tbuckley/cabot-search huggingface dataset:
Objectively Measured Sedentary Time and Cardiometabolic Biomarkers in US Hispanic/Latino Adults
Authors: Qibin Qi, Garrett Strizich, Gina Merchant, Daniela Sotres-Alvarez, Christina Buelna, Sheila F. Castañeda, Linda C. Gallo, Jianwen Cai, Marc D. Gellman, Carmen R. Isasi, Ashley E. Moncrieft, Lisa Sanchez-Johnsen, Neil Schneiderman, Robert C. Kaplan
Journal: Circulation (2015)

Background— Sedentary behavior is recognized as a distinct construct from lack of moderate-vigorous physical activity and is associated with deleterious health outcomes. Previous studies have primarily relied on self-reported data, whereas data on the relationship between objectively measured sedentary time and cardiometabolic biomarkers are sparse, especially among US Hispanics/Latinos. Methods and Results— We examined associations of objectively measured sedentary time (via Actical accelerometers for 7 days) and multiple cardiometabolic biomarkers among 12 083 participants, aged 18 to 74 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos of diverse backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) were recruited from 4 US cities between 2008 and 2011. Sedentary time (&lt;100 counts/min) was standardized to 16 hours/d of wear time. The mean sedentary time was 11.9 hours/d (74% of accelerometer wear time). After adjustment for moderate-vigorous physical activity and confounding variables, prolonged sedentary time was associated with decreased high-density lipoprotein cholesterol ( P =0.04), and increased triglycerides, 2-hour glucose, fasting insulin, and homeostatic model assessment of insulin resistance (all P &lt;0.0001). These associations were generally consistent across age, sex, Hispanic/Latino backgrounds, and physical activity levels. Even among individuals meeting physical activity guidelines, sedentary time was detrimentally associated with several cardiometabolic biomarkers (diastolic blood pressure, high-density lipoprotein cholesterol, fasting and 2-hour glucose, fasting insulin and homeostatic model assessment of insulin resistance; all P &lt;0.05). Conclusions— Our large population-based, objectively derived data showed deleterious associations between sedentary time and cardiometabolic biomarkers, independent of physical activity, in US Hispanics/Latinos. Our findings emphasize the importance of reducing sedentary behavior for the prevention of cardiometabolic diseases, even in those who meet physical activity recommendations.
Prompting Physicians to Address a Daily Checklist and Process of Care and Clinical Outcomes
Authors: Curtis H. Weiss, Farzad Moazed, Colleen A. McEvoy, Benjamin D. Singer, Igal Szleifer, Luís A. N. Amaral, Mary Kwasny, Charles M. Watts, Stephen D. Persell, David W. Baker, Jacob I. Sznajder, Richard G. Wunderink
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Checklists may reduce errors of omission for critically ill patients.To determine whether prompting to use a checklist improves process of care and clinical outcomes.We conducted a cohort study in the medical intensive care unit (MICU) of a tertiary care university hospital. Patients admitted to either of two independent MICU teams were included. Intervention team physicians were prompted to address six parameters from a daily rounding checklist if overlooked during morning work rounds. The second team (control) used the identical checklist without prompting.One hundred and forty prompted group patients were compared with 125 control and 1,283 preintervention patients. Compared with control, prompting increased median ventilator-free duration, decreased empirical antibiotic and central venous catheter duration, and increased rates of deep vein thrombosis and stress ulcer prophylaxis. Prompted group patients had lower risk-adjusted ICU mortality compared with the control group (odds ratio, 0.36; 95% confidence interval, 0.13-0.96; P = 0.041) and lower hospital mortality compared with the control group (10.0 vs. 20.8%; P = 0.014), which remained significant after risk adjustment (odds ratio, 0.34; 95% confidence interval, 0.15-0.76; P = 0.008). Observed-to-predicted ICU length of stay was lower in the prompted group compared with control (0.59 vs. 0.87; P = 0.02). Checklist availability alone did not improve mortality or length of stay compared with preintervention patients.In this single-site, preliminary study, checklist-based prompting improved multiple processes of care, and may have improved mortality and length of stay, compared with a stand-alone checklist. The manner in which checklists are implemented is of great consequence in the care of critically ill patients.
Extracranial Oligometastases: A Subset of Metastases Curable With Stereotactic Radiotherapy
Authors: Kimberly S. Corbin, Samuel Hellman, Ralph R. Weichselbaum
Journal: Journal of Clinical Oncology (2013)

The term oligometastases, introduced in 1995 and detailed more recently, describes an intermediate state of cancer spread between localized disease and widespread metastases. Metastases from solid tumors are regarded as representative of disseminated cancer and are not considered curable, with the rare exception, such as germ cell tumors. By contrast, evidence has emerged that patients with limited metastatic disease, such as liver metastasis from colon or rectal cancer, can be cured by removal of the metastasis, drawing increased focus on the potential for intermediate states of metastatic cancer involvement. The implication of the concept of an oligometastatic state is that metastatic disease may be cured with metastasis-directed therapy. As a further conceptual refinement, Niibe et al have suggested the concept of oligorecurrence to consider patients with a limited number of metastases and controlled primary tumors as a group with an improved prognosis as compared with patients with limited metastasis and uncontrolled primary tumors. The oligometastatic hypothesis is distinct from other potentially important uses of radiotherapy and surgery in metastatic disease, such as consolidation of chemotherapy responses or as an application of the Norton-Simon hypothesis, which predicts that effectiveness of chemotherapy is proportional to the growth rate of the tumor and that the fastest growth rates occur in nonbulky tumors. Aggressive local therapy to metastatic lesions can downsize tumors, and the remaining cells might therefore be more sensitive to chemotherapy. Our review will focus on extracranial oligometastases because intracranial oligometastasis is an established clinical entity where surgery, radiotherapy, and radiosurgery have defined roles supported by phase III randomized trials and detailed outcome analyses.
Mechanisms of Inactivation of <i>PTCH1</i> Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis
Authors: Shuang Pan, Qing Dong, Li-Sha Sun, Tie-Jun Li
Journal: Clinical Cancer Research (2010)

PTCH1 has been identified as the gene responsible for nevoid basal cell carcinoma syndrome (NBCCS). Keratocystic odontogenic tumors (KCOT) are aggressive jaw lesions that may occur in isolation or in association with NBCCS. The aim of this study was to investigate the genetic and/or epigenetic mechanisms of inactivation of the PTCH1 gene in patients with NBCCS and related sporadic KCOTs.Loss of heterozygosity was analyzed in 44 patients (15 NBCCS-related and 29 sporadic KCOTs), all of whom were previously analyzed for PTCH1 mutations. Allelic location was established in tumors carrying two coincident mutations. PTCH1 mRNA expression and promoter methylation status were analyzed in a panel of KCOTs to define the possible role of epigenetic effects on PTCH1 inactivation.Although mutations and loss of heterozygosity of PTCH1 were frequently detected in both syndromic and nonsyndromic cases, hypermethylation of the PTCH1 promoter was not identified in the present series. Of all the 44 cases examined, 13 were identified to fit the two-hit model, 14 to conform to a one-hit model, and the remaining 17 cases showing no alteration in PTCH1. The distribution of two-hit, one-hit, and non-hit cases was significantly different between syndrome and nonsyndrome patients (P < 0.02).This study indicates that PTCH1 gene alternation may play a significant role in the pathogenesis of NBCCS and the related sporadic tumors. Not only the standard two-hit model, but also haploinsufficiency or dominant-negative isoforms may be implicated in the inactivation of the PTCH1 gene.
Antihypertensive Effect of Hypophysectomy in Dogs with Hypertension Following Bilateral Carotid Sinus Constriction
Authors: EDWARD W. HAWTHORNE, MARY GASPAR
Journal: Circulation Research (1959)

A chronic type of experimental hypertension has been produced in dogs by bilateral sinus area constriction. Hypophysectomy has a prolonged antihypertensive effect in dogs with persistent hypertension resulting from carotid sinus area constriction, while no decrease in mean arterial pressure is seen after hypophysectomy in normotensive control dogs. These findings suggest the possibility that altered hypophyseal function participates in the pathogenesis of this type of hypertension.
Cardiovascular complications of outpatient cardiac rehabilitation programs
Authors: S. P. Van Camp
Journal: JAMA (1986)

To determine the incidence of major cardiovascular complications in outpatient cardiac rehabilitation programs, we obtained data from 167 randomly selected cardiac rehabilitation programs via mailed questionnaires and follow-up telephone calls. These 167 programs reported that 51 303 patients exercised 2 351 916 hours from January 1980 through December 1984. Twenty-one cardiac arrests (18 in which the patient was successfully resuscitated and three fatal) and eight nonfatal myocardial infarctions were reported. The incidence rates per million patient hours of exercise were 8.9 for cardiac arrests (one per 111 996 patient-hours), 3.4 for myocardial infarctions (one per 293 990 patient-hours), and 1.3 for fatalities (one per 783 972 patient-hours). There was no statistically significant difference in frequency of these events among programs of varying size or extent of electrocardiographic monitoring. These data indicate that current cardiac rehabilitation practice allows for prescribed supervised exercise by patients with cardiovascular disease to be performed at a low risk of major cardiovascular complications. (<i>JAMA</i>1986;256:1160-1163)
Prevalence Of Sleep Disorders In Children With Asthma and Its Association With The Level Of Control Of The Disease, Smoking and Obesity
Authors: Lorena Rangel-Garza, Sandra N. Gonzalez-Diaz, Alejandra Macias-Weinmann, Alfredo Arias-Cruz, Maria Del Carmen Zarate-Hernandez, Idalia V. Yanez-Perez, Hilda Hernandez-Sanchez
Journal: Journal of Allergy and Clinical Immunology (2014)
Busulfan in Infant to Adult Hematopoietic Cell Transplant Recipients: A Population Pharmacokinetic Model for Initial and Bayesian Dose Personalization
Authors: Jeannine S. McCune, Meagan J. Bemer, Jeffrey S. Barrett, K. Scott Baker, Alan S. Gamis, Nicholas H.G. Holford
Journal: Clinical Cancer Research (2013)

Personalizing intravenous busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict i.v. busulfan doses over a wide age spectrum (0.1-66 years) that accounts for differences in age and body size.A population pharmacokinetic model based on normal fat mass and maturation based on postmenstrual age was built from 12,380 busulfan concentration time points obtained after i.v. busulfan administration in 1,610 HCT recipients. Subsequently, simulation results of the initial dose necessary to achieve a target Css with this model were compared with pediatric-only models.A two-compartment model with first-order elimination best fit the data. The population busulfan clearance was 12.4 L/h for an adult male with 62 kg normal fat mass (equivalent to 70 kg total body weight). Busulfan clearance, scaled to body size-specifically normal fat mass, is predicted to be 95% of the adult clearance at 2.5 years postnatal age. With a target Css of 770 ng/mL, a higher proportion of initial doses achieved the therapeutic window with this age- and size--dependent model (72%) compared with dosing recommended by the U.S. Food and Drug Administration (57%) or the European Medicines Agency (70%).This is the first population pharmacokinetic model developed to predict initial i.v. busulfan doses and personalize to a target Css over a wide age spectrum, ranging from infants to adults.
Differential effects of elevating [K]o on three transient outward potassium channels. Dependence on channel inactivation mechanisms.
Authors: G N Tseng, J Tseng-Crank
Journal: Circulation Research (1992)

We carried out a systematic study on the effects of elevating [K]o on the properties of a transient outward potassium channel encoded by a cardiac cDNA (RHK1) and compared them with those on two Shaker potassium channels (H-4 and H-37). The amino acid sequences of all three channels are known, and their structure-function relations have been partially characterized. All three channels were expressed in Xenopus oocytes and studied under double-microelectrode voltage-clamp conditions. For all three channels, elevating [K]o caused an increase in the channels' chord conductances and a negative shift in the calculated activation curves. However, in other aspects of channel properties that are related to the channels' inactivation processes, there were differences in the changes induced by increasing [K]o: 1) Elevating [K]o caused a positive shift in the steady-state inactivation curves of RHK1 and H-4 but did not cause any shift in H-37. 2) Elevating [K]o slowed the time course of inactivation of H-37 but did not cause any significant changes in the time course of RHK1 or H-4. 3) Elevating [K]o accelerated the rate of recovery from inactivation of RHK1 and H-4 but slowed the recovery time course of H-37. Our experiments show that elevating [K]o can cause a wide range of effects on the transient outward potassium channels. Furthermore, raising [K]o induced similar changes in RHK1 and H-4 (inactivation mediated by an "N-type" mechanism) that were different from the changes in H-37 (inactivation mediated by a "C-type" mechanism). Therefore, our data suggest that part of the effects of elevating [K]o on channel properties may depend on the channel's inactivation mechanism. This hypothesis is supported by results from experiments studying the effects of elevating [K]o on a mutant RHK1 channel (RHK1 delta 3-25), which apparently lacks the N-type and C-type inactivation mechanisms.
CXCL13 is an arrest chemokine for B cells in high endothelial venules
Authors: Naotoshi Kanemitsu, Yukihiko Ebisuno, Toshiyuki Tanaka, Kazuhiro Otani, Haruko Hayasaka, Tsuneyasu Kaisho, Shizuo Akira, Koko Katagiri, Tatsuo Kinashi, Naoya Fujita, Takashi Tsuruo, Masayuki Miyasaka
Journal: Blood (2005)
ASC-J9 Suppresses Renal Cell Carcinoma Progression by Targeting an Androgen Receptor–Dependent HIF2α/VEGF Signaling Pathway
Authors: Dalin He, Lei Li, Guodong Zhu, Liang Liang, Zhenfeng Guan, Luke Chang, Yuan Chen, Shuyuan Yeh, Chawnshang Chang
Journal: Cancer Research (2014)

Abstract Males have a higher incidence of renal cell carcinoma (RCC) than females, but the reason for this gender difference is unknown. Addressing this question, we report the discovery of an androgen receptor (AR)–induced HIF2α/VEGF signal that drives RCC progression. AR attenuation or augmentation in RCC cells altered their proliferation, migration, and invasion in multiple models in vitro and in vivo. Mechanistic investigations revealed that AR targeting inhibited RCC cell migration and invasion by modulating HIF2α/VEGF signals at the level of mRNA and protein expression. Interrupting HIF2α/VEGF signals with inhibitors of either HIF2α or VEGF was sufficient to suppress RCC progression. Similarly, the specific AR degradation enhancer ASC-J9 was sufficient to suppress AR-induced HIF2α/VEGF signaling and RCC progression in multiple models in vitro and in vivo. Taken together, our results revealed a novel role for AR in RCC initiation and progression with implications for novel therapeutic strategies. Cancer Res; 74(16); 4420–30. ©2014 AACR.
Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer
Authors: Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Julia Balfour, Alberto Bardelli
Journal: JNCI Journal of the National Cancer Institute (2009)

The monoclonal antibodies panitumumab and cetuximab that target the epidermal growth factor receptor (EGFR) have expanded the range of treatment options for metastatic colorectal cancer. Initial evaluation of these agents as monotherapy in patients with EGFR-expressing chemotherapy-refractory tumors yielded response rates of approximately 10%. The realization that detection of positive EGFR expression by immunostaining does not reliably predict clinical outcome of EGFR-targeted treatment has led to an intense search for alternative predictive biomarkers. Oncogenic activation of signaling pathways downstream of the EGFR, such as mutation of KRAS, BRAF, or PIK3CA oncogenes, or inactivation of the PTEN tumor suppressor gene is central to the progression of colorectal cancer. Tumor KRAS mutations, which may be present in 35%–45% of patients with colorectal cancer, have emerged as an important predictive marker of resistance to panitumumab or cetuximab treatment. In addition, among colorectal tumors carrying wild-type KRAS, mutation of BRAF or PIK3CA or loss of PTEN expression may be associated with resistance to EGFR-targeted monoclonal antibody treatment, although these additional biomarkers require further validation before incorporation into clinical practice. Additional knowledge of the molecular basis for sensitivity or resistance to EGFR-targeted monoclonal antibodies will allow the development of new treatment algorithms to identify patients who are most likely to respond to treatment and could also provide rationale for combining therapies to overcome primary resistance. The use of KRAS mutations as a selection biomarker for anti-EGFR monoclonal antibody (eg, panitumumab or cetuximab) treatment is the first major step toward individualized treatment for patients with metastatic colorectal cancer.
Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent
Authors: Theresa Berndt, Theodore A. Craig, Ann E. Bowe, John Vassiliadis, David Reczek, Richard Finnegan, Suzanne M. Jan De Beur, Susan C. Schiavi, Rajiv Kumar
Journal: Journal of Clinical Investigation (2003)

Tumors associated with osteomalacia elaborate the novel factor(s), phosphatonin(s), which causes phosphaturia and hypophosphatemia by cAMP-independent pathways. We show that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, is a circulating phosphaturic factor that antagonizes renal Wnt-signaling. In cultured opossum renal epithelial cells, sFRP-4 specifically inhibited sodium-dependent phosphate transport. Infusions of sFRP-4 in normal rats over 2 hours specifically increased renal fractional excretion of inorganic phosphate (FEPi) from 14% ± 2% to 34% ± 5% (mean ± SEM, P < 0.01). Urinary cAMP and calcium excretion were unchanged. In thyro-parathyroidectomized rats, sFRP-4 increased FEPi from 0.7% ± 0.2% to 3.8% ± 1.2% (P < 0.05), demonstrating that sFRP-4 inhibits renal inorganic phosphate reabsorption by PTH-independent mechanisms. Administration of sFRP-4 to intact rats over 8 hours increased FEPi, decreased serum phosphate (1.95 ± 0.1 to 1.53 ± 0.09 mmol/l, P < 0.05) but did not alter serum 1α, 25-dihydroxyvitamin D, renal 25-hydroxyvitamin D 1α-hydroxylase cytochrome P450, and sodium-phosphate cotransporter mRNA concentrations. Infusion of sFRP-4 antagonizes Wnt action as demonstrated by reduced renal β-catenin and increased phosphorylated β-catenin concentrations. The sFRP-4 is detectable in normal human serum and in the serum of a patient with tumor-induced osteomalacia. Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1α, 25-dihydroxyvitamin D.
Phase I Clinical Trial of a HER-2/<i>neu</i> Peptide (E75) Vaccine for the Prevention of Prostate-Specific Antigen Recurrence in High-Risk Prostate Cancer Patients
Authors: Matthew T. Hueman, Zia A. Dehqanzada, Thomas E. Novak, Jennifer M. Gurney, Michael M. Woll, Gayle B. Ryan, Catherine E. Storrer, Christine Fisher, David G. McLeod, Constantine G. Ioannides, Sathibalan Ponniah, George E. Peoples
Journal: Clinical Cancer Research (2005)

The E75 peptide is an immunogenic peptide from the HER-2/neu protein that is substantially expressed in prostate cancer. We are conducting a clinical trial of an E75/granulocyte macrophage colony-stimulating factor vaccine to prevent post-prostatectomy prostate-specific antigen (PSA) recurrences in high-risk prostate cancer (HRPC) patients.Prostate cancer patients at high risk for recurrence were prospectively evaluated and identified by the validated Center for Prostate Disease Research (CPDR)/CaPSURE high-risk equation. From these high-risk equation patients, 27 HER-2/neu-expressing prostate cancer patients were enrolled. HLA-A2+ patients (n = 17) were vaccinated, whereas HLA-A2- patients (n = 10) were followed as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence were measured.This vaccine is safe with only minor toxicities observed. Additionally, the vaccine is immunogenic with all patients showing both in vivo and in vitro phenotypic and functional immune responses, although variable. HLA-A2+ patients were found to have larger tumors, higher postoperative Gleason scores, and more high-risk CPDR scores than HLA-A2- patients. Despite these differences, disease-free survival was not different between the vaccinated HLA-A2+ patients and the HLA-A2- controls at a median follow up of 23 months. Three of the four vaccinated patients that recurred had rising PSAs at the initiation of the trial. Ex vivo phenotypic assays were predictive of recurrences and correlated in general with functional assays.The E75 vaccine strategy is safe and effective in eliciting an immune response against the HER-2/neu protein in HRPC patients and may be useful as a preventive strategy against disease recurrence. Vaccination in response to a rising PSA may be too late.
CLINICAL PREDICTORS OF DISEASE PROGRESSION AND POOR PROGNOSIS OF APICAL HYPERTROPHIC CARDIOMYOPATHY
Authors: Jung-Woo Son, Sung-Jin Hong, Jung Myung Lee, Sung Yeol Jang, Jangwon Son, Chi Young Shim, Hyuk-Jae Chang, Geu-Ru Hong, Jong-Won Ha, Namsik Chung
Journal: Journal of the American College of Cardiology (2013)
Effect of methyldopa, clonidine, and hydralazine on cardiac mass and haemodynamics in Wistar Kyoto and spontaneously hypertensive rats
Authors: B. L PEGRAM, S. ISHISE, E. D FROHLICH
Journal: Cardiovascular Research (1982)

Journal Article Effect of methyldopa, clonidine, and hydralazine on cardiac mass and haemodynamics in Wistar Kyoto and spontaneously hypertensive rats Get access BARBARA L PEGRAM, BARBARA L PEGRAM * From the Alton Ochsner Medical Foundation, New Orleans, Louisiana *Requests for reprints should be sent to: Barbara L Pegram, Alton Ochsner Medical Foundation, 1516 Jefferson Highway, New Orleans, LA 70121, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar SHOZO ISHISE, SHOZO ISHISE From the Alton Ochsner Medical Foundation, New Orleans, Louisiana Search for other works by this author on: Oxford Academic PubMed Google Scholar EDWARD D FROHLICH EDWARD D FROHLICH From the Alton Ochsner Medical Foundation, New Orleans, Louisiana Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 1, January 1982, Pages 40–46, https://doi.org/10.1093/cvr/16.1.40 Published: 01 January 1982