tbuckley/cabot-search huggingface dataset:
MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1
Authors: Dengbo Ji, Zhiguo Chen, Ming Li, Tiancheng Zhan, Yunfeng Yao, Zhiqian Zhang, Jianzhong Xi, Li Yan, Jin Gu
Journal: Molecular Cancer (2014)

Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer. Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models. miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin. Our data demonstrate that miR-181a expression is associated with CRC liver metastasis and survival. miR-181a has strong tumor-promoting effects through inhibiting the expression of WIF-1, and its potential role in promoting epithelial-mesenchymal transition.
The Resident in Community Psychiatry: An Assessment of Changes in Knowledge and Attitudes
Authors: MARIETTA BABCOCK KOLMER, HOWARD M. KERN
Journal: American Journal of Psychiatry (1968)

The authors wished to determine the effect of a training program in community psychiatry on the attitudes of psychiatric residents. Using structured interviews with 12 psychiatric residents prior to, during, and at the end of a one-year training program, they found that seven of the 11 trainees who completed the study showed a statistically significant positive change in their knowledge of and attitudes toward community mental health practice.
Subcutaneous Glucose Monitoring
Authors: W. Kenneth Ward
Journal: Diabetes Care (2002)

This letter is in response to the study by Jungheim et al. (1) in the September issue of Diabetes Care . They studied a subcutaneous glucose monitoring system in 23 subjects with diabetes over a 3-day period. They report a satisfactory mean absolute difference (MAD) between sensor values and capillary blood glucose of 14.8%.

I agree with the authors that their sensor, which uses microdialysis, appears to function in a stable fashion. It is impressive that they found it necessary to calibrate the device only once during this period, at a mean time of 4.7 h after insertion. …
Apolipoprotein A-IV Serum Concentrations Are Elevated in Patients with Mild and Moderate Renal Failure
Authors: Florian Kronenberg, Erich Kuen, Eberhard Ritz, Paul Ko[Combining Diaeresis]nig, Gu[Combining Diaeresis]nter Kraatz, Karl Lhotta, Johannes F. E. Mann, Gerhard A. Mu[Combining Diaeresis]ller, Ulrich Neyer, Werner Riegel, Peter Riegler, Vedat Schwenger, Arnold von Eckardstein
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cell culture studies and investigations in mice that overexpress either human or mouse apolipoprotein A-IV (apoA-IV) revealed anti-atherogenic properties of apoA-IV. An association between low apoA-IV concentrations and coronary artery disease in humans was demonstrated; therefore, apoA-IV may also play an antiatherogenic role in humans. Because apoA-IV is markedly elevated in dialysis patients, patients with the earliest and modest stages of renal impairment were studied to assess the association of apoA-IV with GFR and atherosclerotic complications. GFR was measured by the use of iohexol in 227 non-nephrotic patients with different degrees of renal impairment. ApoA-IV increased significantly with decreasing GFR and was already elevated in earliest stages of renal disease (GFR > 90 ml/min per 1.73 m2). Multiple linear regression analysis identified renal function parameters (GFR, creatinine, and urea) as the most important determinants of apoA-IV levels in serum of these patients. Twenty-six patients had already experienced 36 atherosclerotic events. Logistic regression analysis identified three variables associated with atherosclerotic complications: age, apoA-IV, and gender. Each 1 mg/dl increase of apoA-IV decreased the odds ratio for an atherosclerotic complication by 8% (P = 0.011). The data clearly show that the anti-atherogenic apoA-IV starts to increase during the earliest phases of renal insufficiency, which makes apoA-IV an early marker of renal impairment.
Prospective Association Between Inflammatory Markers and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes
Authors: Amy C. Alman, Gregory L. Kinney, Russell P. Tracy, David M. Maahs, John E. Hokanson, Marian J. Rewers, Janet K. Snell-Bergeon
Journal: Diabetes Care (2013)

The role of inflammation in the increased risk of cardiovascular disease in type 1 diabetes is unclear. We examined the association of inflammation and progression of coronary artery calcification (CAC)-a marker of subclinical atherosclerosis-in adults with and without type 1 diabetes.A nested case-control study was performed within the prospective cohort of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Participants underwent two CAC measurements ~2.5 years apart. Case subjects (n = 204) were those with significant progression of CAC. Control subjects (n = 258) were frequency-matched to case subjects on diabetes status, sex, age, and baseline CAC status. Inflammatory marker assessments were performed on stored blood samples from baseline. A principal components analysis (PCA) was performed and a composite score derived from that analysis. The composite score was constructed by assigning a value of 1 for each PCA component where at least one of the markers exceeded the 75th percentile (range 0-4). Conditional logistic regression was used for the matching strategy.The first two components of the PCA were modestly (odds ratio 1.38 [95% CI 1.08-1.77] and 1.27 [1.02-1.59], respectively) associated with CAC progression after adjustment for other risk factors. The composite score was more strongly associated with CAC progression for those with elevated markers in three or four of the principal components compared with those with none.Measures of inflammation were associated with progression of CAC in a population of adults with and without type 1 diabetes.
Rheumatic Heart Disease
Authors: Karen Sliwa, Peter Zilla
Journal: Circulation (2012)

R heumatic heart disease (RHD) remains one of the largest preventable burdens of disease in the world.It is perceived as a disease of childhood, acquired by streptococcal throat infection of the tonsillo-pharynx, leading to an inflammatory reaction that involves many organs, including the heart.However, cases in children of 5 to 14 years of age are likely to represent only 15% to 20% of all cases within all age groups of vulnerable populations. 1 Article see p 3127As a disease of poverty and low socioeconomic circumstances, RHD is prevalent in the developing world.This association with the poorest and weakest of society represents a double tragedy: whereas the lack of access to education, infrastructure, and medical facilities turns a preventable and surgically treatable condition into a major cause of suffering, incapacity, and death, global awareness remains depressingly low.Although RHD has received increasing attention in the past few years, leading to declarations, 2 definition of areas of research, 3 and new diagnostic criteria on echocardiography, as well as suggestions for prevention programs, insight into incidences, disease progression, and mortality remains largely speculative because of a lack of data.With the adoption of echocardiography to project-funded screening programs, it has emerged that previous estimates may have distinctly underestimated the prevalence of the disease. 4Because screening programs generally focus on school children, they concentrate on the most accessible and reliable cohort for the assessment of disease incidence.Yet, echo-based incidences of RHD in school children are agedependent, 5 because a 71% increase in children younger than 9 years of age, to those older than 12 years of age, 4 was shown.Although the 10ϫ higher sensitivity of echo screening over clinical assessment 4 detects in 90% of cases clinically silent RHD, almost half of these valve lesions are already functionally moderate to severe. 6Therefore, together
Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial
Authors: Anish Thomas, Arun Rajan, Arlene Berman, Yusuke Tomita, Christina Brzezniak, Min-Jung Lee, Sunmin Lee, Alexander Ling, Aaron J Spittler, Corey A Carter, Udayan Guha, Yisong Wang, Eva Szabo, Paul Meltzer, Seth M Steinberg, Jane B Trepel, Patrick J Loehrer, Giuseppe Giaccone
Journal: The Lancet Oncology (2015)
Disturbed Patterns of Immunocompetent Cells in Usual-Type Vulvar Intraepithelial Neoplasia
Authors: Manon van Seters, Ilse Beckmann, Claudia Heijmans-Antonissen, Marc van Beurden, Patricia C. Ewing, Freek J. Zijlstra, Theo J.M. Helmerhorst, Alex KleinJan
Journal: Cancer Research (2008)

Abstract Genital infection with human papillomavirus (HPV) is usually transient, as the immune system is capable of eliminating the virus. When immunity “fails” and the infection persists, vulvar intraepithelial neoplasia (VIN) may develop. In this study, we examined the distribution of inflammatory cells in 51 patients with HPV-associated usual-type VIN and in 19 healthy controls. Frozen vulvar tissue samples were tested for the presence of HPV-DNA, and immunohistochemical staining for the markers CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8, and CD25/HLA-DR was performed. Cells were counted in both the epidermis and dermis over at least 2 mm of basal membrane length. In the epidermis of VIN patients, CD1a+ and CD207+ (Langerin) dendritic cells (DC) and CD8+ T cells were significantly lower than in controls, whereas the number of CD123+/CD11c− plasmacytoid DCs (pDC) was significantly increased. No significant changes were observed for CD208+ DCs, CD94+ natural killer (NK) cells, CD4+ T cells, and CD25+/HLA-DR+ regulatory T cells. In the dermis of VIN patients, elevated numbers of CD208+, CD123+/CD11c−, CD94+, CD4+, CD8+, and CD25+/HLA-DR+ cells were observed when compared with healthy controls. The numbers of CD1a+ and CD207+ DCs were not different between groups. In summary, high-risk HPV–related usual-type VIN lesions are characterized by an immunosuppressive state in the epidermis, showing a reduction of immature myeloid DCs (mDC) and CD8+ T cells. In the dermis, inflammatory activation is reflected by the influx of mature mDCs and pDCs, NK cells, and T cells, suggesting that the cellular immune response on viral HPV infection occurs in the dermis of VIN patients. [Cancer Res 2008;68(16):6617–22]
Formulas Calculating Creatinine Clearance Are Inadequate for Determining Eligibility for Cisplatin-Based Chemotherapy in Bladder Cancer
Authors: Ganesh V. Raj, Alexia Iasonos, Harry Herr, Sherri Machele Donat
Journal: Journal of Clinical Oncology (2006)

Efficacy of formulas calculating creatinine clearance (CrCl) to determine renal function eligibility (CrCl > 60 mL/min) for cisplatin-based chemotherapy has not been examined adequately in the bladder cancer population. We hypothesize these formulas may underestimate measured CrCl, and therefore the eligibility for cisplatin-based chemotherapy.A database of 208 patients with unresectable or metastatic bladder cancer treated on protocol at Memorial Sloan-Kettering Cancer Center (New York, NY) with cisplatin-based chemotherapy between 1983 and 1994 was examined retrospectively. The association between measured and calculated CrCl and the ability to complete three cycles (minimum therapeutic) of chemotherapy was examined.Baseline measured CrCl was less than 60 mL/min in 16% compared with 12% to 44% using various formulas. Concordance between calculated and measured CrCl less than 60 mL/min was poor (range of kappa, 0.14 to 0.38). In patients older than age 65, 22% had a measured CrCl less than 60 mL/min, compared with 10% to 63% calculated using various formulas. Overall, 80% completed at least three cycles of cisplatin-based chemotherapy. The ability to complete at least three cycles was statistically significantly related with a measured CrCl more than 60 mL/min (P = .02), but not with calculated CrCl more than 60 mL/min.Current formulas estimating CrCl tend to underestimate measured CrCl, especially in those older than 65 years. Depending on the formula used, up to 44% who actually received cisplatin-based chemotherapy based on measured CrCl would be deemed ineligible at present, potentially affecting survival outcomes. Methodology for determining CrCl and/or renal eligibility for cisplatin-based chemotherapy in patients with bladder cancer should be re-examined.
A murine model of hereditary hemorrhagic telangiectasia
Authors: Annie Bourdeau, Daniel J. Dumont, Michelle Letarte
Journal: Journal of Clinical Investigation (1999)

Endoglin (CD105), an accessory protein of the TGF-beta receptor superfamily, is highly expressed on endothelial cells. Hereditary hemorrhagic telangiectasia type 1 (HHT1) is associated with mutations in the Endoglin gene, leading to haploinsufficiency. To generate a disease model and ascertain the role of endoglin in development, we generated mice lacking 1 or both copies of the gene. Endoglin null embryos die at gestational day 10.0-10.5 due to defects in vessel and heart development. Vessel formation appears normal until hemorrhage occurs in yolk sacs and embryos. The primitive vascular plexus of the yolk sac fails to mature into defined vessels, and vascular channels dilate and rupture. Internal bleeding is seen in the peritoneal cavity, implying fragile vessels. Heart development is arrested at day 9.0, and the atrioventricular canal endocardium fails to undergo mesenchymal transformation and cushion-tissue formation. These data suggest that endoglin is critical for both angiogenesis and heart valve formation. Some heterozygotes, either with an inbred 129/Ola or mixed C57BL/6-129/Ola background, show signs of HHT, such as telangiectases or recurrent nosebleeds. In this murine model of HHT, it appears that epigenetic factors and modifier genes, some of which are present in 129/Ola, contribute to disease heterogeneity.
Annual Report to the Nation on the Status of Cancer, 1973-1996, With a Special Section on Lung Cancer and Tobacco Smoking
Authors: P A Wingo, L A Ries, G A Giovino, D S Miller, H M Rosenberg, D R Shopland, M J Thun, B K Edwards
Journal: JNCI Journal of the National Cancer Institute (1999)

The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS), provide the second annual report to the nation on progress in cancer prevention and control, with a special section on lung cancer and tobacco smoking.Age-adjusted rates (using the 1970 U.S. standard population) were based on cancer incidence data from NCI and underlying cause of death data compiled by NCHS. The prevalence of tobacco use was derived from CDC surveys. Reported P values are two-sided.From 1990 through 1996, cancer incidence (-0.9% per year; P = .16) and cancer death (-0.6% per year; P = .001) rates for all sites combined decreased. Among the 10 leading cancer incidence sites, statistically significant decreases in incidence rates were seen in males for leukemia and cancers of the lung, colon/rectum, urinary bladder, and oral cavity and pharynx. Except for lung cancer, incidence rates for these cancers also declined in females. Among the 10 leading cancer mortality sites, statistically significant decreases in cancer death rates were seen for cancers of the male lung, female breast, the prostate, male pancreas, and male brain and, for both sexes, cancers of the colon/rectum and stomach. Age-specific analyses of lung cancer revealed that rates in males first declined at younger ages and then for each older age group successively over time; rates in females appeared to be in the early stages of following the same pattern, with rates decreasing for women aged 40-59 years.The declines in cancer incidence and death rates, particularly for lung cancer, are encouraging. However, unless recent upward trends in smoking among adolescents can be reversed, the lung cancer rates that are currently declining in the United States may rise again.
Risk of Death in Elderly Users of Conventional vs. Atypical Antipsychotic Medications
Authors: Philip S. Wang, Sebastian Schneeweiss, Jerry Avorn, Michael A. Fischer, Helen Mogun, Daniel H. Solomon, M. Alan Brookhart
Journal: New England Journal of Medicine (2005)

Recently, the Food and Drug Administration (FDA) issued an advisory stating that atypical antipsychotic medications increase mortality among elderly patients. However, the advisory did not apply to conventional antipsychotic medications; the risk of death with these older agents is not known.We conducted a retrospective cohort study involving 22,890 patients 65 years of age or older who had drug insurance benefits in Pennsylvania and who began receiving a conventional or atypical antipsychotic medication between 1994 and 2003. Analyses of mortality rates and Cox proportional-hazards models were used to compare the risk of death within 180 days, less than 40 days, 40 to 79 days, and 80 to 180 days after the initiation of therapy with an antipsychotic medication. We controlled for potential confounding variables with the use of traditional multivariate Cox models, propensity-score adjustments, and an instrumental-variable analysis.Conventional antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (< or =180 days: relative risk, 1.37; 95 percent confidence interval, 1.27 to 1.49; <40 days: relative risk, 1.56; 95 percent confidence interval, 1.37 to 1.78; 40 to 79 days: relative risk, 1.37; 95 percent confidence interval, 1.19 to 1.59; and 80 to 180 days: relative risk, 1.27; 95 percent confidence interval, 1.14 to 1.41) and in all subgroups defined according to the presence or absence of dementia or nursing home residency. The greatest increases in risk occurred soon after therapy was initiated and with higher dosages of conventional antipsychotic medications. Increased risks associated with conventional as compared with atypical antipsychotic medications persisted in confirmatory analyses performed with the use of propensity-score adjustment and instrumental-variable estimation.If confirmed, these results suggest that conventional antipsychotic medications are at least as likely as atypical agents to increase the risk of death among elderly persons and that conventional drugs should not be used to replace atypical agents discontinued in response to the FDA warning.
The Social Environment and Health: A Discussion of the Epidemiologic Literature
Authors: I. H. Yen, S. Leonard Syme
Journal: Annual Review of Public Health (1999)

▪ Abstract The environment can be thought of in terms of physical and social dimensions. The social environment includes the groups to which we belong, the neighborhoods in which we live, the organization of our workplaces, and the policies we create to order our lives. There have been recent reports in the literature that the social environment is associated with disease and mortality risks, independent of individual risk factors. These findings suggest that the social environment influences disease pathways. Yet much remains to be learned about the social environment, including how to understand, define, and measure it. The research that needs to be done could benefit from a long tradition in sociology and sociological research that has examined the urban environment, social areas, social disorganization, and social control. We summarize this sociological literature and discuss its relevance to epidemiologic research.
GABA<sub>A</sub>Receptor-Modulating Neuroactive Steroid Composition in Patients With Panic Disorder Before and During Paroxetine Treatment
Authors: Andreas Ströhle, Elena Romeo, Flavia di Michele, Augusto Pasini, Alexander Yassouridis, Florian Holsboer, Rainer Rupprecht
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Previous studies have shown that neuroactive steroids modulate anxiety and stress reactivity. However, no data on the possible role of these γ-aminobutyric acidA (GABAA) receptor-modulating neuroactive steroids in patients with anxiety disorders are available. METHOD: The concentrations of 3α,5α-tetrahydroprogesterone (3α,5α-THP), 3α,5β-THP, 3β,5α-THP, and their precursors were studied in the plasma of 10 patients with panic disorder and 10 matched healthy comparison subjects. In addition, the effects of paroxetine treatment on neuroactive steroid concentrations were studied in the panic disorder patients over a 24-week period. RESULTS: Unexpectedly, patients with panic disorder had significantly greater concentrations of the positive allosteric modulators 3α,5α-THP and 3α,5β-THP and significantly lower concentrations of 3β,5α-THP (a functional antagonist for GABAA agonistic steroids), which might result in greater GABAA receptor-mediated neuronal activity. Paroxetine treatment did not affect neuroactive steroid concentrations, which were highly stable over 24 weeks. CONCLUSIONS: Differences in neuroactive steroid composition in patients with panic disorder were the opposite of those seen in patients with major depression and may reflect counterregulative mechanisms against the occurrence of spontaneous panic attacks.
Cardiac sodium and calcium channels: a history of excitatory currents
Authors: H Fozzard
Journal: Cardiovascular Research (2002)

The entire concept of ion channels as molecular machines to gate ion traffic across the membrane has only recently been generally recognized, even though ion channels are found in almost all cells. Na+ and Ca2+ channels are the basis of excitability, and in the heart they generate the rhythm, coordinating and controling cardiac contraction. Dysfunction of ion channels results in arrhythmias that underlie 20–25% of deaths in the developed world, and some arrhythmias result directly from gene defects in ion channels. This is my personal perspective on the critical ideas and the pioneers in the field of cardiac Na+ and Ca2+ channels.