tbuckley/cabot-search huggingface dataset:
STAT3 Expression, Molecular Features, Inflammation Patterns, and Prognosis in a Database of 724 Colorectal Cancers
Authors: Teppei Morikawa, Yoshifumi Baba, Mai Yamauchi, Aya Kuchiba, Katsuhiko Nosho, Kaori Shima, Noriko Tanaka, Curtis Huttenhower, David A. Frank, Charles S. Fuchs, Shuji Ogino
Journal: Clinical Cancer Research (2011)

Abstract Purpose: STAT3 is a transcription factor that is constitutively activated in some cancers. It seems to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular, or prognostic features of STAT3-activated colorectal cancer remain uncertain. Experimental Design: Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. The Cox proportional hazards model was used to compute mortality HR, adjusting for clinical, pathologic, and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q LOH, TP53 (p53), CTNNB1 (β-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations. Results: Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer–specific mortality [log-rank P = 0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative): 1.85, 95% CI: 1.30–2.63, Ptrend = 0.0005; multivariate HR: 1.61, 95% CI: 1.11–2.34, Ptrend = 0.015]. p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate OR: 3.23; 95% CI: 1.89–5.53, P &amp;lt; 0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation. Conclusions: STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. Clin Cancer Res; 17(6); 1452–62. ©2011 AACR.
The Effect of Primary Care Provider Turnover on Patient Experience of Care and Ambulatory Quality of Care
Authors: Ashok Reddy, Craig E. Pollack, David A. Asch, Anne Canamucio, Rachel M. Werner
Journal: JAMA Internal Medicine (2015)

Primary care provider (PCP) turnover is common and can disrupt patient continuity of care. Little is known about the effect of PCP turnover on patient care experience and quality of care.To measure the effect of PCP turnover on patient experiences of care and ambulatory care quality.Observational, retrospective cohort study of a nationwide sample of primary care patients in the Veterans Health Administration (VHA). We included all patients enrolled in primary care at the VHA between 2010 and 2012 included in 1 of 2 national data sets used to measure our outcome variables: 326,374 patients in the Survey of Healthcare Experiences of Patients (SHEP; used to measure patient experience of care) associated with 8441 PCPs and 184,501 patients in the External Peer Review Program (EPRP; used to measure ambulatory care quality) associated with 6973 PCPs.Whether a patient experienced PCP turnover, defined as a patient whose provider (physician, nurse practitioner, or physician assistant) had left the VHA (ie, had no patient encounters for 12 months).Five patient care experience measures (from SHEP) and 11 measures of quality of ambulatory care (from EPRP).Nine percent of patients experienced a PCP turnover in our study sample. Primary care provider turnover was associated with a worse rating in each domain of patient care experience. Turnover was associated with a reduced likelihood of having a positive rating of their personal physician of 68.2% vs 74.6% (adjusted percentage point difference, -5.3; 95% CI, -6.0 to -4.7) and a reduced likelihood of getting care quickly of 36.5% vs 38.5% (adjusted percentage point difference, -1.1; 95% CI, -2.1 to -0.1). In contrast, PCP turnover was not associated with lower quality of ambulatory care except for a lower likelihood of controlling blood pressure of 78.7% vs 80.4% (adjusted percentage point difference, -1.44; 95% CI, -2.2 to -0.7). In 9 measures of ambulatory care quality, the difference between patients who experienced no PCP turnover and those who had a PCP turnover was less than 1 percentage point. These effects were moderated by the patients' continuity with their PCP prior to turnover, with a larger detrimental effect of PCP turnover among those with higher continuity prior to the turnover.Primary care provider turnover was associated with worse patient experiences of care but did not have a major effect on ambulatory care quality.
Pericardial modulation of right and left ventricular diastolic interaction.
Authors: J Spadaro, O H Bing, W H Gaasch, R M Weintraub
Journal: Circulation Research (1981)

We studied the effects of the right ventricle (RV) and pericardium on left ventricular (LV) diastolic pressure-volume (P-V) relations in the normothermic isolated blood-perfused dog heart. Studies were performed at a constant heart rate (atrial pacing at 120 beats/min) with a coronary perfusion pressure of 100 mm Hg. LV volume was directly controlled by an intraventricular balloon, whereas RV filling pressure was increased stepwise from zero to 20 mm Hg. During progressive increases in RV filling pressure, with the pericardium intact, the LV diastolic P-V relations were shifted up and to the left; this leftward shift of the LV diastolic P-V relation was associated with an increase in the modulus of LV chamber stiffness. Closing the small pericardial incisions with sutures significantly increased this effect. In the absence of the pericardium, progressive filling of the RV resulted in minor changes in LV diastolic P-V relations. Only when the RV filling pressure was markedly elevated (20 mm Hg) was there a significant effect on LV diastolic pressure. The pericardium has a small but significant effect on LV diastolic P-V relations at physiological RV filling pressures, and this effect becomes considerable at high RV filling pressures. The RV influence on LV diastolic P-V relations is significantly modulated by the presence of tightness of the pericardium.
Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment
Authors: Rachael J L Tan, Laura J Gibbons, Catherine Potter, Kimme L Hyrich, Ann W Morgan, Anthony G Wilson, John D Isaacs, Anne Barton
Journal: Annals of the Rheumatic Diseases (2010)

Anti-tumour necrosis factor (anti-TNF) therapy has proved to be highly successful in treating rheumatoid arthritis (RA), although 30-40% of patients have little or no response. The authors hypothesise that this may be genetically determined. In other complex diseases, susceptibility genes have been shown to influence treatment response. The aim of the current study was to investigate the association of markers within confirmed RA susceptibility loci with the response to anti-TNF treatment.Eighteen single nucleotide polymorphisms (SNPs) mapping to 11 genetic loci were genotyped in 1012 patients with RA receiving treatment with etanercept, infliximab or adalimumab. Multivariate linear regression analyses were performed using the absolute change in 28 joint count disease activity score (DAS28) between baseline and 6-month follow-up as the outcome variable, adjusting for confounders. p Values <0.05 were considered statistically significant and associated markers were genotyped in an additional 322 samples. Analysis was performed in the combined cohort of 1334 subjects with RA treated with anti-TNF.In the combined analysis, SNPs mapping to AFF3 and CD226 had a statistically significant association with the response to anti-TNF treatment under an additive model. The G allele at rs10865035, mapping to AFF3, was associated with an improved response to anti-TNF treatment (coefficient -0.14 (95% CI -0.25 to -0.03), p=0.015). At the CD226 SNP rs763361, the C allele conferred reduced response to treatment (coefficient 0.11 (95% CI 0.00 to 0.22), p=0.048).These results suggest that AFF3 and CD226, two confirmed RA susceptibility genes, have an additional role in influencing the response to anti-TNF treatment.
Chronic myelogenous leukemia and sweet syndrome
Authors: Philip R. Cohen, Razelle Kurzrock
Journal: American Journal of Hematology (1989)

Abstract We report a 64‐year‐old woman with chronic myelogenous leukemia of 3 years duration who developed Sweet syndrome. Improvement in her blood counts after hydroxyurea was not associated with a decrease in size of the skin lesions. However, the cutaneous lesions of Sweet syndrome quickly resolved with systemic prednisone. Sweet syndrome has only been documented in the literature for five other chronic myelogenous leukemia patients. The characteristics, treatment, and differential diagnosis of this disorder in chronic myelogenous leukemia patients are reviewed.
Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites
Authors: Oswald Steward, Christopher S Wallace, Gregory L Lyford, Paul F Worley
Journal: Neuron (1998)

Polyribosomal complexes beneath postsynaptic sites on dendrites provide a substrate for local translation of particular mRNAs, but the signals that target mRNAs to synapses remain to be defined. Here, we report that high frequency activation of the perforant path projections to the dentate gyrus causes newly synthesized mRNA for the immediate-early gene (IEG) Arc to localize selectively in activated dendritic segments. Newly synthesized Arc protein also accumulates in the portion of the dendrite that had been synaptically activated. The targeting of Arc mRNA was not disrupted by locally inhibiting protein synthesis, indicating that the signals for mRNA localization reside in the mRNA itself. This novel mechanism through which newly synthesized mRNA is precisely targeted to activated synapses is well suited to play a role in the enduring forms of activity-dependent synaptic modification that require protein synthesis.
1312 ABNORMAL PRIMARY CILIA IN CHOLANGIOCYTES CAUSE CHOLESTATIC LIVER DISEASE IN HNFlβ DELETION IN HUMANS
Authors: P. Roelandt, A. Antoniou, W. Laleman, C. Verslype, W. Van Steenbergen, F. Nevens, R. De Vos, F. Lemaigre, D. Cassiman
Journal: Journal of Hepatology (2011)
Comparison of stratified primary care management for low back pain with current best practice (STarT Back): a randomised controlled trial
Authors: Jonathan C Hill, David GT Whitehurst, Martyn Lewis, Stirling Bryan, Kate M Dunn, Nadine E Foster, Kika Konstantinou, Chris J Main, Elizabeth Mason, Simon Somerville, Gail Sowden, Kanchan Vohora, Elaine M Hay
Journal: The Lancet (2011)
Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer
Authors: S Vitale, B Cambien, B F Karimdjee, R Barthel, P Staccini, C Luci, V Breittmayer, F Anjuere, A Schmid-Alliana, H Schmid-Antomarchi
Journal: Gut (2006)

Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two orthotopic models of metastatic colon cancer (liver and lung) and in the standard subcutaneous model.We have developed models of skin tumours, liver and pulmonary metastasis and compared the extent of tumour development between C26 colon cancer cells expressing either the native, the soluble, the membrane-bound fractalkine or none.The native fractalkine exhibits the strongest antitumour effect, reducing the tumour size by 93% in the skin and by 99% in the orthotopic models (p<0.0001). Its overall effect results from a critical balance between the activity of the secreted and the membrane-bound forms, balance that is itself dependent on the target tissue. In the skin, both molecular variants reduce tumour development by 66% (p<0.01). In contrast, the liver and lung metastases are only significantly reduced by the soluble form (by 96%, p<0.002) whereas the membrane-bound variant exerts a barely significant effect in the liver (p = 0.049) and promotes tumour growth in the lungs. Moreover, we show a significant difference in the contribution of the infiltrating leukocytes to the tumour-suppressive activity of fractalkine between the standard and the orthotopic models.Fractalkine expression by C26 tumour cells drastically reduces their metastatic potential in the two physiological target organs. Both molecular forms contribute to its antitumour potential but exhibit differential effects on tumour development depending on the target tissue.
P208 Assessment Of Curvilinearity (curv) And Phase Iii Analysis Of Multiple Breath Washout (mbw)
Authors: S. Irving, A. Bush
Journal: Thorax (2014)

<h3>Introduction and Hypothesis</h3> In cystic fibrosis (CF), but not in PCD (Am J Respir Crit Care Med. 2013;188:545–549), lung clearance index (LCI) and spirometry are correlated. The difference may be related to differences in small airway disease. To explore this further, the novel MBW analyses Curv, S<sub>cond* </sub>and S<sub>acin*</sub> were calculated in PCD and CF (Eur Respir J. 2013;42(suppl 2):380–388). Curv assesses specific ventilation inhomogeneity calculated as the ratio of the slope of the first half to the second half of the washout, and unlike LCI is not sensitive to deadspace effects. S<sub>cond</sub> and S<sub>acin</sub> are not useful in severe obstructive lung disease; S<sub>cond*</sub> and S<sub>acin*</sub> are recalculations corresponding respectively to VI in the conducting airways and the acinar region. (S<sub>cond*</sub> is measured from the slopes of the increase in phase III modified to include the 0–3 lung turnovers and S<sub>acin*</sub>* is phase III over the first breath of the washout, minus the contribution of S<sub>cond*</sub>). We hypothesised that these novel indices will differ in PCD compared to CF due to differences in small airways disease. <h3>Methods</h3> 38 PCD (14 male, group mean (range) age 21.8 (7.2–59.1) years, FEV1 Z score -3.18 ((-6–0.17)) and CF (14 male, group mean (range) age 10.9 (6.8–19.1) years, FEV1 Z score -2.72 ((-5.4–0.9)) patients matched for P. aeruginosa status and 24 healthy controls recorded spirometry and MBW. LCI, Curv, Scond* and Sacin* were calculated. <h3>Results</h3> There was no difference in LCI, FEV<sub>1</sub> and Curv between the patient groups. LCI was correlated with S<sub>cond*</sub> (CF p = 0.0006, r = 0.5, PCD, p = 0.03 r = 0.3), S<sub>acin*</sub> (CF p &lt; 0.0001, r = 0.7, PCD p &lt; 0.0001, r = 0.6) and S<sub>acin</sub> (CF p &lt; 0.0001, r = 0.7, PCD p = 0.0003, r = 0.5), whereas S<sub>cond </sub>was not. There was no difference in S<sub>acin*</sub>* between the groups, but S<sub>cond*</sub> was significantly lower in PCD, approaching that of healthy controls. <h3>Conclusions</h3> Curv is similarly impaired in PCD and CF. S<sub>cond* </sub>is nearly normal in PCD but not CF, supporting the hypothesis that there are differences in distal airway disease between these conditions. Finally, the results suggest that the new indices may be better discriminators between diseases in severe obstructive lung disease.
Physical Activity and Survival After Prostate Cancer Diagnosis in the Health Professionals Follow-Up Study
Authors: Stacey A. Kenfield, Meir J. Stampfer, Edward Giovannucci, June M. Chan
Journal: Journal of Clinical Oncology (2011)

Purpose To determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death. Patients and Methods We evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death. Results Among men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (P trend &lt; .001) and PCa mortality (P trend = .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked ≥ 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with ≥ 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with ≥ 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P = .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk. Conclusion In men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for ≥ 3 hours a week may substantially improve PCa-specific survival.
The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses
Authors: J. C. Craig, G. J. Williams, M. Jones, M. Codarini, P. Macaskill, A. Hayen, L. Irwig, D. A. Fitzgerald, D. Isaacs, M. McCaskill
Journal: BMJ (2010)

<b>Objectives</b> To evaluate current processes by which young children presenting with a febrile illness but suspected of having serious bacterial infection are diagnosed and treated, and to develop and test a multivariable model to distinguish serious bacterial infections from self limiting non-bacterial illnesses. <b>Design </b>Two year prospective cohort study. <b>Setting </b>The emergency department of The Children’s Hospital at Westmead, Westmead, Australia. <b>Participants</b> Children aged less than 5 years presenting with a febrile illness between 1 July 2004 and 30 June 2006. <b>Intervention</b> A standardised clinical evaluation that included mandatory entry of 40 clinical features into the hospital’s electronic record keeping system was performed by physicians. Serious bacterial infections were confirmed or excluded using standard radiological and microbiological tests and follow-up. <b>Main outcome measures </b>Diagnosis of one of three key types of serious bacterial infection (urinary tract infection, pneumonia, and bacteraemia), and the accuracy of both our clinical decision making model and clinician judgment in making these diagnoses.<b></b> <b>Results</b> We had follow-up data for 93% of the 15 781 instances of febrile illnesses recorded during the study period. The combined prevalence of any of the three infections of interest (urinary tract infection, pneumonia, or bacteraemia) was 7.2% (1120/15 781, 95% confidence interval (CI) 6.7% to 7.5%), with urinary tract infection the diagnosis in 543 (3.4%) cases of febrile illness (95% CI 3.2% to 3.7%), pneumonia in 533 (3.4%) cases (95% CI 3.1% to 3.7%), and bacteraemia in 64 (0.4%) cases (95% CI 0.3% to 0.5%). Almost all (&gt;94%) of the children with serious bacterial infections had the appropriate test (urine culture, chest radiograph, or blood culture). Antibiotics were prescribed acutely in 66% (359/543) of children with urinary tract infection, 69% (366/533) with pneumonia, and 81% (52/64) with bacteraemia. However, 20% (2686/13 557) of children without bacterial infection were also prescribed antibiotics. On the basis of the data from the clinical evaluations and the confirmed diagnosis, a diagnostic model was developed using multinomial logistic regression methods. Physicians’ diagnoses of bacterial infection had low sensitivity (10-50%) and high specificity (90-100%), whereas the clinical diagnostic model provided a broad range of values for sensitivity and specificity. <b>Conclusions</b> Emergency department physicians tend to underestimate the likelihood of serious bacterial infection in young children with fever, leading to undertreatment with antibiotics. A clinical diagnostic model could improve decision making by increasing sensitivity for detecting serious bacterial infection, thereby improving early treatment.
A Double-Blind, Placebo-Controlled Trial of Sibutramine for Olanzapine-Associated Weight Gain
Authors: David C Henderson, Paul M Copeland, Tara B Daley, Christina P Borba, Corrine Cather, Dana D Nguyen, Pearl M Louie, A Eden Evins, Oliver Freudenreich, Doug Hayden, Donald C Goff
Journal: American Journal of Psychiatry (2005)

Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder.Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification.The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group.Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.