tbuckley/cabot-search huggingface dataset:
Consensus recommendations on training and competing in the heat
Authors: S Racinais, J M Alonso, A J Coutts, A D Flouris, O Girard, J González-Alonso, C Hausswirth, O Jay, J K W Lee, N Mitchell, G P Nassis, L Nybo, B M Pluim, B Roelands, M N Sawka, J Wingo, J D Périard
Journal: British Journal of Sports Medicine (2015)

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimise performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimise performance is to heat acclimatise. Heat acclimatisation should comprise repeated exercise-heat exposures over 1–2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimise dehydration during exercise. Following the development of commercial cooling systems (eg, cooling-vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organisers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimising the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events, for hydration and body cooling opportunities, when competitions are held in the heat.
Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis
Authors: Xiaojun Zhao, Barbara A. Weir, Thomas LaFramboise, Ming Lin, Rameen Beroukhim, Levi Garraway, Javad Beheshti, Jeffrey C. Lee, Katsuhiko Naoki, William G. Richards, David Sugarbaker, Fei Chen, Mark A. Rubin, Pasi A. Jänne, Luc Girard, John Minna, David Christiani, Cheng Li, William R. Sellers, Matthew Meyerson
Journal: Cancer Research (2005)

Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing approximately 115,000 single nucleotide polymorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the PTPRD locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. High-level amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified high-level amplification of EGFR in three NSCLC specimens, FGFR1 in two specimens and ERBB2 and MET in one specimen each. EGFR amplification was shown to be independent of kinase domain mutational status.
MIG-7 Controls COX-2/PGE2-Mediated Lung Cancer Metastasis
Authors: Ming-Yi Ho, Shu-Mei Liang, Shao-Wen Hung, Chi-Ming Liang
Journal: Cancer Research (2012)

Abstract More effective treatments for metastatic lung cancer remain a pressing clinical need. In this study, we identified migration inducting gene-7 (MIG-7) protein as critical for COX-2/prostaglandin E2 (PGE2)- and Akt/GSK-3β-dependent tumor invasion/metastasis. COX-2/PGE2 activated EP4 to enhance Akt and GSK-3β phosphorylation and β-catenin/T-cell factor/lymphoid enhancer factor signaling leading to MIG-7 upregulation. RNAi-mediated attenuation of MIG-7 blocked COX-2/PGE2- and Akt/GSK-3β-mediated migration/invasion effects. Furthermore, MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK-3β phosphorylation and cancer-cell migration/invasion. Cancer cells overexpressing MIG-7 exhibited increased expression of ZEB-1 and Twist in parallel with epithelial–mesenchymal transition, metastasis and cancer lethality. MIG-7 protein level positively correlated with advanced stages of human lung cancers. MIG-7 thus offers a theranostic target for cancer metastases arising from aberrant activation of the cellular COX-2/PGE2 and Akt/GSK-3β signaling pathways. Cancer Res; 73(1); 439–49. ©2012 AACR.
Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients
Authors: Fahd Al-Mulla, Suzanne Hagan, Abdulla I. Behbehani, Milad S. Bitar, Shirley S. George, James J. Going, Jorge J. Curto García, Lucy Scott, Nicky Fyfe, Graeme I. Murray, Walter Kolch
Journal: Journal of Clinical Oncology (2006)

Raf kinase inhibitor protein (RKIP) inhibits the Raf and nuclear factor kappa B signaling pathways, and suppresses metastasis in animal models. We examined whether RKIP expression in primary colorectal cancers (CRCs) correlates with the risk of metastasis and overall survival.RKIP expression was examined immunohistochemically in three separate cohorts: a tissue microarray containing 276 samples from human tumors and normal tissues, and retrospective studies of 268 CRC patients and 65 early-stage CRCs. Overall and metastasis-free survival rates were measured.RKIP was expressed in normal epithelia but was reduced in metastatic tumors. RKIP expression in primary CRC was an independent prognostic marker for survival using multivariate Cox regression analysis (hazard ratio, 2.808; 95% CI, 1.58 to 4.96; P = .0002), independent of Dukes' stage. Patients with Dukes' C RKIP-positive tumors had similar 5-year survival rates as early-stage patients if tumors had equivalent RKIP expression levels. An independent study of early-stage CRCs confirmed that reduced RKIP expression predicted metastatic recurrence and reduced disease-free survival (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). RKIP expression was independent of sex, age, mitotic index, lymphatic and vascular invasion, depth of invasion, and tumor site, but correlated positively with apoptotic index (P = .024). Weak or loss of RKIP expression was the most significant and independent prognostic marker using a multivariate regression equation (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003).RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse.
Regulation of large cerebral arteries and cerebral microvascular pressure.
Authors: F M Faraci, D D Heistad
Journal: Circulation Research (1990)

Resistance of large arteries appears to be greater in the cerebral circulation than in other vascular beds. Large arteries contribute importantly to total cerebral vascular resistance and are major determinants of local microvascular pressure. Recent studies have shown that resistance of large arteries and cerebral microvascular pressure are affected by several physiological stimuli, including changes in systemic blood pressure, increases in cerebral metabolism, activity of sympathetic nerves, and humoral stimuli such as circulating vasopressin and angiotensin. Stimuli such as sympathetic stimulation and vasopressin produce selective responses of large arteries and, thereby, regulate microvascular pressure without a significant change in cerebral blood flow. These findings lead to the new hypothesis that the brain may be sensitive to changes in cerebral microvascular pressure, resulting in activation of compensatory neurohumoral mechanisms. Important changes occur in large cerebral arteries under pathophysiological conditions. Chronic hypertension increases resistance of large cerebral arteries, which protects the microcirculation against hypertension. Atherosclerosis potentiates constrictor responses of large cerebral arteries to serotonin and thromboxane, which may contribute to vasospasm and transient ischemic attacks.
Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis.
Authors: K Steinmann-Niggli, R Ziswiler, M Küng, H P Marti
Journal: Journal of the American Society of Nephrology (1998)

There is accumulating evidence that matrix metallo-proteinases (MMP) play a prominent role in glomerular inflammatory diseases. The aim of the present study was to determine the anti-inflammatory effects of the synthetic MMP inhibitor BB-1101 in acute anti-Thy1.1 nephritis. Sixty-three male Wistar rats were studied: healthy rats (n = 9), treated healthy rats (n = 9), nephritic rats (n = 18), and treated nephritic rats (n = 27). BB-1101 therapy (30 mg/kg body wt per d) of nephritic animals was initiated either 2 d before (n = 18) or 2 d after (n = 9) disease induction. Renal histology was analyzed 11 d after induction of the nephritis, at the peak of MMP-2 production and total glomerular cellularity. Pretreatment of nephritic rats by BB-1101 resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, extracellular matrix deposition, and size of glomerular cross-sections. These beneficial effects were less pronounced, but in part still significant, in animals treated by BB-1101 after induction of anti-Thy1.1 nephritis. Proteinuria, expressed as area under the curve of the protein:creatinine ratio versus time, was clearly decreased in both groups of treated nephritic rats. Healthy control rats were not affected by MMP inhibitor treatment. In summary, the present study demonstrates for the first time in vivo that mesangial cell proliferation can be effectively suppressed by MMP inhibition. Thus, MMP inhibition by synthetic compounds may represent a new approach to the therapy of mesangial cell-mediated forms of glomerulonephritis.
Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial
Authors: Richard B Frobell, Harald P Roos, Ewa M Roos, Frank W Roemer, Jonas Ranstam, L Stefan Lohmander
Journal: British Journal of Sports Medicine (2015)

STUDY QUESTION In young active adults with an acute anterior cruciate ligament (ACL) rupture, do patient reported or radiographic outcomes after five years differ between those treated with rehabilitation plus early ACL reconstruction and those treated with rehabilitation and optional delayed ACL reconstruction? SUMMARY ANSWER At five years, patients assigned to rehabilitation plus early ACL reconstruction did not differ significantly in patient reported or radiographic outcomes from those assigned to initial rehabilitation with the option of having a later reconstruction if needed. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The relative efficacy of surgical reconstruction and rehabilitation for short and long term outcomes of ACL rupture is debated. Clinicians and young active adult patients should consider rehabilitation as a primary treatment option following an acute ACL tear.
Hepatitis B Virus Infection and Hepatocellular Carcinoma Among Parous Taiwanese Women: Nationwide Cohort Study
Authors: Chyng-Wen Fwu, Yin-Chu Chien, Gregory D. Kirk, Kenrad E. Nelson, San-Lin You, Hsu-Sung Kuo, Manning Feinleib, Chien-Jen Chen
Journal: JNCI Journal of the National Cancer Institute (2009)

Few long-term studies of hepatitis B virus (HBV) infection and hepatocellular carcinoma have focused on women. We used a nationwide cohort of reproductive-aged Taiwanese women to study relationships of HBV infection and parity with hepatocellular carcinoma risk.Prenatal test results were available for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in the National Hepatitis B Vaccination Registry from 1 782 401 pregnant women tested from October 1, 1983, through March 31, 2000. Data from the 306 women who were diagnosed with hepatocellular carcinoma were ascertained during 15 901 722 person-years of follow-up through linkage with National Cancer Registry and National Death Certification Registry. We used Cox proportional hazards models to investigate the association of age and reproductive and serological parameters with the risk of hepatocellular carcinoma.Incidence rates for hepatocellular carcinoma were 0.55, 7.91, and 8.76 per 100 000 person-years among women who were HBsAg negative (ie, noncarriers), HBsAg positive plus HBeAg negative, and HBsAg positive plus HBeAg positive, respectively (compared with noncarriers, for HBsAg-positive and HBeAg-positive women, age-adjusted hazard ratio [HR] for developing hepatocellular carcinoma = 17.31, 95% confidence interval [CI] = 12.08 to 24.81; and for HBsAg-negative plus HBeAg-positive women, HR = 13.94, 95% CI = 10.34 to 18.79). Incidence rates were 0.39, 3.10, and 9.01 per 100 000 person-years, respectively, among persistent noncarriers, HBsAg-serocleared carriers, and persistent HBsAg carriers (compared with noncarriers, for HBsAg-serocleared carriers, age-adjusted HR = 7.95, 95% CI = 3.50 to 18.04; and for HBsAg persistence, HR = 23.13, 95% CI = 14.23 to 37.61). Incidence rates were 2.04, 1.55, and 1.66 per 100 000 person-years for women who had one, two, or three or more children, respectively (compared with one child, for two children, age- and HBsAg-adjusted HR = 0.68, 95% CI = 0.50 to 0.93; and for three or more children, HR = 0.63, 95% CI = 0.42 to 0.92).The risk for hepatocellular carcinoma was statistically significantly higher among women with chronic or active HBV infections and among those with persistent HBV infection or who underwent HBsAg seroclearance during follow-up than among HBV-unexposed women. This risk decreased as parity increased, independent of HBsAg status and age.
Community participation: lessons for maternal, newborn, and child health
Authors: Mikey Rosato, Glenn Laverack, Lisa Howard Grabman, Prasanta Tripathy, Nirmala Nair, Charles Mwansambo, Kishwar Azad, Joanna Morrison, Zulfiqar Bhutta, Henry Perry, Susan Rifkin, Anthony Costello
Journal: The Lancet (2008)
Cyclosporin as a treatment for interstitial lung disease of unknown aetiology.
Authors: J A Moolman, P G Bardin, D J Rossouw, J R Joubert
Journal: Thorax (1991)

Ten patients with progressive, symptomatic interstitial lung disease of unknown aetiology who were treated with cyclosporin A were reviewed. Five had clinical and histopathological features of cryptogenic fibrosing alveolitis and five a progressive restrictive lung disease characterised by interstitial infiltration with lymphocytes and minimal fibrosis, which could not be classified precisely. Three patients with lymphocytic infiltration showed a response to initial treatment with cyclosporin A alone at high dosage, but toxicity precluded further treatment. All 10 patients then received low doses of cyclosporin A and prednisone. Three of the patients with cryptogenic fibrosing alveolitis and all five patients with lymphocytic infiltration responded with a reduction in dyspnoea or an increase in vital capacity, or both; cyclosporin A appeared to be effective, or at least to have a corticosteroid potentiating effect. A high incidence of side effects occurred, though these do not necessarily prohibit the long term use of cyclosporin A when it is indicated clinically. Cyclosporin A may be effective in the treatment of interstitial lung disease of unknown aetiology. Further studies are required to determine the long term outcome of treatment.
Alteration in the rheologic properties of plasmodium knowlesi-infected red cells. A possible mechanism for capillary obstruction
Authors: Louis H. Miller, Shunichi Usami, Shu Chien
Journal: Journal of Clinical Investigation (1971)

Red cells parasitized by Plasmodium knowlesi concentrate within the microcirculation of many organs including cerebral capillaries in rhesus monkeys. The possibility that P. knowlesi could alter the rheologic properties of red cells so that they are trapped within capillaries was investigated in the present study. The viscosity of P. knowlesi-infected red cells suspended in Ringer's solution was increased at all shear rates at hematocrits above 30%. At moderate parasitemia the resistance to flow through 5 mu polycarbonate sieves was increased; at high parasitemia the pores were obstructed. Mature trophozoites caused more obstruction than young trophozoites (rings) at any given level of parasitemia. The reduction of deformability of red cells infected by schizonts of P. knowlesi was further demonstrated by their exclusion from rouleaux in a plasma suspension. Therefore, the red cells infected by P. knowlesi become less deformable, and this reduction in red cell deformability may explain the obstruction of cerebral capillaries.
NOS3 Polymorphisms Are Associated With Arterial Stiffness in Children With Type 1 Diabetes
Authors: Issam Zineh, Amber L. Beitelshees, Michael J. Haller
Journal: Diabetes Care (2007)

OBJECTIVE—Type 1 diabetes is associated with endothelial dysfunction, arterial stiffness, and an increased risk of cardiovascular disease (CVD) events. We previously demonstrated increased arterial stiffness in children with type 1 diabetes compared with control subjects. However, traditional CVD risk factors did not explain the difference in arterial stiffness. Furthermore, children with type 1 diabetes displayed notable within-group variation in arterial stiffness. We hypothesized that polymorphisms in the NOS3 gene may be associated with the differences seen in arterial stiffness within the population of children with type 1 diabetes. RESEARCH DESIGN AND METHODS—Thirty-six consecutively enrolled subjects aged 10–21 years with type 1 diabetes were studied. Subjects underwent radial tonometry in a fasting state. A corrected augmentation index (AI75) was the primary measure of arterial stiffness. Genotypes were determined for the NOS3 −786T→C and Glu298→Asp polymorphisms by pyrosequencing. AI75 values by genotype groups were compared by ANOVA and multivariate analysis. RESULTS—Median (interquartile range) AI75 values for −786TT and −786C carriers were −3.5 (−8.8 to 2.3) and 11.0 (6.0 to 14.4), respectively (P = 0.01); AI75 values for Glu298Glu patients and Asp298 carriers were 2.3 (−4.0 to 13.0) and 7.3 (−2.0 to 11.5), respectively (P = 0.59). In univariate analysis, age, sex, BMI percentile, and −786T→C genotype were significantly associated with AI75. The multivariate model, which included these four variables, was significantly associated with AI75 (P = 0.002, R2 = 0.40). CONCLUSIONS—This is the first reported association between −786T→C and arterial stiffness in type 1 diabetes. Larger studies are needed to confirm this observation for potential translation to risk assessment.
Gene Expression Profiling in Breast Cancer: Understanding the Molecular Basis of Histologic Grade To Improve Prognosis
Authors: Christos Sotiriou, Pratyaksha Wirapati, Sherene Loi, Adrian Harris, Steve Fox, Johanna Smeds, Hans Nordgren, Pierre Farmer, Viviane Praz, Benjamin Haibe-Kains, Christine Desmedt, Denis Larsimont, Fatima Cardoso, Hans Peterse, Dimitry Nuyten, Marc Buyse, Marc J. Van de Vijver, Jonas Bergh, Martine Piccart, Mauro Delorenzi
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%–60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. Methods: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)–positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan–Meier analysis. All statistical tests were two-sided. Results: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1–3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P <.001, log-rank test). Conclusions: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.
Modifications of myocardial Na+,K+-ATPase isoforms and Na+/Ca2+ exchanger in aldosterone/salt-induced hypertension in guinea pigs
Authors: Juan Fernando Ramñrez-Gil, Pascal Trouvé, Nathalie Mougenot, Alain Carayon, Philippe Lechat, Danièle Charlemagne
Journal: Cardiovascular Research (1998)

The aim of this study was to determine whether changes in cardiac Na+,K(+)-ATPase subunits and Na+/Ca2+ exchanger expression are regulated in aldosterone-salt hypertensive guinea pigs.Guinea pigs (GP) were unilaterally nephrectomized and randomized into three groups (aldosterone-salt; control-salt; control). After 90 days of treatment, echocardiographic M-mode assessment and right carotid arterial catheterization were performed in vivo, and plasma hormones and electrolytes were measured. mRNA and protein levels were studied by Northern and Western blot analysis.Aldosterone-salt treatment induced, (1) arterial hypertension (+40%) and LV hypertrophy (+60%) without altering LV-fractional shortening, (2) an increase in plasma norepinephrine levels (+262%) and suppression of renin activity. Northern blot analysis showed the presence of the mRNA encoding the three alpha isoforms and the beta 1 subunit of Na+,K(+)-ATPase in GP myocardium. In the aldosterone-salt group, levels of alpha 1 and beta 1 mRNAs were unchanged. alpha 2 mRNA was increased in both ventricles, whereas alpha 3 mRNA was increased in hypertrophied LV only. Furthermore, levels of the Na+/Ca2+ exchanger mRNA were decreased in both ventricles. At protein level, the two major transcripts (alpha 1 and alpha 2) were detected but alpha 3 isoform was not. Parallel changes in protein and mRNA accumulation of alpha 1 and alpha 2 isoforms were observed in hypertrophied LV.These results show that alpha 1 and alpha 2 isoforms are expressed in GP heart and that they are independently regulated in aldosterone-salt hypertension. Like the alpha 1 isoform in renal tissue, alpha 2 isoform is the main target of aldosterone-salt. Reciprocal expression of the Na+/Ca2+ exchanger and Na+,K(+)-ATPase suggests an adaptational mechanism which maintains an appropriate sodium gradient and calcium concentration in hypertensive myocardium.