tbuckley/cabot-search huggingface dataset:
Coach development programmes to improve interpersonal coach behaviours: a systematic review using the re-aim framework
Authors: M Blair Evans, Matthew McGuckin, Heather L Gainforth, Mark W Bruner, Jean Côté
Journal: British Journal of Sports Medicine (2015)

Although evidence supports the effectiveness of interpersonal Coach Development Programmes (CDPs), which are designed to foster coach-athlete relationships, an intervention's impact is shaped by numerous factors over and above effectiveness. The purpose of this systematic review was to examine the extent that published articles describing interpersonal CDP trials reported on indicators of internal and external validity, as conceptualised in the RE-AIM framework (ie, Reach, Effectiveness, Adoption, Implementation and Maintenance).The search strategy was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, involving a database search and supplemental manual search of key articles and journals. After initial screening, the full-text search strategy involved identifying articles describing CDP trials and then selecting a specific subgroup of articles involving interpersonal CDP trials and excluding ineligible articles. Resulting trials were coded using a 47-item sport coaching adaptation of the RE-AIM coding sheet.17 published articles met eligibility criteria, representing 10 distinct CDP trials. After attaining coder agreement, global ratings of RE-AIM indicators within interpersonal CDP trials ranged from the low to moderate quality. Whereas indicators of effectiveness and implementation were reported to some extent across all studies, maintenance within sport organisations and a number of specific indicators from across dimensions were rarely reported.These findings inform the future design and evaluation of CDPs that have the potential to be adopted in numerous settings and reach athletes and coaches who can most benefit.
Inhibiting MEK in MAPK pathway-activated myeloma
Authors: C J Heuck, Y Jethava, R Khan, F van Rhee, M Zangari, S Chavan, K Robbins, S E Miller, A Matin, M Mohan, S M Ali, P J Stephens, J S Ross, V A Miller, F Davies, B Barlogie, G Morgan
Journal: Leukemia (2015)

Over the last decade, new drugs have significantly changed the paradigm for treating multiple myeloma (MM), resulting in improved outcomes and reduced toxicity. However, many patients with MM relapse, and those who are refractory to or relapse after therapy with an immune-modulatory drug and a proteasome inhibitor have a dismal prognosis.1 Improving the outcome of relapsed and refractory MM is a significant clinical challenge. Importantly, in this respect, recently published data have established the frequent mutation of the RAS/mitogen-activated protein kinase (MAPK) pathway,2, 3, 4, 5 with mutations in NRAS, KRAS or BRAF being present in up to 50% of newly diagnosed MM cases. We routinely perform comprehensive genomic profiling using the FoundationOne Heme assay (Supplementary Methods). Review of these data shows the majority of the NRAS, KRAS and BRAF mutations occur in hotspots causing constitutive activation of the corresponding proteins. This makes the MAPK pathway a significant therapeutic target in MM.
Waist circumference and lung function among adolescents: The Pelotas 1993 birth cohort
Authors: Fernando C. Wehrmeister, Jeovany Martínez-Mesa, Pedro C. Hallal, Helen Gonçalves, Cora Araújo, Maria C.F. Assunção, Ricardo B. Noal, Rogelio Perez-Padilla, Ana Maria B. Menezes
Journal: European Respiratory Journal (2012)

Background: BMI is frequently used to evaluate obesity, but it is unable to assess fat distribution. Much attention has been given to abdominal fat measured by waist circumference (WC). Abdominal fat is a known risk factor for chronic diseases, but the impact of lung function among adolescents remains uncertain. Objective: To evaluate the association between WC and lung function parameters among adolescents. Methods: The original cohort comprised 5,249 hospital born children during the calendar year of 1993 in Pelotas, Brazil. In 2008-9, when participants were 15 years old, all cohort members were evaluated. WC was measured by trained interviewers and lung function tests were performed to obtain FVC and FEV1. Multiple linear regression models were performed and all analyses were stratified by sex. Results: 1,969 boys and 2,032 girls had data for spirometry and for WC. In the crude analyses we found a positive relationship between WC and FEV1 and FVC (liters) for both boys and girls. After adjusting for height, BMI, physical activity and wheezing in the past year, we found an inverse relationship between WC and FEV1 (β = -0.015 [95%CI -0.023; -0.008]), and FVC (β = -0.010 [95%CI -0.018; -0.001]) only for boys. For girls, the association was not significant. When we analyzed the predicted values, there was a significant association with WC (%FEV1, β = -0.413 [95%CI -0.619; -0.206]; %FVC β = -0.242 [95%CI -0.464; -0.020]) only for boys Conclusions: Increases in WC were associated with worse lung function parameters in Brazilian boys aged 15 years old. Improvement of lung health in adolescent can prevent lung diseases in adult life.
Challenging the two concepts in determining the appropriate pre‐discharge N‐terminal pro‐brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?
Authors: Susan Stienen, Khibar Salah, Luc W.M. Eurlings, Paulo Bettencourt, Joana M. Pimenta, Marco Metra, Antoni Bayes‐Genis, Valerio Verdiani, Luca Bettari, Valentina Lazzarini, Jan P. Tijssen, Yigal M. Pinto, Wouter E.M. Kok
Journal: European Journal of Heart Failure (2015)
Left ventricular dysfunction in patients with COPD: Inflammation and endothelial dysfunction
Authors: Natalia Kuzubova, Aleksei Gichkin, Ekatherina Surkova, Olga Titova
Journal: European Respiratory Journal (2013)

The aim of the study - to identify the role of systemic inflammation and endothelial dysfunction in the development of left ventricular dysfunction in patients with chronic obstructive pulmonary disease (COPD). Materials and methods. Endothelium-dependent vasodilatation of brachial artery (EDVD), echocardiography data of left and right heart chambers, the concentration of pro-inflammatory and anti-inflammatory cytokines and circulating immune complexes (CIC) in plasma were studied in 60 patients with moderate COPD. Results. COPD patients showed a reduction of left ventricular contractile activity compared to the control group. Reducing EDVD was found in 72% of patients with COPD. In the development of left ventricular failure involved a disorder of interventricular interaction. Correlation analysis of the relationship of molecular indicators of inflammatory activity and echocardiography data were identified: correlation between the concentration of the CIC and the pulmonary artery systolic pressure (PASP), between the level of IL-1β and PASP, between the concentration of IL-8 and the PASP. Conclusions. COPD patients at an early stage of the disease to detect violations of vasoactive endothelial function, an imbalance of pro- and anti- inflammatory cytokines, increasing the concentration of CIC. Developing systemic inflammation and endothelial dysfunction contribute not only to the formation of pulmonary hypertension and chronic cor pulmonale, but also the development of left ventricular failure.
Glutathione &lt;italic&gt;S&lt;/italic&gt;-Transferase Activity: Enhancement by Compounds Inhibiting Chemical Carcinogenesis and by Dietary Constituents&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: V L Sparnins, P L Venegas, L W Wattenberg
Journal: JNCI Journal of the National Cancer Institute (1982)

Benzyl isothiocyanate, β-naphthoflavone, coumarin, α-angelicalactone, disulfiram, indole-3-carbinol and indole-3-acetonitrile induced increased glutathione (GSH) S-transferase activity in the liver and small intestine in female ICR/Ha mice. All seven compounds are inhibitors of chemical carcinogenesis. In additional work, several dietary constituents increased GSH S-transferase activity. Consumption of diets containing dried powdered preparations of brussels sprouts, cabbage, coffee beans, or tea leaves resulted in increased GSH S-transferase activity. Mice fed an unrefined diet (Purina Rat Chow) had a higher GSH S-transferase activity than those fed a semipurified diet. The results of the present study indicated that the composition of the diet can alter the activity of an important enzyme system having the capacity to detoxify chemical carcinogens.
Airway cooling: stimulus specific modulation of airway responsiveness in the canine lung periphery
Authors: AN Freed, CE Stream
Journal: European Respiratory Journal (1991)

We used a wedged bronchoscope technique in conjunction with an in situ isolated perfused left lower lobe preparation in anesthetized dogs to examine cold-associated airway modulation of peripheral lung responses to dry airflow, hypocapnia, and aerosols of histamine and hypertonic NaCl. In this preparation, airway wall temperature was rapidly lowered by decreasing the temperature of blood perfusing the wedged sublobar segment. Cooling significantly attenuated responses to dry air, hypertonic NaCl aerosol, and hypocapnic challenge. In contrast, cooling did not affect peripheral lung responses to aerosolized histamine. Thus, cooling per se does not inhibit the responsiveness of smooth muscle. We conclude that, depending on the stimulus, cooling can modulate airway reactivity. We speculate that cooling attenuates hypocapnia, hypertonic aerosol, and dry air-induced bronchospasm via a cold induced reduction in neuronal activity or mediator production and release.
Involvement of asparatic acid racemization and isomerization in the pathogenesis of COPD
Authors: Rumi Koizumi, Masahito Ogasawara, Nobuhito Sasaki, Tatsuo Tanita, Yutaka Nakamura, Kohei Yamauchi
Journal: European Respiratory Journal (2013)

Background: Oxidative stress induces racemization and isomerization of asparatic acid such as a change from the L-form to D-form which causes a semi-permanent protein transformation.  Objectives:We hypothesized that proteins modified and damaged by oxidative stress including amino acid racemization and isomerization might obtain antigenicity as abnormal proteins resulting in immunological inflammation in the airways of COPD. To prove this hypothesis, we investigated abnormal proteins containing D-form aspartic acids in lung tissue from COPD patients.  Methods: Lung specimens surgically isolated from COPD patients were utilized to detect D-asparatic acid. To investigate exhaustively D-asparatic acid isomerization in the protein, we employed a paenidase I, D-asparatic asic specific endopeptidase, in combination with comparative two dimensional electrophoresis analysis. The endopeptidase sensitive proteins revealed decreased amounts of intensity in the proteins. The sensitive proteins were identified by mass spectrometry analysis. Furthermore, we studied the asparatic acid isomerization in vitro using a cell culture system under cigarette smoke exposure.  Results:In the proteins from COPD lungs, 4 isomerized proteins, Prohibitin, Peroxiredoxin-2, Glutathione S-transferase Pi, and serum amyloid p component, were detected significantly at 30-40% compared to 7% in control patients. Further, in the in vitro studies, cigarette smoke extracts increased the ratio of the isomerized proteins.  Concludion: Protein isomerization process occurred highly in the lung of COPD and the content of D-aspartic acid in the proteins of lung tissues from COPD patients was markedly higher than that in normal lungs.
Short-term therapy for acute myelogenous leukemia.
Authors: A Z Rohatiner, W M Gregory, R Bassan, M J Barnett, J Waxman, M A Richards, T S Ganesan, J Tucker, S T Malik, R Biruls
Journal: Journal of Clinical Oncology (1988)

Since 1978, 187 patients (age range, 15 to 59, median 44 years) have received short-term chemotherapy as part of three sequential open studies (B-IX, X, Xb) or a randomized clinical trial (B-XI). An intended six cycles of Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), cytarabine (ara-C), and thioguanine (TG) were administered with as short an intercycle time as possible. No further therapy was administered. Complete remission (CR) was achieved in 118 of 187 patients (63%). On univariate and multivariate analyses achievement of CR correlated adversely with a low serum albumin at presentation and an antecedent marrow disorder. Forty-five patients continue in first remission between 15 months and 8 1/2 years, no relapses being seen after 3 1/2 years (median follow-up, 3 1/2 years). The median duration of remission was 1 year. M3 morphology, a blast count less than 100 x 10(9)/L, and absence of hepatosplenomegaly correlated favorably with remission duration. There was no difference in duration of remission between patients receiving 3, 4, 5, or 6 cycles. The best results overall were achieved in patients under the age of 40, with 43% projected to remain free of disease at 5 years. Fifty patients remain alive between 17 months and 9 years, the predicted actuarial survival being 25% at 5 years.
Suppressed Murine Mammary Tumor Virus (MuMTV) Expression in RIII Female Mice Treated Neonatally With Goat Antiserum to MuMTV&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Asher Frensdorff, Abraham Wald
Journal: JNCI Journal of the National Cancer Institute (1978)

Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days).
Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression
Authors: Gopeshwar Narayan, Chandra Goparaju, Hugo Arias-Pulido, Andreas M Kaufmann, Achim Schneider, Matthias Dürst, Mahesh Mansukhani, Bhavana Pothuri, Vundavalli V Murty
Journal: Molecular Cancer (2006)

Abstract Background Cervical Cancer (CC) exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo). These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers. Results To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1 , SLIT2 , SLIT3 , ROBO1 , and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression. Conclusion Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i) play a role in CC development, (ii) further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii) form epigenetic signatures to identify precancerous lesions at risk to progression.
Biological Behavior Through Successive Transplant Generations of Transplantable Tumors Derived Originally From Primary Chemically Induced and Spontaneous Sources in Mice
Authors: Hilda Wexler, S. Kirby Orme, Alfred S. Ketcham
Journal: JNCI Journal of the National Cancer Institute (1968)

Extensive studies on the survival rates of tumor-bearing mice in three induced and two spontaneous tumors show that there is a variation in the growth rate of the primary tumor and in pulmonary and extrapulmonary metastases over a period of several transplant tumor generations. From its inception, each tumor has its own malignant pattern, as determined by its growth rate and distant metastases. In general, induced tumors are more malignant than spontaneous tumors on the basis of these two parameters. Results may differ, depending upon the age of the tumor selected. After a number of transplant tumor generations the tumor behavior is more predictable. The time it takes to reach this relatively constant pattern varies with the individual tumor. The virulence of a tumor can be determined in both tumor-bearing and amputated tumor mice. The present investigation revealed that surgery reduced the number of mice with metastases and the number of metastases in each mouse. Contrary to results of previous reports, we found that original carcinogen-induced tumors and spontaneously arising tumors do metastasize when the animals survive long enough for cells to shed from the original tumor.
The role of galactomannan in exhaled breath condensate in detecting pulmonary aspergillosis in patients with exacerbated COPD
Authors: Caterina Folisi, Laura Trovato, Raffaele Campisi, Salvatore Oliveri, Giuseppe Di Maria
Journal: European Respiratory Journal (2012)

Introduction:  Growing evidence suggests that patients with severe COPD are at a higher risk of pulmonary aspergillosis (PA), especially during an exacerbation. The levels of GM in exhaled breath condensate (EBC) might allow earlier diagnosis and extend the diagnostic yield of noninvasive mycological tests.   Objective:  Evaluate the role of GM in EBC for early diagnosis of PA in severe COPD patients at exacerbation.   Methods:  Serum and EBC were collected from 15 severe or very severe COPD patients at exacerbation and tested for GM using a Platelia®  Aspergillus  Ag test. Sera/EBC fluids with an index >0.5 were considered positive. Double diffusion in agarose gel (DD) for antibody response to  Aspergillus  was also determined.   Results:  Two patients had probable, 7 possible and 6 had no evidence of PA according to the criteria proposed by Bulpa. Serum positive GM assay was observed in two samples of the patients with probable PA and in one sample of two patients with possible PA. In patients with probable PA also serum precipitins was positive ( A. fumigatus ). EBC analysis yielded GM positive results (range, 0.8–7.5) in one patient with probable PA, in 2 patients with possible PA and in 2 patients without PA. In a patient with probable PA, positivity of the GM in EBC, preceded that of the serum of 4 days. GM in EBC was negative in 5 out of 7 cases with possible PA and in 5 out of 6 without PA. The sensitivity of GM in EBC was lower for the diagnosis of probable and possible PA compared to serum GM. However, considering the discordant results in serum and in EBC of four patients with possible PA we suggest that EBC GM levels can expand the diagnostic yield of PA.
Basic Fibroblast Growth Factor and Shiga Toxin–O157
Authors: Phillip I. Tarr
Journal: Journal of the American Society of Nephrology (2002)

The hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy that occurs in about 15% of children infected with Escherichia coli O157:H7 and in an unknown fraction of cases after infection with other Shiga toxin (Stx)–producing Escherichia coli (STEC). HUS is characterized by nonimmune
Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events
Authors: D. H. Solomon, G. W. Reed, J. M. Kremer, J. R. Curtis, M. E. Farkouh, L. R. Harrold, M. C. Hochberg, P. Tsao, J. D. Greenberg
Journal: Arthritis & Rheumatology (2015)

Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events.We studied patients with RA whose cases were followed in a longitudinal US-based registry. Time-averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person-years (95% confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted above, a 10-point reduction in the time-averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13-29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.Our findings showed that reduced time-averaged disease activity in RA is associated with fewer CV events.
Phase I Clinical Trial of Bendamustine and Bevacizumab for Patients With Advanced Cancer
Authors: Apostolia M. Tsimberidou, Alexandra M. Adamopoulos, Yang Ye, Sarina Piha-Paul, Filip Janku, Siqing Fu, David Hong, Gerald S. Falchook, Aung Naing, Jennifer Wheler, Adoneca Fortier, Razelle Kurzrock, Kenneth R. Hess
Journal: Journal of the National Comprehensive Cancer Network (2014)

Bendamustine, a cytotoxic alkylating agent, has shown promising results in solid tumors. An investigator-initiated phase I clinical trial of the anti-vascular endothelial growth factor agent bevacizumab and bendamustine was conducted in patients with advanced cancer, because the 2 drugs have different mechanisms of antitumor activity and nonoverlapping toxicity. Patients were treated with escalating doses of intravenous bendamustine (70, 80, 90, and 100 mg/m2; days 1 and 2) and intravenous bevacizumab (10 mg/kg; days 1 and 15). A conventional "3 + 3" study design was used. Forty-two patients were treated: 23 women and 19 men. The median age was 60 years. Patients had received a median of 4 prior therapies (range, 1-10). The most common cancer types were colorectal (n=9), head and neck (n= 8), non-small cell lung (n=6), and breast (n=5). Overall, 117 cycles were administered (median per patient, 2; range, 1-8). No dose-limiting toxicities were noted during the escalation phase. Therefore, the highest dose (level 4) of bendamustine (100 mg/m2) was used in the expansion phase. The most common toxicities were fatigue (n=22), nausea (n=14), anorexia (n=9), and thrombocytopenia (n=7). Of 38 patients who were evaluable for response, 23 (61%) had stable disease, including 2 (5.2%) who had stable disease for 6 months or more (1 with adenoid cystic carcinoma and 1 with non-small cell lung cancer). This regimen of bendamustine (100 mg/m2) and bevacizumab (10 mg/kg) was well tolerated and yielded disease stabilization in selected heavily pretreated patients with advanced cancer.