tbuckley/cabot-search huggingface dataset:
Excess Risk of Chronic Kidney Disease among African-American versus White Subjects in the United States
Authors: Michelle E. Tarver-Carr, Neil R. Powe, Mark S. Eberhardt, Thomas A. LaVeist, Raynard S. Kington, Josef Coresh, Frederick L. Brancati
Journal: Journal of the American Society of Nephrology (2002)

African Americans experience higher rates of chronic kidney disease (CKD) than do whites. It was hypothesized that racial differences in modifiable factors would account for much of the excess risk of CKD. A cohort study of 9082 African-American and white adults of age 30 to 74 yr, who participated in the Second National Health and Nutrition Examination Survey in 1976 to 1980 and were monitored for vital status through 1992 in the Second National Health and Nutrition Examination Survey Mortality Study, was conducted. Incident CKD was defined as treated CKD cases (ascertained by linkage to the Medicare Registry) and deaths related to kidney disease. The incidence of all-cause CKD was 2.7 times higher among African Americans, compared with whites. Adjustment for sociodemographic factors decreased the relative risk (RR) to 2.49, explaining 12% of the excess risk of CKD among African Americans. Further adjustment for lifestyle factors explained 24% of the excess risk, whereas adjustment for clinical factors alone explained 32%. Simultaneous adjustment for sociodemographic, lifestyle, and clinical factors attenuated the RR to 1.95 (95% confidence interval, 1.05 to 3.63), explaining 44% of the excess risk. Although the excess risk of CKD among African Americans was much greater among middle-age adults (30 to 59 yr of age; RR = 4.23, statistically significant) than among older adults (60 to 74 yr of age; RR = 1.27), indicating an interaction between race and age, the same patterns of explanatory factors were observed for the two age groups. Nearly one-half of the excess risk of CKD among African-American adults can be explained on the basis of potentially modifiable risk factors; however, much of the excess risk remains unexplained.
Preclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis
Authors: Mary J. Roman, Elfi Moeller, Adrienne Davis, Stephen A. Paget, Mary K. Crow, Michael D. Lockshin, Lisa Sammaritano, Richard B. Devereux, Joseph E. Schwartz, Daniel M. Levine, Jane E. Salmon
Journal: Annals of Internal Medicine (2006)

Background: Rheumatoid arthritis is associated with increased morbidity and mortality because of cardiovascular disease, independent of traditional risk factors. Objective: To determine the prevalence of preclinical atherosclerosis in patients with rheumatoid arthritis and to identify clinical and biological markers for atherosclerotic disease in this patient population. Design: Matched, cross-sectional study. Setting: Hospital for Special Surgery in New York City. Patients: 98 consecutive outpatients with rheumatoid arthritis who were followed by rheumatologists and 98 controls matched on age, sex, and ethnicity. Measurements: Cardiovascular risk factor ascertainment and carotid ultrasonography in all participants; disease severity, disease treatment, and inflammatory markers in patients with rheumatoid arthritis. Results: Despite a more favorable risk factor profile, patients with rheumatoid arthritis had a 3-fold increase in carotid atherosclerotic plaque (44% vs. 15%; P < 0.001). The relationship between rheumatoid arthritis and carotid atherosclerotic plaque remained after accounting for age, serum cholesterol levels, smoking history, and hypertensive status; adjusted predicted prevalence was 7.4% (95% CI, 3.4% to 15.2%) for the control group and 38.5% (CI, 25.4% to 53.5%) for patients with rheumatoid arthritis. Age (P < 0.001) and current cigarette use (P < 0.014) were also significantly associated with carotid atherosclerotic plaque. Among patients with rheumatoid arthritis, atherosclerosis was related to age, hypertension status, and use of tumor necrosis factor-α inhibitors (a possible marker of disease severity). Limitations: The study had a cross-sectional design, and inflammatory markers were determined only once. Conclusions: Patients with rheumatoid arthritis have a high prevalence of preclinical atherosclerosis independent of traditional risk factors, suggesting that chronic inflammation and, possibly, disease severity are atherogenic in this population.
miR-148a plays a pivotal role in the liver by promoting the hepatospecific phenotype and suppressing the invasiveness of transformed cells
Authors: Luc Gailhouste, Laura Gomez-Santos, Keitaro Hagiwara, Izuho Hatada, Noriyuki Kitagawa, Kazushi Kawaharada, Muriel Thirion, Nobuyoshi Kosaka, Ryou-u Takahashi, Tatsuhiro Shibata, Atsushi Miyajima, Takahiro Ochiya
Journal: Hepatology (2013)

MicroRNAs (miRNAs) are evolutionary conserved small RNAs that post-transcriptionally regulate the expression of target genes. To date, the role of miRNAs in liver development is not fully understood. By using an experimental model that allows the induced and controlled differentiation of mouse fetal hepatoblasts (MFHs) into mature hepatocytes, we identified miR-148a as a hepatospecific miRNA highly expressed in adult liver. The main finding of this study revealed that miR-148a was critical for hepatic differentiation through the direct targeting of DNA methyltransferase (DNMT) 1, a major enzyme responsible for epigenetic silencing, thereby allowing the promotion of the "adult liver" phenotype. It was also confirmed that the reduction of DNMT1 by RNA interference significantly promoted the expression of the major hepatic biomarkers. In addition to the essential role of miR-148a in hepatocyte maturation, we identified its beneficial effect through the repression of hepatocellular carcinoma (HCC) cell malignancy. miR-148a expression was frequently down-regulated in biopsies of HCC patients as well as in mouse and human HCC cell lines. Overexpressing miR-148a led to an enhancement of albumin production and a drastic inhibition of the invasive properties of HCC cells, whereas miR-148a silencing had the opposite consequences. Finally, we showed that miR-148a exerted its tumor-suppressive effect by regulating the c-Met oncogene, regardless of the DNMT1 expression level.miR-148a is essential for the physiology of the liver because it promotes the hepatospecific phenotype and acts as a tumor suppressor. Most important, this report is the first to demonstrate a functional role for a specific miRNA in liver development through regulation of the DNMT1 enzyme.
General Practice Observed: The Distress of Dying
Authors: W. D. Rees
Journal: BMJ (1972)

A simple method of recording the distress of dying patients is described. Significant differences occurred between deaths at home and in hospital for three factors. Patients dying at home were (a) more likely to be fully alert shortly before death (P < 0.05); (b) less likely to be suffering from vomiting, incontinence, or bedsores (P < 0.001); and (c) less likely to have unrelieved physical distress (P < 0.05). No significant differences occurred in the distress of patients dying in general-practitioner compared with other hospitals, though the numbers compared were small and a larger study might prove useful.
Pathogenic CD4+ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes
Authors: James F. Mohan, Boris Calderon, Mark S. Anderson, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2013)

In the nonobese diabetic mouse, a predominant component of the autoreactive CD4+ T cell repertoire is directed against the B:9-23 segment of the insulin B chain. Previous studies established that the majority of insulin-reactive T cells specifically recognize a weak peptide-MHC binding register within the B:9-23 segment, that to the 12–20 register. These T cells are uniquely stimulated when the B:9-23 peptide, but not the insulin protein, is offered to antigen presenting cells (APCs). Here, we report on a T cell receptor (TCR) transgenic mouse (8F10) that offers important new insights into the biology of these unconventional T cells. Many of the 8F10 CD4+ T cells escaped negative selection and were highly pathogenic. The T cells were directly recruited into islets of Langerhans, where they established contact with resident intra-islet APCs. Immunogenic insulin had to be presented in order for the T cells to localize and cause disease. These T cells bypassed an initial priming stage in the pancreatic lymph node thought to precede islet T cell entry. 8F10 T cells induced the production of antiinsulin antibodies and islets contained immunoglobulin (IgG) deposited on β cells and along the vessel walls.
Medication Adherence
Authors: P. Michael Ho, Chris L. Bryson, John S. Rumsfeld
Journal: Circulation (2009)

Medication adherence usually refers to whether patients take their medications as prescribed (eg, twice daily), as well as whether they continue to take a prescribed medication. Medication nonadherence is a growing concern to clinicians, healthcare systems, and other stakeholders (eg, payers) because of mounting evidence that it is prevalent and associated with adverse outcomes and higher costs of care. To date, measurement of patient medication adherence and use of interventions to improve adherence are rare in routine clinical practice. The goals of the present report are to address (1) different methods of measuring adherence, (2) the prevalence of medication nonadherence, (3) the association between nonadherence and outcomes, (4) the reasons for nonadherence, and finally, (5) interventions to improve medication adherence.
EYA1 Phosphatase Function Is Essential to Drive Breast Cancer Cell Proliferation through Cyclin D1
Authors: Kongming Wu, Zhaoming Li, Shaoxin Cai, Lifeng Tian, Ke Chen, Jing Wang, Junbo Hu, Ye Sun, Xue Li, Adam Ertel, Richard G. Pestell
Journal: Cancer Research (2013)

Abstract The Drosophila Eyes Absent Homologue 1 (EYA1) is a component of the retinal determination gene network and serves as an H2AX phosphatase. The cyclin D1 gene encodes the regulatory subunits of a holoenzyme that phosphorylates and inactivates the pRb protein. Herein, comparison with normal breast showed that EYA1 is overexpressed with cyclin D1 in luminal B breast cancer subtype. EYA1 enhanced breast tumor growth in mice in vivo, requiring the phosphatase domain. EYA1 enhanced cellular proliferation, inhibited apoptosis, and induced contact-independent growth and cyclin D1 abundance. The induction of cellular proliferation and cyclin D1 abundance, but not apoptosis, was dependent upon the EYA1 phosphatase domain. The EYA1-mediated transcriptional induction of cyclin D1 occurred via the AP-1–binding site at −953 and required the EYA1 phosphatase function. The AP-1 mutation did not affect SIX1-dependent activation of cyclin D1. EYA1 was recruited in the context of local chromatin to the cyclin D1 AP-1 site. The EYA1 phosphatase function determined the recruitment of CBP, RNA polymerase II, and acetylation of H3K9 at the cyclin D1 gene AP-1 site regulatory region in the context of local chromatin. The EYA1 phosphatase regulates cell-cycle control via transcriptional complex formation at the cyclin D1 promoter. Cancer Res; 73(14); 4488–99. ©2013 AACR.
Measuring Abdominal Obesity: Effects of Height on Distribution of Cardiometabolic Risk Factors Risk Using Waist Circumference and Waist-to-Height Ratio
Authors: Harald J. Schneider, Jens Klotsche, Sigmund Silber, Günter K. Stalla, Hans-Ulrich Wittchen
Journal: Diabetes Care (2010)

Accumulating evidence suggests that measures of abdominal obesity outperform BMI in predicting diabetes and cardiovascular risk (1-3).However, it is debated which measure of obesity should be used.Currently, waist circumference (WC) is most commonly used and codefines the metabolic syndrome (4).Unlike waist-to-height ratio (WHtR), WC does not take differences in height into account.We hypothesized that short subjects with a WC at a specified cutoff-point will have more abdominal fat and associated cardiovascular risk factors than tall subjects with a WC at the same cutoff-point and that this will not be the case if WHtR is used instead of WC.To test this hypothesis, we compared the distribution of cardiovascular risk factors according to height above and below commonly used cutoffs of WC and WHtR in a cross-sectional study.It is unlikely that our findings can be attributed to height itself because differences in the expected directions were only present if individuals were grouped by WC and not by WHtR.WHtR is simple to assess.Therefore, we suggest that WHtR instead of WC should be implemented in obesity guidelines and in the definition of the metabolic syndrome.
Pathologic Complete Response With Six Compared With Three Cycles of Neoadjuvant Epirubicin Plus Docetaxel and Granulocyte Colony-Stimulating Factor in Operable Breast Cancer: Results of ABCSG-14
Authors: Günther G. Steger, Arik Galid, Michael Gnant, Brigitte Mlineritsch, Alois Lang, Christoph Tausch, Margaretha Rudas, Richard Greil, Catharina Wenzel, Christian F. Singer, Anton Haid, Sabine Pöstlberger, Hellmut Samonigg, Gero Luschin-Ebengreuth, Werner Kwasny, Eduard Klug, Ernst Kubista, Christian Menzel, Raimund Jakesz
Journal: Journal of Clinical Oncology (2007)

Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate.Patients with biopsy-proven breast cancer (T1-4a-c, N+/-, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery.A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment.Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.
Phase II Study of the Mitogen-Activated Protein Kinase 1/2 Inhibitor Selumetinib in Patients With Advanced Hepatocellular Carcinoma
Authors: Bert H. O'Neil, Laura W. Goff, John Sae Wook Kauh, Jonathan R. Strosberg, Tanios S. Bekaii-Saab, Ruey-min Lee, Aslamuzzaman Kazi, Dominic T. Moore, Maria Learoyd, Richard M. Lush, Said M. Sebti, Daniel M. Sullivan
Journal: Journal of Clinical Oncology (2011)

PURPOSE Hepatocellular carcinoma (HCC) is a common and deadly malignancy with few systemic therapy options. The RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is activated in approximately 50% to 60% of HCCs and represents a potential target for therapy. Selumetinib is an orally available inhibitor of MEK tyrosine kinase activity. PATIENTS AND METHODS Patients with locally advanced or metastatic HCC who had not been treated with prior systemic therapy were enrolled on to the study. Patients were treated with selumetinib at its recommended phase II dose of 100 mg twice per day continuously. Cycle length was 21 days. Imaging was performed every two cycles. Biopsies were obtained at baseline and at steady-state in a subset of patients, and pharmacokinetic (PK) analysis was performed on all patients. Results Nineteen patients were enrolled, 17 of whom were evaluable for response. Most (82%) had Child-Pugh A cirrhosis. Toxicity was in line with other studies of selumetinib in noncirrhotic patients. PK parameters were also comparable to those in noncirrhotic patients. No radiographic response was observed in this group, and the study was stopped at the interim analysis. Of 11 patients with elevated α-fetoprotein, three (27%) had decreases of 50% or more. Median time to progression was 8 weeks. Inhibition of ERK phosphorylation was demonstrated by Western blotting. CONCLUSION In this study of selumetinib for patients with HCC, no radiographic responses were seen and time to progression was short, which suggests minimal single-agent activity despite evidence of suppression of target activation.
T-Wave Alternans in the Sudden Cardiac Death in Heart Failure Trial Population
Authors: David S. Rosenbaum
Journal: Circulation (2008)

A lthough the cardiovascular death rate has fallen in recent years, the proportion of cardiovascular deaths attributed to sudden cardiac death (SCD) is on the rise.SCD is usually caused by ventricular tachyarrhythmias resulting from complex electroanatomic changes that follow myocardial injury, most often associated with coronary artery disease.Ventricular tachyarrhythmia episodes and the factors responsible for triggering them are poorly understood, usually occur without warning or provocation, and result almost invariably in death.Therefore, efforts aimed at predicting and preventing SCD have emerged as the major paradigm for addressing this significant unresolved public health dilemma.
Urticaria from allergy to a purified human anti-Rh antibody preparation
Authors: I. Sulakvelidze, S. Evans, I. Switzer, B. Underdown, J. Greenbaum, J. Dolovich
Journal: Allergy (1995)

This case presentation describes a young woman who developed generalized urticaria after receiving the human anti-RhD(D) preparation, WinRho, intravenously. Allergy skin tests and the radioallergosorbent test (RAST) for IgE antibodies to the human anti-D immunoglobulin preparation were positive. Further studies using high-pressure liquid chromatography and protein A column chromatography implicated a nonimmunoglobulin low-molecular-weight contaminant. This case report illustrates an allergic reaction to a highly purified human immunoglobulin preparation, and demonstrates approaches to assessment of such a reaction.
Notch1-Induced Transformation of RKE-1 Cells Requires Up-regulation of Cyclin D1
Authors: Mark Stahl, Changhui Ge, Shaolin Shi, Richard G. Pestell, Pamela Stanley
Journal: Cancer Research (2006)

RKE-1 cells induced to overexpress activated Notch1 (RKE-ER-N(ic)) exhibit increased cyclin D1 transcripts and become transformed. However, the oncogenic pathway of Notch1-induced transformation is not known. Here, we use mutational analysis to functionally identify the sole region of the cyclin D1 promoter that responds to activated Notch1. The same region responds to activated Notch4 as well as to physiologic Notch ligand-induced Notch receptor signaling. The cyclin D1 gene was subsequently found to be a physiologic target of Notch signaling in Pofut1(-/-) mouse embryos defective in canonical Notch signaling and in embryos with an inactivating mutation in Notch1. To determine if Notch1-induced cyclin D1 expression in RKE-ER-N(ic) cells plays a direct role in transformation, cyclin D1 up-regulation was inhibited using a cyclin D1 antisense cDNA. We report here that transformation of RKE-ER-N(ic) cells is dependent on increased expression of cyclin D1 protein, which represents a new mechanism of Notch1-induced transformation.
Automated DNA Sequence-Based Early Warning System for the Detection of Methicillin-Resistant Staphylococcus aureus Outbreaks
Authors: Alexander Mellmann, Alexander W Friedrich, Nicole Rosenkötter, Jörg Rothgänger, Helge Karch, Ralf Reintjes, Dag Harmsen
Journal: PLoS Medicine (2006)

Background The detection of methicillin-resistant Staphylococcus aureus (MRSA) usually requires the implementation of often rigorous infection-control measures. Prompt identification of an MRSA epidemic is crucial for the control of an outbreak. In this study we evaluated various early warning algorithms for the detection of an MRSA cluster. Methods and Findings Between 1998 and 2003, 557 non-replicate MRSA strains were collected from staff and patients admitted to a German tertiary-care university hospital. The repeat region of the S. aureus protein A (spa) gene in each of these strains was sequenced. Using epidemiological and typing information for the period 1998–2002 as reference data, clusters in 2003 were determined by temporal-scan test statistics. Various early warning algorithms (frequency, clonal, and infection control professionals [ICP] alerts) were tested in a prospective analysis for the year 2003. In addition, a newly implemented automated clonal alert system of the Ridom StaphType software was evaluated. A total of 549 of 557 MRSA were typeable using spa sequencing. When analyzed using scan test statistics, 42 out of 175 MRSA in 2003 formed 13 significant clusters (p < 0.05). These clusters were used as the "gold standard" to evaluate the various algorithms. Clonal alerts (spa typing and epidemiological data) were 100% sensitive and 95.2% specific. Frequency (epidemiological data only) and ICP alerts were 100% and 62.1% sensitive and 47.2% and 97.3% specific, respectively. The difference in specificity between clonal and ICP alerts was not significant. Both methods exhibited a positive predictive value above 80%. Conclusions Rapid MRSA outbreak detection, based on epidemiological and spa typing data, is a suitable alternative for classical approaches and can assist in the identification of potential sources of infection.
Health disparities in arthritis and musculoskeletal and skin diseases—the dermatology session: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, December 15-16, 2000
Authors: Susan C. Taylor, A.Paul Kelly, Natalie E. Dupree, Alexa Boer Kimball, Reva C. Lawrence
Journal: Journal of the American Academy of Dermatology (2002)
Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla
Authors: C Gregory Elliott
Journal: New England Journal of Medicine (2014)

According to Homer, Odysseus was forced to choose whether to steer his ship closer to Scylla, a six-headed sea monster, or Charybdis, a ship-swallowing whirlpool. Odysseus steered closer to Scylla, risking the loss of a few sailors, rather than risking an entire ship and crew.Much like Odysseus, the physician treating a patient with acute pulmonary embolism occasionally must navigate treacherous waters. The risk of fatal thromboembolism stands on one side, and the risk of fatal bleeding lies just opposite. Unlike Odysseus, the physician has empirical evidence to guide decisions, but tragic outcomes occur sometimes, no matter how carefully the . . .