans blue dye dilution method. Endogenous leucine flux was significantly increased in HD (2.64 ± 0.08 μmol/kg per min) compared with C (2.17 ± 0.07 μmol/kg per min, P &lt; 0.05). Serum albumin concentrations were similar in HD and C. Plasma fibrinogen levels were significantly increased in HD compared with C ( P &lt; 0.05). Plasma volume was greater in HD than in C ( P &lt; 0.05). As a result, total intravascular pool of both albumin (141 ± 7 versus 114 ± 3 g/1.73 m 2 , P &lt; 0.05) and fibrinogen (11.7 ± 1 versus 6.7 ± 0.5 g/1.73 m 2 , P &lt; 0.05) were greater in HD than in C. Albumin FSR was not statistically different in HD and C. However, albumin ASR was significantly increased in HD than in C (13.7 ± 2 versus 10.3 ± 1 g/1.73 m 2 per d, P &lt; 0.05). Similarly, FSR of fibrinogen did not differ in HD and C groups, whereas ASR of fibrinogen was significantly higher in HD than in C (3.31 ± 0.6 versus 1.94 ± 0.3 g/1.73 m 2 per d, P &lt; 0.05). In summary, normoalbuminemic HD patients have an increased intravascular pool with a greater absolute synthesis rate of both albumin and fibrinogen and an increased rate of whole-body leucine flux.
Osteopontin increases heme oxygenase–1 expression and subsequently induces cell migration and invasion in glioma cells
Authors: Dah-Yuu Lu, Wei-Lan Yeh, Ssu-Ming Huang, Chih-Hsin Tang, Hsiao-Yun Lin, Shao-Jiun Chou
Journal: Neuro-Oncology (2012)

Malignant gliomas are associated with high morbidity and mortality because they are highly invasive into surrounding brain tissue, making complete surgical resection impossible. Osteopontin is abundantly expressed in the brain and is involved in cell adhesion, migration, and invasion. The aim of the present study was to investigate the mechanisms of glioma cell migration. Migration and invasion activity were determined by transwell and wound-healing assays. Gene and protein expressions were analyzed by reverse transcription-PCR, real time-PCR, and Western blotting. Nrf2-DNA binding activity was determined by electrophoretic mobility shift assay. Establishment of migration-prone sublines were performed to select highly migratory glioma. An intracranial xenograft mouse model was used for the in vivo study. Application of recombinant human osteopontin enhanced the migration of glioma cells. Expression of heme oxygenase (HO)-1 mRNA and protein also increased in response to osteopontin stimulation. Osteopontin-induced increase in cell migration was antagonized by HO-1 inhibitor or HO-1 small interfering (si)RNA. Osteopontin-mediated HO-1 expression was reduced by treatment with MEK/ERK and phosphatidylinositol 3-kinase/Akt inhibitors, as well as siRNA against Nrf2. Furthermore, osteopontin stimulated Nrf2 accumulation in the nucleus and increased Nrf2-DNA binding activity. In migration-prone sublines, cells with greater migration ability had higher osteopontin and HO-1 expression, and zinc protoporphyrin IX treatment could effectively reduce the enhanced migration ability. In an intracranial xenograft mouse model, transplantation of migration-prone subline cells exhibited higher cell migration than parental tumor cells. These results indicate that osteopontin activates Nrf2 signaling, resulting in enhanced HO-1 expression and cell migration in glioma cells.
Health related quality of life in people with advanced chronic liver disease
Authors: James G. Orr, Tara Homer, Laura Ternent, Julia Newton, Calum J. McNeil, Mark Hudson, David E.J. Jones
Journal: Journal of Hepatology (2014)

Cirrhosis has a long natural history with considerable symptomatic impacts, particularly in advancing disease. Measuring health related quality of life (HRQOL) in liver disease provides detail about the nature and extent of its effects on individuals. Understanding the drivers of impaired HRQOL can help identify targets for improvement through new treatments or health systems service delivery. Evaluation of novel therapies which target symptomatic improvement, should be done with suitable outcome measures, including HRQOL assessment. In this article, we provide an overview of HRQOL in advanced liver disease for the clinician. A clear description of the important HRQOL tools is given alongside a discussion of the factors, which are known to contribute to impaired HRQOL in advanced liver disease.
Detection of Flow Limitation with a Nasal Cannula/ Pressure Transducer System
Authors: JEAN-JACQUES HOSSELET, ROBERT G. NORMAN, INDU AYAPPA, DAVID M. RAPOPORT
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We previously showed that upper airway resistance can be inferred from the inspiratory flow contour during continuous positive airway pressure (CPAP) titration in obstructive sleep apnea syndrome (OSAS). The present study examines whether similar information can be obtained from inspiratory flow measured by a nasal cannula/pressure transducer. Ten symptomatic patients (snoring, upper airway resistance syndrome [UARS], or OSAS) and four asymptomatic subjects underwent nocturnal polysomnography (NPSG) with monitoring of flow (nasal cannula) and respiratory driving pressure (esophageal or supraglottic catheter). For each breath the inspiratory flow signal was classified as normal, flattened, or intermediate by custom software. "Resistance" was calculated from peak inspiratory flow and pressure, and normalized to the resistance during quiet wakefulness. Resistance in all stages of sleep was increased for breaths with flattened (387 ± 188%) or intermediate (292 ± 163%) flow contour. In combination with apnea–hypopnea index (AHI), identification of "respiratory events," consisting of consecutive breaths with a flattened contour, allowed differentiation of symptomatic from asymptomatic subjects. Our data show that development of a plateau on the inspiratory flow signal from a nasal cannula identifies increased upper airway resistance and the presence of flow limitation. In patients with symptoms of excessive daytime somnolence and low AHI this may help diagnose the UARS and separate it from nonrespiratory causes of sleep fragmentation.
Overexpression of the Nuclear Receptor Coactivator <b> <i>AIB1</i> </b> (<b> <i>SRC-3</i> </b>) during Progression of Pancreatic Adenocarcinoma
Authors: Ralf Thorsten Henke, Bassem R. Haddad, Sung Eun Kim, Janice Dalby Rone, Aparna Mani, John Milburn Jessup, Anton Wellstein, Anirban Maitra, Anna Tate Riegel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) was found to be amplified and overexpressed in breast and some other epithelial tumors. We have reported that expression of AIB1 is rate limiting for growth factor, as well as hormone signaling. Here, we assess the involvement of AIB1 in the development of pancreatic adenocarcinoma. Experimental Design: We investigated expression levels of AIB1 protein and mRNA in pancreatic cancer cell lines and in a series of archival pancreatic adenocarcinoma (n = 78), pancreatic intraepithelial neoplasia (n = 93), pancreatitis (n = 28), and normal pancreas tissues (n = 52). We also determined AIB1 gene copy numbers by fluorescence in situ hybridization in a subset of cases. Results: In normal pancreas ducts, we rarely found detectable levels of AIB1 mRNA or protein (&amp;lt;6% of the samples). In pancreatitis and low-grade intraepithelial neoplasia, we found an increased frequency of AIB1 expression (&amp;gt;14 and &amp;gt;23%, respectively) relative to normal tissues (P &amp;lt; 0.01). Adenocarcinoma, as well as high-grade intraepithelial neoplasia, showed increased levels as well as the highest frequency of AIB1 expression with &amp;gt;65% of samples positive for mRNA and protein (P &amp;lt; 0.0001 relative to the other groups). An increased copy number of the AIB1 gene, observed in 37% of cancers, may account for a portion of the increase in expression. Conclusions: AIB1 overexpression is frequent in pancreatic adenocarcinoma and its precursor lesions. On the basis of its rate-limiting role for the modulation of growth factor signals, we propose a major role of AIB1 in the multistage progression of pancreatic cancer.
The Role of Behavioral Science Theory in Development and Implementation of Public Health Interventions
Authors: Karen Glanz, Donald B. Bishop
Journal: Annual Review of Public Health (2010)

Increasing evidence suggests that public health and health-promotion interventions that are based on social and behavioral science theories are more effective than those lacking a theoretical base. This article provides an overview of the state of the science of theory use for designing and conducting health-promotion interventions. Influential contemporary perspectives stress the multiple determinants and multiple levels of determinants of health and health behavior. We describe key types of theory and selected often-used theories and their key concepts, including the health belief model, the transtheoretical model, social cognitive theory, and the ecological model. This summary is followed by a review of the evidence about patterns and effects of theory use in health behavior intervention research. Examples of applied theories in three large public health programs illustrate the feasibility, utility, and challenges of using theory-based interventions. This review concludes by identifying cross-cutting themes and important future directions for bridging the divides between theory, practice, and research.
Two Genome-wide Association Studies of Aggressive Prostate Cancer Implicate Putative Prostate Tumor Suppressor Gene DAB2IP
Authors: D. Duggan, S. L. Zheng, M. Knowlton, D. Benitez, L. Dimitrov, F. Wiklund, C. Robbins, S. D. Isaacs, Y. Cheng, G. Li, J. Sun, B.-L. Chang, L. Marovich, K. E. Wiley, K. Balter, P. Stattin, H.-O. Adami, M. Gielzak, G. Yan, J. Sauvageot, W. Liu, J. W. Kim, E. R. Bleecker, D. A. Meyers, B. J. Trock, A. W. Partin, P. C. Walsh, W. B. Isaacs, H. Gronberg, J. Xu, J. D. Carpten
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundThe consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment.
No Evidence for Correlation of <i>DDX1</i> Gene Amplification With Improved Survival Probability in Patients With <i>MYCN</i>-Amplified Neuroblastomas
Authors: Katleen De Preter, Frank Speleman, Valérie Combaret, John Lunec, Julian Board, Andy Pearson, Anne De Paepe, Nadine Van Roy, Geneviève Laureys, Jo Vandesompele
Journal: Journal of Clinical Oncology (2005)

demonstrating a rate of 48% and Weitzel et al 3 indicating a rate of 100%.This discrepancy may reflect the low number of carriers in their study, geographical variation, differences in directiveness of genetic counseling, or other factors related to patient decision making.Finally, we agree that there are currently issues of feasibility associated with rapid GCRA.For most newly diagnosed patients, the standard turnaround time of up to 3 weeks for BRCA1/2 test results should be sufficient.In addition, if research demonstrates patient interest and medical value of rapid GCRA, then rapid GCRA may become more feasible as the waiting time for results may decrease in the face of heightened demand.Furthermore, given the high rate of insurance reimbursement for genetic testing, preauthorization for BRCA1/2 testing is often not required, and when required can usually be obtained quickly.Patients also need to be aware that expedited testing is available (at additional cost), and that Ashkenazi Jewish patients undergoing mutation analysis for the three founder mutations may obtain results in less than 3 weeks.We are now in the process of examining many of these issues in an NIH-funded randomized trial of rapid GCRA versus "usual care" in highrisk newly diagnosed patients.In order to maximize the window of time that patients have to make informed decisions, high-risk patients should be identified at the time of breast biopsy or as quickly as possible following diagnosis so that GCRA can be rapidly delivered to interested patients.Ongoing research will be vital in developing genetic counseling and testing protocols that are appropriate for newly diagnosed breast cancer patients and which enhance informed patient decision making.
Tendon involvement in the feet of patients with gout: a dual-energy CT study
Authors: Nicola Dalbeth, Ramanamma Kalluru, Opetaia Aati, Anne Horne, Anthony J Doyle, Fiona M McQueen
Journal: Annals of the Rheumatic Diseases (2013)

To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT).Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites).MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6-10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001).Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.
Validation of the Chinese Version of the Problem Areas in Diabetes (PAID-C) Scale
Authors: Min-Feng Huang, Mary Courtney, Helen Edwards, Jan McDowell
Journal: Diabetes Care (2009)

OBJECTIVE To examine the psychometric properties of a Chinese version of the Problem Areas In Diabetes (PAID-C) scale. RESEARCH DESIGN AND METHODS The reliability and validity of the PAID-C were evaluated in a convenience sample of 205 outpatients with type 2 diabetes. Confirmatory factor analysis, Bland-Altman analysis, and Spearman's correlations facilitated the psychometric evaluation. RESULTS Confirmatory factor analysis confirmed a one-factor structure of the PAID-C (χ2/df ratio = 1.894, goodness-of-fit index = 0.901, comparative fit index = 0.905, root mean square error of approximation = 0.066). The PAID-C was associated with A1C (rs = 0.15; P &amp;lt; 0.05) and diabetes self-care behaviors in general diet (rs = −0.17; P &amp;lt; 0.05) and exercise (rs = −0.17; P &amp;lt; 0.05). The 4-week test-retest reliability demonstrated satisfactory stability (rs = 0.83; P &amp;lt; 0.01). CONCLUSIONS The PAID-C is a reliable and valid measure to determine diabetes-related emotional distress in Chinese people with type 2 diabetes.