tbuckley/cabot-search huggingface dataset:
Sleep quality in older adults: effects of exercise training and influence of sunlight exposure
Authors: Patrick J. O'Connor, Shawn D. Youngstedt
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Dr King and colleagues<sup>1</sup>reported that, following 16 weeks of exercise training, older adults with moderate sleep complaints exhibited self-reported reductions in sleep-onset latency and increases in sleep duration of approximately 15 minutes and 50 minutes per night, respectively. In an Editorial accompanying the article, Dr Buchner<sup>2</sup>stated, "The study found exercise caused improvements in sleep quality." This statement is not defensible scientifically because all plausible alternative explanations for these findings were not ruled out. The circadian system is a major determinant of both sleeponset latency and sleep duration. In older adults, an advanced circadian phase and a reduced circadian amplitude are thought to contribute to sleep disturbances.<sup>3</sup>Moreover, the weight of the available evidence suggests that exposure to bright light can be helpful in treating certain sleep problems in the elderly, presumably via a circadian mechanism because appropriately timed exposure to bright light
High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation for Recurrent or Refractory Pediatric Hodgkin's Disease: Results and Prognostic Indices
Authors: YeeYie E. Lieskovsky, Sarah S. Donaldson, Mylin A. Torres, Ruby M. Wong, Michael D. Amylon, Michael P. Link, Rajni Agarwal
Journal: Journal of Clinical Oncology (2004)

To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT).From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS).At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation).More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.
Guidelines for Thrombolytic Therapy for Acute Stroke: A Supplement to the Guidelines for the Management of Patients With Acute Ischemic Stroke
Authors: Harold P. Adams, Thomas G. Brott, Anthony J. Furlan, Camilo R. Gomez, James Grotta, Cathy M. Helgason, Thomas Kwiatkowski, Patrick D. Lyden, John R. Marler, James Torner, William Feinberg, Marc Mayberg, William Thies
Journal: Circulation (1996)
New approach to cancer therapy based on a molecularly defined cancer classification
Authors: Javier Cortés, Emiliano Calvo, Ana Vivancos, Jose Perez‐Garcia, Juan Angel Recio, Joan Seoane
Journal: CA A Cancer Journal for Clinicians (2013)

Translational and clinical cancer research, as well as clinical trials and treatment of cancer, are essentially structured based on the organ in which tumors originate. However, the recent explosion of knowledge about the molecular characteristics of tumors is opening a new way to tackle cancer. This article proposes a different approach to the classification of cancer with important implications for treatment and for basic, translational, and clinical research. The authors postulate that cancers from diverse organs of origin with similar molecular traits should be managed together. The common molecular features observed in different tumors determine clinical actions in a better way than organ-based classification. Thus, comparisons between tumors residing in different locations but with shared molecular characteristics will improve the therapeutic approach and the understanding of the biology of cancer.
Evolutionary and Molecular Facts Link the WWC Protein Family to Hippo Signaling
Authors: Dirk Oliver Wennmann, Jürgen Schmitz, Michael C. Wehr, Michael P. Krahn, Nora Koschmal, Sascha Gromnitza, Ulf Schulze, Thomas Weide, Anil Chekuri, Boris V. Skryabin, Volker Gerke, Hermann Pavenstädt, Kerstin Duning, Joachim Kremerskothen
Journal: Molecular Biology and Evolution (2014)

The scaffolding protein KIBRA (also called WWC1) is involved in the regulation of important intracellular transport processes and the establishment of cell polarity. Furthermore, KIBRA/WWC1 is an upstream regulator of the Hippo signaling pathway that controls cell proliferation and organ size in animals. KIBRA/WWC1 represents only one member of the WWC protein family that also includes the highly similar proteins WWC2 and WWC3. Although the function of KIBRA/WWC1 was studied intensively in cells and animal models, the importance of WWC2 and WWC3 was not yet elucidated. Here, we describe evolutionary, molecular, and functional aspects of the WWC family. We show that the WWC genes arose in the ancestor of bilateral animals (clades such as insects and vertebrates) from a single founder gene most similar to the present KIBRA/WWC1-like sequence of Drosophila. This situation was still maintained until the common ancestor of lancelet and vertebrates. In fish, a progenitor-like sequence of mammalian KIBRA/WWC1 and WWC2 is expressed together with WWC3. Finally, in all tetrapods, the three family members, KIBRA/WWC1, WWC2, and WWC3, are found, except for a large genomic deletion including WWC3 in Mus musculus. At the molecular level, the highly conserved WWC proteins share a similar primary structure, the ability to form homo- and heterodimers and the interaction with a common set of binding proteins. Furthermore, all WWC proteins negatively regulate cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP, the major effector of the Hippo pathway.
Once-daily tiotropium respimat add-on to ICS±LABA improves control across asthma severities
Authors: J. Mark FitzGerald, Huib Kerstjens, Pierluigi Paggiaro, Ken Ohta, Masakazu Ichinose, Petra Moroni-Zentgraf, Michael Engel, Hendrik Schmidt, Eric Bateman
Journal: European Respiratory Journal (2014)

Background:  Tiotropium Respimat added to ICS±LABA has been investigated across asthma severities. We present ACQ-7 responses from six Phase III randomised, double-blind, placebo-controlled, parallel-group trials in patients with symptomatic asthma.   Methods:  Two 48-wk trials (PrimoTinA): 5µg added to ICS (≥800µg budesonide or equivalent [bud or eq])+LABA; two 24-wk trials (MezzoTinA): 5/2.5µg added to ICS (400–800µg bud or eq); 12-wk trial (GraziaTinA): 5/2.5µg added to ICS (200–400µg bud or eq); 52-wk trial (Study 464): 5/2.5µg added to ICS (400–800µg bud or eq). ACQ-7 responder rates were pre-specified in MezzoTinA, GraziaTinA and Study 464; ACQ-7 change from baseline (response) was pre-specified in PrimoTinA.   Results:  Mean baseline ACQ-7 (SD): PrimoTinA 2.63 (0.69); MezzoTinA 2.18 (0.49); GraziaTinA 2.10 (0.42); Study 464 1.95 (0.39). ACQ-7 responder rate data are presented (Table). Adjusted mean response difference vs placebo Respimat±SE: PrimoTinA, 5µg −0.132±0.049 (p=0.007); MezzoTinA, 5µg −0.115±0.043 (p=0.008), 2.5µg −0.160±0.043 (p   Conclusion:  Once-daily tiotropium Respimat add-on to at least ICS maintenance therapy was associated with improved asthma control across severities.
THE NATURE OF NON-SPECIFIC INHIBITION OF VIRUS HEMAGGLUTINATION
Authors: William F. Friedewald, Edward S. Miller, L. Ross Whatley
Journal: The Journal of Experimental Medicine (1947)

A study of the component in serum and tissue extracts responsible for non-specific inhibition of hemagglutination with mumps virus and the PR8 and Lee strains of influenza virus has yielded the following results: 1. The inhibitory factor was found in high titer in human serum and in saline extracts of various organs procured at autopsy (lung, liver,kidney, spleen). The inhibition titers of extracts of these organs were usually higher than the serum titers, whereas the titers of muscle extracts were invariably lower. 2. Similar results were obtained with serum and tissue extracts from normal rabbits and guinea pigs. 3. The serum inhibition titers were not affected by heating to 75 degrees C. for 30 minutes, whereas the titers of the tissue extracts were usually reduced by heating at 65 degrees C. or 75 degrees C. for 30 minutes. 4. Saline extracts of human and chicken red blood cells also contained an inhibitory substance in high titer, and these cells showed marked agglutination with influenza and mumps viruses. Rabbit red cells, on the other band, underwent little or no agglutination with these viruses and extracts of these cells failed to cause inhibition. Sheep red cells varied in their capacity to agglutinate and also in their yield of the inhibitory substance. 5. When the virus receptor substance was removed from chicken red cells by adsorption and elution with influenza virus, extracts of the cells no longer yielded the inhibitory factor. 6. The inhibitory substance did not neutralize influenza virus in mice and it failed to fix complement when mixed with influenza or mumps viruses. 7. Evidence was obtained that some virus was released from the inhibitory substance after incubation for 6 hours at 22 degrees C. or 37 degrees C. The implications of these findings are discussed.
Influence of ventricular morphology on aerobic exercise capacity in patients after the Fontan operation
Authors: Hideo Ohuchi, Kenji Yasuda, Satoshi Hasegawa, Aya Miyazaki, Motoki Takamuro, Osamu Yamada, Yasuo Ono, Hideki Uemura, Toshikatsu Yagihara, Shigeyuki Echigo
Journal: Journal of the American College of Cardiology (2001)
Vasorelaxation by Red Blood Cells and Impairment in Diabetes
Authors: Philip E. James, Derek Lang, Timothy Tufnell-Barret, Alex B. Milsom, Michael P. Frenneaux
Journal: Circulation Research (2004)

Vascular dysfunction in diabetes is attributed to lack of bioavailable nitric oxide (NO) and is postulated as a primary cause of small vessel complications as a result of poor glycemic control. Although it has been proposed that NO is bound by red blood cells (RBCs) and can induce relaxation of blood vessels distal to its site of production in the normal circulation, the effect of RBC glycation on NO binding and relaxation of hypoxic vessels is unknown. We confirm RBC-induced vessel relaxation is inversely related to tissue oxygenation and is proportional to RBC S -nitrosohemoglobin (HbSNO) content (but not nitrosylhemoglobin content). We show more total NO bound inside highly glycated RBCs (0.0134 versus 0.0119 NO/Hb, respectively; P &lt;0.05) although proportionally less HbSNO (0.0053 versus 0.0088 NO/Hb, respectively; P &lt;0.05). We also show glycosylation impairs the vasodilator function of RBCs within a physiological range of tissue oxygenation. These findings may represent an important contribution to reduced NO bioavailability in the microvasculature in diabetes.
Follow-up Prostate Cancer Treatments After Radical Prostatectomy: a Population-Based Study
Authors: G. L. Lu-Yao, A. L. Potosky, P. C. Albertsen, J. H. Wasson, M. J. Barry, J. E. Wennberg
Journal: JNCI Journal of the National Cancer Institute (1996)

Radical prostatectomy is one of the most commonly used curative procedures for the treatment of localized prostate cancer. The probability that a patient will undergo additional cancer therapy after this procedure is largely unknown. The objective was to determine the likelihood of additional cancer therapy after radical prostatectomy. Data for this study were derived from a linked dataset that combined information from the Surveillance, Epidemiology, and End Results Program and Medicare hospital and physician claims. Records were included in this study if patient histories met the following criteria: ( a ) residing in Connecticut, Washington (Seattle-Puget Sound), or Georgia (Metropolitan Atlanta); ( b ) having been diagnosed with prostate cancer during the period from January 1, 1985, through December 31, 1991; ( c ) undergoing radical prostatectomy by December 31, 1992; and ( d ) having no evidence of other types of cancer. Patients were considered to have had additional cancer therapy if they had had radiation therapy, orchiectomy, and/or androgen-deprivation therapy by injection after radical prostatectomy. The interval between the initial treatment and any follow-up treatment was calculated from the date of radical prostatectomy to the 1st day of the follow-up cancer therapy. All presented probabilities are based on Kaplan—Meier estimates. The study population consisted of 3494 Medicare patients, 3173 of whom underwent radical prostatectomy within 3 months of prostate cancer diagnosis. Although radical prostatectomy is often reserved for localized cancer, less than 60% (1934) of patients whose records were included in this study had organ-confined disease, according to final surgical pathology. Overall, the 5-year cumulative incidence of having any additional cancer treatment after radical prostatectomy reached 34.9% (95% confidence interval [CI] = 31.5%–38.5%). For patients with pathologically organ-confined cancer, the 5-year cumulative incidence was 24.3% (95% CI = 20.0%–29.3%) overall and ranged from 15.6% (95% CI = 9.7%–24.5%) for well-differentiated cancer (Gleason scores 2–4) to 41.5% (95% CI = 27.9%–58.4%) for poorly differentiated cancer (Gleason scores 8–10). The corresponding figures for pathologically regional cancer were 22.7% (95% CI = 12.0%–40.5%) and 68.1% (95% CI = 58.7%–77.1%). Further treatment of prostate cancer was done in about one third of patients who had had a radical prostatectomy with curative intent and in about one quarter of patients who were found to have organ-confined disease. Given the common requirement for follow-up cancer treatments after radical prostatectomy and the uncertainties about the effectiveness of the various follow-up treatment strategies, further investigation of these treatments is warranted. [J Natl Cancer Inst 1996;88:166–73]
Germinal center reutilization by newly activated B cells
Authors: Tanja A. Schwickert, Boris Alabyev, Tim Manser, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2009)

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude that GCs are dynamic anatomical structures that can be reutilized by newly activated B cells during immune responses.
Occupational Risks of Bladder Cancer in the United States: II. Nonwhite Men
Authors: D. T. Silverman, L. I. Levin, R. N. Hoover
Journal: JNCI Journal of the National Cancer Institute (1989)

Occupational risks of bladder cancer among nonwhite men were assessed based on interviews with 126 cases and 383 controls conducted during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. Our findings indicated that nonwhite men who were ever employed as auto workers have an elevated risk of bladder cancer (relative risk (RR) =2.3; 95% confidence intervals (CI) = 0.8–6.4) with a significant positive trend in RR with increasing duration of employment (P=.017) and with the RR rising to 4.7 for those employed at least 10 years. Dry cleaners, ironers, and pressers also experienced increased bladder cancer risk (RR=2.8, CI = 1.1–7.4). Nonsignificant excesses of similar magnitude to those seen among white men were found for nonwhite men employed in several other occupations. Overall, our findings suggest that the risk of occupational bladder cancer among white and nonwhite men is similar. When inconsistencies between whites and nonwhites did occur, they appeared either due to chance or possibly racial differences in exposure among men within the same industry and occupation. In all, we estimate that the population attributable risk for occupation among nonwhite U.S. men is 27% (CI = 9% to 56%), which is slightly higher than the estimate of 21% to 25% previously reported for white U.S. men, although this difference was not statistically significant. [J Natl Cancer Inst 81: 1480–1483, 1989]
Erysipelas and necrotizing fasciitis
Authors: HANS HAMMAR, LENA WANGER
Journal: British Journal of Dermatology (1977)

The clinical course of necrotizing fasciitis in 8 patients is compared with observations on 22 other patients with erysipelas. In necrotizing fasciitis the early erythematous areas turn into a dusky blue colour with later vesiculation and formation of bullae. An important finding is a non-pitting oedema extending outside the erythematous patches. The disease often progresses and involves further skin areas proximal to the initial ones. Gangrene tends to follow in multiple sites after the 1st week of illness. Group A streptococci in conjunction with widespread thrombosis and vascular necrosis of the involved skin are two major factors in the pathogenesis of the gangrene. Early debridement and excision of necrotic tissue in combination with large doses of penicillin and cloxacillin are confirmed as mandatory to remove toxaemia and inhibit further necrosis of the skin. In 3 of the 8 patients with necrotizing fasciitis the syndrome of disseminated intravascular coagulation complicated the course of the disease. A promising therapeutic result was seen in 2 further patients exhibiting alarming signs and symptoms of early necrotizing fasciitis; the combination of heparin, given intravenously in therapeutic doses guided by activated partial thromboplastin time studies, and of systemic antibiotics alleviated the symptoms, which vanished within 10 days of the start of treatment.
Dramatic Mitochondrial Gene Rearrangements in the Hermit Crab Pagurus longicarpus (Crustacea, Anomura)
Authors: M. J. Hickerson, C. W. Cunningham
Journal: Molecular Biology and Evolution (2000)

The entire mitochondrial gene order of the crustacean Pagurus longicarpus was determined by sequencing all but approximately 300 bp of the mitochondrial genome. We report the first major gene rearrangements found in the clade including Crustacea and Insecta. At least eight mitochondrial gene rearrangements have dramatically altered the gene order of the hermit crab P. longicarpus relative to the putatively ancestral crustacean gene order. These include two rearrangements of protein-coding genes, the first reported for any nonchelicerate arthropod. Codon usage and amino acid sequences do not deviate substantially from those reported for other crustaceans. Investigating the phylogenetic distribution of these eight rearrangements will add additional characters to help resolve decapod phylogeny.
Selective Activation of Oxygen-Deprived Tumor-Infiltrating Lymphocytes through Local Intratumoral Delivery of CD137 Monoclonal Antibodies
Authors: Cornelis J.M. Melief
Journal: Cancer Discovery (2012)

Abstract Summary: Hypoxia-inducing transcription factor-1α (HIF-1α) in hypoxic tumors induces the TNF receptor family member CD137 on tumor-infiltrating lymphocytes. This can be exploited for intratumoral low-dose injection of effective systemic immunotherapy with agonist CD137-specific monoclonal antibodies that induce circulation of systemic tumor-specific effector T cells capable of eradicating distant metastases. Cancer Discov; 2(7); 586–7. ©2012 AACR. Commentary on Palazón et al., p. 608.
Androgen Receptor Expression and Outcomes in Early Breast Cancer: A Systematic Review and Meta-Analysis
Authors: F. E. Vera-Badillo, A. J. Templeton, P. de Gouveia, I. Diaz-Padilla, P. L. Bedard, M. Al-Mubarak, B. Seruga, I. F. Tannock, A. Ocana, E. Amir
Journal: JNCI Journal of the National Cancer Institute (2013)

The androgen receptor (AR) is expressed frequently in breast cancer, but its prognostic significance is unclear. Preclinical data suggest that expression of AR may modify clinical outcomes in early breast cancer with improved prognosis in estrogen receptor (ER)-positive disease and poorer prognosis in ER-negative disease.A systematic review of electronic databases was conducted to identify studies published between 1946 and July 2012 and to explore the association between AR expression and overall survival (OS) and disease-free survival (DFS) in women diagnosed with early breast cancer. The odds ratios (OR) for OS and DFS at 3 and 5 years were calculated and then weighted and pooled in a meta-analysis with Mantel-Haenszel random-effect modeling. All statistical tests were two-sided.Nineteen studies with a total of 7693 women were included. AR expression was documented in 60.5% of patients. ER-positive tumors were more likely to express AR- than ER-negative tumors (74.8% vs 31.8%, χ(2) P < .001). Compared with tumors without AR expression, those expressing AR were associated with improved OS at both 3 and 5 years (OR = 0.47, 95% confidence interval [CI] = 0.39 to 0.58, P < .001; and OR = 0.40, 95% CI = 0.29 to 0.56, P < .001). The absolute differences in the probability of OS at 3 and 5 years were 6.7% (95% CI = 3.5% to 9.8%) and 13.5% (95% CI = 7.5% to 19.6%), respectively. Results for 3- and 5-year DFS were similar. Coexpression of the ER did not influence OS at 3 or at 5 years.Expression of AR in women with breast cancer is associated with better OS and DFS irrespective of coexpression of ER.