tbuckley/cabot-search huggingface dataset:
Associations Between End-of-Life Discussions, Patient Mental Health, Medical Care Near Death, and Caregiver Bereavement Adjustment
Authors: Alexi A. Wright
Journal: JAMA (2008)

Talking about death can be difficult. Without evidence that end-of-life discussions improve patient outcomes, physicians must balance their desire to honor patient autonomy against a concern of inflicting psychological harm.To determine whether end-of-life discussions with physicians are associated with fewer aggressive interventions.A US multisite, prospective, longitudinal cohort study of patients with advanced cancer and their informal caregivers (n = 332 dyads), September 2002-February 2008. Patients were followed up from enrollment to death, a median of 4.4 months later. Bereaved caregivers' psychiatric illness and quality of life was assessed a median of 6.5 months later.Aggressive medical care (eg, ventilation, resuscitation) and hospice in the final week of life. Secondary outcomes included patients' mental health and caregivers' bereavement adjustment.One hundred twenty-three of 332 (37.0%) patients reported having end-of-life discussions before baseline. Such discussions were not associated with higher rates of major depressive disorder (8.3% vs 5.8%; adjusted odds ratio [OR], 1.33; 95% confidence interval [CI], 0.54-3.32), or more worry (mean McGill score, 6.5 vs 7.0; P = .19). After propensity-score weighted adjustment, end-of-life discussions were associated with lower rates of ventilation (1.6% vs 11.0%; adjusted OR, 0.26; 95% CI, 0.08-0.83), resuscitation (0.8% vs 6.7%; adjusted OR, 0.16; 95% CI, 0.03-0.80), ICU admission (4.1% vs 12.4%; adjusted OR, 0.35; 95% CI, 0.14-0.90), and earlier hospice enrollment (65.6% vs 44.5%; adjusted OR, 1.65;95% CI, 1.04-2.63). In adjusted analyses, more aggressive medical care was associated with worse patient quality of life (6.4 vs 4.6; F = 3.61, P = .01) and higher risk of major depressive disorder in bereaved caregivers (adjusted OR, 3.37; 95% CI, 1.12-10.13), whereas longer hospice stays were associated with better patient quality of life (mean score, 5.6 vs 6.9; F = 3.70, P = .01). Better patient quality of life was associated with better caregiver quality of life at follow-up (beta = .20; P = .001).End-of-life discussions are associated with less aggressive medical care near death and earlier hospice referrals. Aggressive care is associated with worse patient quality of life and worse bereavement adjustment.
Legionella pneumophila Is Internalized by a Macropinocytotic Uptake Pathway Controlled by the Dot/Icm System and the Mouse Lgn1 Locus✪
Authors: Masahisa Watarai, Isabelle Derre, James Kirby, Joseph D. Growney, William F. Dietrich, Ralph R. Isberg
Journal: The Journal of Experimental Medicine (2001)

The products of the Legionella pneumophila dot/icm genes enable the bacterium to replicate within a macrophage vacuole. This study demonstrates that the Dot/Icm machinery promotes macropinocytotic uptake of L. pneumophila into mouse macrophages. In mouse strains harboring a permissive Lgn1 allele, L. pneumophila promoted formation of vacuoles that were morphologically similar to macropinosomes and dependent on the presence of an intact Dot/Icm system. Macropinosome formation appeared to occur during, rather than after, the closure of the plasma membrane about the bacterium, since a fluid-phase marker preloaded into the macrophage endocytic path failed to label the bacterium-laden macropinosome. The resulting macropinosomes were rich in GM1 gangliosides and glycosylphosphatidylinositol-linked proteins. The Lgn1 allele restrictive for L. pneumophila intracellular replication prevented dot/icm-dependent macropinocytosis, with the result that phagosomes bearing the microorganism were targeted into the endocytic network. Analysis of macrophages from recombinant inbred mouse strains support the model that macropinocytotic uptake is controlled by the Lgn1 locus. These results indicate that the products of the dot/icm genes and Lgn1 are involved in controlling an internalization route initiated at the time of bacterial contact with the plasma membrane.
A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered-dose inhalers
Authors: Peter S. Creticos, Wallace P. Adams, Brent G. Petty, Lionel D. Lewis, Gur Jai Pal Singh, Arouna P. Khattignavong, Justina A. Molzon, Marilyn N. Martinez, Paul S. Lietman, Roger L. Williams
Journal: Journal of Allergy and Clinical Immunology (2002)
Enhancement of Docetaxel Anticancer Activity by a Novel Diindolylmethane Compound in Human Non–Small Cell Lung Cancer
Authors: Nkechi Ichite, Mahavir B. Chougule, Tanise Jackson, Suniket V. Fulzele, Stephen Safe, Mandip Singh
Journal: Clinical Cancer Research (2009)

Abstract Purpose: This study was conducted to examine the cytotoxic effects of a peroxisome proliferator-activated receptor γ (PPARγ) agonist, 1,1-bis (3′-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC6H5), alone and in combination with docetaxel in vitro in A549 lung cancer cells and in vivo in nude mice bearing A549 orthotopic lung tumors. Experimental Design: Isobolographic method was used to calculate combination index values from cell viability data. Apoptosis was evaluated in A549 cells by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and measurement of cleaved poly(ADP-ribose) polymerase level. Expression of proteins was studied by Western blotting. A549 cells were implanted to induce orthotopic lung tumors in nude mice and the efficacy of docetaxel, DIM-C-pPhC6H5, or combination was determined. Apoptosis and cleaved caspase-3 expression in the harvested tissues were studied by terminal deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemistry, respectively. Results: The combination index values (0.36-0.9) suggested synergistic to additive effects of docetaxel + DIM-C-pPhC6H5 and resulted in the highest increase in percentage of apoptotic cells and expression of cleaved poly(ADP-ribose) polymerase, Bax, and N-cadherin compared with treatment with either agent. The combination also enhanced procaspase-3 and -9 cleavage. In vivo, docetaxel + DIM-C-pPhC6H5 reduced lung weights by 57% compared with 39% by docetaxel or 22% by DIM-C-pPhC6H5 alone, induced apoptosis in 43% of the tumor cells compared with 29% and 22% in tumors treated with docetaxel and DIM-C-pPhC6H5, respectively, and increased procaspase-3 cleavage compared with either agent alone. Conclusions: These findings suggest potential benefit for use of docetaxel and DIM-C-pPhC6H5 combination in lung cancer treatment.
Clusterin Expression in Non-neoplastic Adenohypophyses and Pituitary Adenomas: Cytoplasmic Clusterin Localization in Adenohypophysis is Related to Aging
Authors: A. Işın Doğan Ekici, Bülent Eren, Nursel Türkmen, Nil Çomunoğlu, Recep Fedakar
Journal: Endocrine Pathology (2008)
Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study
Authors: Maylene Wong, Lidia Staszewsky, Roberto Latini, Simona Barlera, Alberto Volpi, Yann-Tong Chiang, Raymond L Benza, Sidney O Gottlieb, Thomas D Kleemann, Franco Rosconi, Pieter M Vandervoort, Jay N Cohn
Journal: Journal of the American College of Cardiology (2002)
A molecular phylogeny for aplocheiloid fishes (Atherinomorpha, Cyprinodontiformes): the role of vicariance and the origins of annualism
Authors: W. J. Murphy, G. E. Collier
Journal: Molecular Biology and Evolution (1997)

Annual aplocheiloid killifish embryos possess a rare ability among vertebrates to enter stages of developmental arrest (diapause) when subjected to adverse environmental conditions. Previous morphological analyses have presented disparate hypotheses regarding the evolution of the intriguing life history associated with this phenomenon. We present a novel hypothesis of aplocheiloid relationships based on 1,009 bp of sequence data from three mitochondrial genes (cytochrome b, 12S rRNA, and 16S rRNA). Phylogenetic analysis using maximum parsimony, neighbor-joining, and maximum likelihood produce strongly congruent topologies. Our data confirm the monophyly of the Neotropical family Rivulidae, while demonstrating a paraphyletic Old World assemblage. The basal sister group position of Indo-Malaysian and Madagascaran taxa relative to a monophyletic South American/African dichotomy strongly indicates the role of vicariance in the diversification of these fishes in spite of their definition as secondary freshwater fish. The distribution of annualism onto this topology implies a single early origin for this suite of characters, prior to the divergence of South American and African taxa. If so, then annualism has since been lost several times during the evolution of genera now residing in permanent aquatic habitats. Paleoclimatic knowledge complements this scenario based on molecular characters.
Cognition in the Early Stage of Type 2 Diabetes
Authors: Carla Ruis, Geert Jan Biessels, Kees J. Gorter, Maureen van den Donk, L. Jaap Kappelle, Guy E.H.M. Rutten
Journal: Diabetes Care (2009)

Type 2 diabetes is known to be associated with decrements in memory and executive functions and information-processing speed. It is less clear, however, at which stage of diabetes these cognitive decrements develop and how they progress over time. In this study, we investigated cognitive functioning of patients with recent screen-detected type 2 diabetes, thus providing insight into the nature and severity of cognitive decrements in the early stage of the disease. Possible risk factors were also addressed.Included in this study were 183 diabetic patients from a previously established study cohort and 69 control subjects. A full neuropsychological assessment, addressing six cognitive domains, was made for each participant. Raw test scores were standardized into z scores per domain and compared between the groups. Possible risk factors for cognitive decrements were examined with multivariate linear regression.Relative to scores for the control group, mean z scores were between 0.01 and 0.2 lower in the diabetic group across all domains, but after adjustment for differences in IQ between patients and control subjects, only memory performance was significantly reduced (mean difference -0.15 [95% CI -0.28 to -0.03]). A history of macrovascular disease and current smoking were significant determinants of slower information-processing speed in patients with diabetes.This study shows that modest cognitive decrements are already present at the early stage of type 2 diabetes. A history of macrovascular disease and smoking are significant risk factors for some early decrements.
Resistant or Difficult-to-Control Hypertension
Authors: Marvin Moser, John F. Setaro
Journal: New England Journal of Medicine (2006)

A 70-year-old woman with a long-standing history of hypertension comes for follow-up. Her medications include atenolol (100 mg daily), hydrochlorothiazide (12.5 mg daily), lisinopril (40 mg daily), and ibuprofen (400 mg twice daily for osteoarthritis). She does not smoke or drink alcohol. Her body-mass index is 32. Her blood pressure (measured three times while she is seated) ranges from 164/92 to 170/96 mm Hg; her pulse rate is 72 per minute. Examination of her ocular fundi reveals arteriolar narrowing. The results of cardiovascular examination are normal. How should she be further evaluated and treated?
ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel disease in humans and mice
Authors: Lin-Yan Huang, Qing He, Si-Jia Liang, Ying-Xue Su, Li-Xiong Xiong, Qian-Qian Wu, Qin-Yan Wu, Jing Tao, Jian-Ping Wang, Yong-Bo Tang, Xiao-Fei Lv, Jie Liu, Yong-Yuan Guan, Rui-Ping Pang, Jia-Guo Zhou
Journal: Gut (2014)

<h3>Background</h3> ClC-3 channel/antiporter plays a critical role in a variety of cellular activities. ClC-3 has been detected in the ileum and colon. <h3>Objective</h3> To determine the functions of ClC-3 in the gastrointestinal tract. <h3>Design</h3> After administration of dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), intestines from ClC-3−/− and wild-type mice were examined by histological, cellular, molecular and biochemical approaches. ClC-3 expression was determined by western blot and immunostaining. <h3>Results</h3> ClC-3 expression was reduced in intestinal tissues from patients with UC or Crohn9s disease and from mice treated with DSS. Genetic deletion of ClC-3 increased the susceptibility of mice to DSS- or TNBS-induced experimental colitis and prevented intestinal recovery. ClC-3 deficiency promoted DSS-induced apoptosis of intestinal epithelial cells through the mitochondria pathway. ClC-3 interacts with voltage-dependent anion channel 1, a key player in regulation of mitochondria cytochrome c release, but DSS treatment decreased this interaction. In addition, lack of ClC-3 reduced the numbers of Paneth cells and impaired the expression of antimicrobial peptides. These alterations led to dysfunction of the epithelial barrier and invasion of commensal bacteria into the mucosa. <h3>Conclusions</h3> A defect in ClC-3 may contribute to the pathogenesis of IBD by promoting intestinal epithelial cell apoptosis and Paneth cell loss, suggesting that modulation of ClC-3 expression might be a new strategy for the treatment of IBD.
Induction of CD8<sup>+</sup>T-Cell Responses Against Novel Glioma–Associated Antigen Peptides and Clinical Activity by Vaccinations With α-Type 1 Polarized Dendritic Cells and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Patients With Recurrent Malignant Glioma
Authors: Hideho Okada, Pawel Kalinski, Ryo Ueda, Aki Hoji, Gary Kohanbash, Teresa E. Donegan, Arlan H. Mintz, Johnathan A. Engh, David L. Bartlett, Charles K. Brown, Herbert Zeh, Matthew P. Holtzman, Todd A. Reinhart, Theresa L. Whiteside, Lisa H. Butterfield, Ronald L. Hamilton, Douglas M. Potter, Ian F. Pollack, Andres M. Salazar, Frank S. Lieberman
Journal: Journal of Clinical Oncology (2010)

A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2(+) patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100.Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 10(7)/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays.The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression.These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.
5-Lipoxygenase Is a Candidate Target for Therapeutic Management of Stem Cell–like Cells in Acute Myeloid Leukemia
Authors: Jessica Roos, Claudia Oancea, Maria Heinssmann, Dilawar Khan, Hannelore Held, Astrid S. Kahnt, Ricardo Capelo, Estel la Buscató, Ewgenij Proschak, Elena Puccetti, Dieter Steinhilber, Ingrid Fleming, Thorsten J. Maier, Martin Ruthardt
Journal: Cancer Research (2014)

Nonsteroidal anti-inflammatory drugs such as sulindac inhibit Wnt signaling, which is critical to maintain cancer stem cell-like cells (CSC), but they also suppress the activity of 5-lipoxygenase (5-LO) at clinically feasible concentrations. Recently, 5-LO was shown to be critical to maintain CSC in a model of chronic myeloid leukemia. For these reasons, we hypothesized that 5-LO may offer a therapeutic target to improve the management of acute myeloid leukemia (AML), an aggressive disease driven by CSCs. Pharmacologic and genetic approaches were used to evaluate the effects of 5-LO blockade in a PML/RARα-positive model of AML. As CSC models, we used Sca-1(+)/lin(-) murine hematopoietic stem and progenitor cells (HSPC), which were retrovirally transduced with PML/RARα. We found that pharmacologic inhibition of 5-LO interfered strongly with the aberrant stem cell capacity of PML/RARα-expressing HSPCs. Through small-molecule inhibitor studies and genetic disruption of 5-LO, we also found that Wnt and CSC inhibition is mediated by the enzymatically inactive form of 5-LO, which hinders nuclear translocation of β-catenin. Overall, our findings revealed that 5-LO inhibitors also inhibit Wnt signaling, not due to the interruption of 5-LO-mediated lipid signaling but rather due to the generation of a catalytically inactive form of 5-LO, which assumes a new function. Given the evidence that CSCs mediate AML relapse after remission, eradication of CSCs in this setting by 5-LO inhibition may offer a new clinical approach for immediate evaluation in patients with AML. Cancer Res; 74(18); 5244-55. ©2014 AACR.
Active Smoking and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study II Nutrition Cohort
Authors: Baiyu Yang, Eric J. Jacobs, Susan M. Gapstur, Victoria Stevens, Peter T. Campbell
Journal: Journal of Clinical Oncology (2015)

Active smoking is associated with higher colorectal cancer risk, but its association with survival after colorectal cancer diagnosis is unclear. We investigated associations of smoking, before and after diagnosis, with all-cause and colorectal cancer-specific mortality among colorectal cancer survivors.From a cohort of adults who were initially free of colorectal cancer, we identified 2,548 persons diagnosed with invasive, nonmetastatic colorectal cancer between baseline (1992 or 1993) and 2009. Vital status and cause of death were determined through 2010. Smoking was self-reported on the baseline questionnaire and updated in 1997 and every 2 years thereafter. Postdiagnosis smoking information was available for 2,256 persons (88.5%).Among the 2,548 colorectal cancer survivors, 1,074 died during follow-up, including 453 as a result of colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, prediagnosis current smoking was associated with higher all-cause mortality (relative risk [RR], 2.12; 95% CI, 1.65 to 2.74) and colorectal cancer-specific mortality (RR, 2.14; 95% CI, 1.50 to 3.07), whereas former smoking was associated with higher all-cause mortality (RR, 1.18; 95% CI, 1.02 to 1.36) but not with colorectal cancer-specific mortality (RR, 0.89; 95% CI, 0.72 to 1.10). Postdiagnosis current smoking was associated with higher all-cause (RR, 2.22; 95% CI, 1.58 to 3.13) and colorectal cancer-specific mortality (RR, 1.92; 95% CI, 1.15 to 3.21), whereas former smoking was associated with all-cause mortality (RR, 1.21; 95% CI, 1.03 to 1.42).This study adds to the existing evidence that cigarette smoking is associated with higher all-cause and colorectal cancer-specific mortality among persons with nonmetastatic colorectal cancer.
Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells
Authors: Marco Valgimigli, Laura Agnoletti, Salvatore Curello, Laura Comini, Gloria Francolini, Francesca Mastrorilli, Elisa Merli, Roberto Pirani, Gabriele Guardigli, Pier Giovanni Grigolato, Roberto Ferrari
Journal: Circulation (2003)

Endothelial apoptosis of atherosclerotic lesions is a possible determinant for the stable-to-vulnerable plaque transition. Recent data support the notion that plaque activation may be a pan-coronary process, advocating the existence of circulating triggers.Serum from 40 healthy subjects (group 1) and 73 patients with stable angina (n=32; group 2) or acute coronary syndromes (n=41; group 3) was incubated with human umbilical vein endothelial cells. The percentage of apoptosis by flow cytometry and Fas, Bax, and Bcl-2 protein expression by immunoblotting were evaluated at entry in patients and control subjects and repeated after 12 months in group 3. At baseline, apoptotic nuclei were higher in group 3 (14+/-6%) than in group 2 (3.3+/-1.8%) and group 1 (1.35+/-0.8%) (P<0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (P<0.01). Coincubation of group 3 serum with anti-tumor necrosis factor-alpha and anti-interleukin-6 monoclonal antibodies did not affect the human umbilical vein endothelial cell apoptotic process, whereas addition of Trolox decreased apoptosis to <50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (r=0.58, P<0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (P<0.0001, P<0.05 respectively).Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells, supporting the theory of the existence of circulating triggers potentially able to activate atherosclerotic lesions.
Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial
Authors: Lennart Hansson, Alberto Zanchetti, S George Carruthers, Björn Dahlöf, Dag Elmfeldt, Stevo Julius, Joël Ménard, Karl Heinz Rahn, Hans Wedel, Sten Westerling
Journal: The Lancet (1998)
Semimonthly Versus Monthly Regimen of Fluorouracil and Leucovorin Administered for 24 or 36 Weeks as Adjuvant Therapy in Stage II and III Colon Cancer: Results of a Randomized Trial
Authors: Thierry André, Philippe Colin, Christophe Louvet, Erik Gamelin, Olivier Bouche, Emmanuel Achille, Nicolas Colbert, Catherine Boaziz, Pascal Piedbois, Nicole Tubiana-Mathieu, Arnaud Boutan-Laroze, Michel Flesch, Marc Buyse, Aimery de Gramont
Journal: Journal of Clinical Oncology (2003)

This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer.LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion.A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001).Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.