tbuckley/cabot-search huggingface dataset:
Criterion-related validity of field-based fitness tests in youth: a systematic review
Authors: J Castro-Piñero, E G Artero, V España-Romero, F B Ortega, M Sjöström, J Suni, J R Ruiz
Journal: British Journal of Sports Medicine (2009)

The objective of this systematic review was to comprehensively study the criterion-related validity of the existing field-based fitness tests used in children and adolescents. The studies were scored according to the number of subjects, description of the study population and statistical analysis. Each study was classified as high, low and very low quality. Three levels of evidence were constructed: strong evidence, when consistent findings were observed in three or more high quality studies; moderate evidence, when consistent findings were observed in two high quality studies; and limited evidence when consistency of findings and/or the number of studies did not achieve the criteria for moderate. The results of 73 studies (50 of high quality) addressing the criterion-related validity of field-based fitness tests in children and adolescents indicate the following: that there is strong evidence indicating that the 20 m shuttle run test is a valid test to estimate cardiorespiratory fitness, that the hand-grip strength test is a valid measure of musculoskeletal fitness, that skin fold thickness and body mass index are good estimates of body composition, and that waist circumference is a valid measure to estimate central body fat. Moderate evidence was found that the 1-mile run/walk test is a valid test to estimate cardiorespiratory fitness. A large number of other field-based fitness tests presented limited evidence, mainly due to a limited number of studies (one for each test). The results of the present systematic review should be interpreted with caution due to the substantial lack of consistency in reporting and designing the existing validity studies.
A comparative analysis of exome capture
Authors: Jennifer S Parla, Ivan Iossifov, Ian Grabill, Mona S Spector, Melissa Kramer, W Richard McCombie
Journal: Genome biology (2011)

Human exome resequencing using commercial target capture kits has been and is being used for sequencing large numbers of individuals to search for variants associated with various human diseases. We rigorously evaluated the capabilities of two solution exome capture kits. These analyses help clarify the strengths and limitations of those data as well as systematically identify variables that should be considered in the use of those data. Each exome kit performed well at capturing the targets they were designed to capture, which mainly corresponds to the consensus coding sequences (CCDS) annotations of the human genome. In addition, based on their respective targets, each capture kit coupled with high coverage Illumina sequencing produced highly accurate nucleotide calls. However, other databases, such as the Reference Sequence collection (RefSeq), define the exome more broadly, and so not surprisingly, the exome kits did not capture these additional regions. Commercial exome capture kits provide a very efficient way to sequence select areas of the genome at very high accuracy. Here we provide the data to help guide critical analyses of sequencing data derived from these products.
Reporting research in medical journals and newspapers
Authors: A. M Van Trigt, F. M Haaijer-Ruskamp, L. T W D. J.-V. Den Berg
Journal: BMJ (1995)

EDITOR,--Vikki Entwistle reports that British medical journalists base their stories on full research articles and not on the journals' press releases.1 In contrast to the journalists whom she interviewed, the respondents in a comparable study in the Netherlands said that they did not use the letters to the editor as a source of information because they are not peer reviewed.2 Entwistle, however, did not find many letters reported in newspaper articles. In our study we differentiated …
Nestin Is Expressed in the Basal/Myoepithelial Layer of the Mammary Gland and Is a Selective Marker of Basal Epithelial Breast Tumors
Authors: Hua Li, Pratima Cherukuri, Na Li, Victoria Cowling, Michael Spinella, Michael Cole, Andrew K. Godwin, Wendy Wells, James DiRenzo
Journal: Cancer Research (2007)

Abstract Transcriptional profiling has identified five breast cancer subtypes, of which the basal epithelial is most aggressive and correlates with poor prognosis. These tumors display a high degree of cellular heterogeneity and lack established molecular targets, such as estrogen receptor-α, progesterone receptor, and Her2 overexpression, indicating a need for definitive diagnostic markers. We present evidence that nestin, a previously described marker of regenerative cells in diverse tissues, is expressed in the regenerative compartment of the normal human mammary gland. Colocalization studies indicate two distinct populations of mammary epithelia that express nestin: one expressing cytokeratin 14 (CK14) and ΔN-p63 and another expressing desmin. Immunohistochemical analysis indicates that ΔN-p63 and nestin are coordinately expressed during pregnancy in the murine mammary gland. In the embryonal carcinoma cell line NT2/D1, ectopic ΔN-p63-α disrupts retinoic acid–induced differentiation, thereby preserving expression of nestin; however, small interfering RNA–mediated ablation of nestin is insufficient to promote differentiation, indicating that whereas nestin may identify cells within the regenerative compartment of the mammary gland, it is insufficient to block differentiation and preserve replicative capacity. Immunohistochemical analysis of basal epithelial breast tumors, including those shown to carry BRCA1 mutations, indicates robust expression of nestin and CK14, punctate expression of p63, and low to undetectable levels of desmin expression. Nestin was not detected in other breast cancer subtypes, indicating selectivity for basal epithelial breast tumors. These studies identify nestin as a selective marker of the basal breast cancer phenotype, which displays features of mammary progenitors. [Cancer Res 2007;67(2):501–10]
Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia.
Authors: G Schuler, G Schlierf, A Wirth, H P Mautner, H Scheurlen, M Thumm, H Roth, F Schwarz, M Kohlmeier, H C Mehmel
Journal: Circulation (1988)

The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.
Excision Repair Cross-Complementing Group 1 May Predict the Efficacy of Chemoradiation Therapy for Muscle-Invasive Bladder Cancer
Authors: Atsunari Kawashima, Masashi Nakayama, Yoichi Kakuta, Toyofumi Abe, Koji Hatano, Masatoshi Mukai, Akira Nagahara, Yasutomo Nakai, Daizo Oka, Hitoshi Takayama, Toshiaki Yoshioka, Yoshihiko Hoshida, Hiroaki Itatani, Kazuo Nishimura, Norio Nonomura
Journal: Clinical Cancer Research (2010)

Chemoradiation therapy (CRT) is now widely recognized as bladder-preserving therapy for muscle-invasive bladder cancer (MIBC). However, some patients who fail CRT may miss the chance to be cured by cystectomy. Therefore, it is important to select patients with MIBC who are expected to have a good response to CRT. Several reports indicate that the excision repair cross-complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and radiation therapy. In this study, we examined the correlation between ERCC1 and CRT in vitro and in vivo in bladder cancer.Bladder cancer cell lines T24, 5637, Cl8-2 (multidrug-resistant subline of T24), and CDDP10-3 (cisplatin-resistant subline of T24) were used for in vitro assays to measure ERCC1 expression level and growth inhibition with cisplatin or ionizing radiation (IR). We then examined by immunohistochemistry that whether ERCC1 nuclear staining correlates with the efficacy of CRT using cisplatin in 22 patients with MIBC.Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24. Cl8-2 and CDDP10-3 were more resistant to cisplatin or IR than was T24. Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of 8 positive cases did not have complete response to CRT, whereas 12 of 14 negative cases had complete response. Sensitivity and specificity were 75% and 85.7%, respectively (P = 0.008).Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC.
Compensatory Evolution in Response to a Novel RNA Polymerase: Orthologous Replacement of a Central Network Gene
Authors: J. Bull, R Springman, I. Molineux
Journal: Molecular Biology and Evolution (2007)

A bacteriophage genome was forced to evolve a new system of regulation by replacing its RNA polymerase (RNAP) gene, a central component of the phage developmental pathway, with that of a relative. The experiment used the obligate lytic phage T7 and the RNAP gene of phage T3. T7 RNAP uses 17 phage promoters, which are responsible for all middle and late gene expression, DNA replication, and progeny maturation, but the enzyme has known physical contacts with only 2 other phage proteins. T3 RNAP was supplied in trans by the bacterial host to a T7 genome lacking its own RNAP gene and the phage population was continually propagated on naive bacteria throughout the adaptation. Evolution of the T3 RNAP gene was thereby prevented, and selection was for the evolution of regulatory signals throughout the phage genome. T3 RNAP transcribes from T7 promoters only at low levels, but a single mutation in the promoter confers high expression, providing a ready mechanism for reevolution of gene expression in this system. When selected for rapid growth, fitness of the engineered phage evolved from a low of 5 doublings/h to 33 doublings/h, close to the expected maximum of 37 doublings/h. However, the experiment was terminated before it could be determined accurately that fitness had reached an obvious plateau, and it is not known whether further adaptation could have resulted in complete recovery of fitness. More than 30 mutations were observed in the evolved genome, but changes were found in only 9 of the 16 promoters, and several coding changes occurred in genes with no known contacts with the RNAP. Surprisingly, the T7 genome adapted to T3 RNAP also maintained high fitness when using T7 RNAP, suggesting that the extreme incompatibility of T7 elements with T3 RNAP is not an invariant property of divergence in these expression systems.
Chemokines in colitis: microRNA control
Authors: Ishan Roy, Christopher T Veldkamp, Brian F Volkman, Michael B Dwinell
Journal: Gut (2013)

Huang et al 1 identified and tested the role of a specific microRNA (miRNA) in the pathogenesis of IBD. The study of microRNAs is a burgeoning field within epigenetics. These small non-coding RNAs mediate translation-level repression of protein expression by binding to the 3′ -untranslated region of specific messenger RNA transcripts. In the innate and adaptive immune response, miRNAs play an important role in negative regulation of inflammatory conditions in the intestine. Inflammatory regulators such as IL-6, tumor necrosis factor (TNF) and toll-like receptors have been shown to induce miRNA expression in both acute and chronic inflammation. The roles for miRNAs in IBD are emerging from recent studies that compare miRNA expression in colonoscopic and peripheral blood draw biopsies from colitis patients with healthy individuals.2 Despite this, the vast majority of miRNAs identified in microarray analyses of colitis patients have yet to be investigated in experimental models of colitis or assigned specific mechanisms in the pathophysiology of human disease. In a novel approach, Huang et al 1 used array analyses to assay changes in microRNA expression from two different experimental models of colitis in order to map specific overlapping miRNA expression patterns, which were subsequently compared against analyses completed on human colitis patient specimens. These authors then continued their analyses to mechanistically determine that miR-141, a miRNA aberrantly expressed in both animal models of colitis and human patients, specifically inhibited expression of the β-isoform of CXCL12, a …
Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity
Authors: Giorgio Minotti, Pierantonio Menna, Emanuela Salvatorelli, Gaetano Cairo, Luca Gianni
Journal: Pharmacological Reviews (2004)

The clinical use of anthracyclines like doxorubicin and daunorubicin can be viewed as a sort of double-edged sword. On the one hand, anthracyclines play an undisputed key role in the treatment of many neoplastic diseases; on the other hand, chronic administration of anthracyclines induces cardiomyopathy and congestive heart failure usually refractory to common medications. Second-generation analogs like epirubicin or idarubicin exhibit improvements in their therapeutic index, but the risk of inducing cardiomyopathy is not abated. It is because of their janus behavior (activity in tumors vis-à-vis toxicity in cardiomyocytes) that anthracyclines continue to attract the interest of preclinical and clinical investigations despite their longer-than-40-year record of longevity. Here we review recent progresses that may serve as a framework for reappraising the activity and toxicity of anthracyclines on basic and clinical pharmacology grounds. We review 1) new aspects of anthracycline-induced DNA damage in cancer cells; 2) the role of iron and free radicals as causative factors of apoptosis or other forms of cardiac damage; 3) molecular mechanisms of cardiotoxic synergism between anthracyclines and other anticancer agents; 4) the pharmacologic rationale and clinical recommendations for using cardioprotectants while not interfering with tumor response; 5) the development of tumor-targeted anthracycline formulations; and 6) the designing of third-generation analogs and their assessment in preclinical or clinical settings. An overview of these issues confirms that anthracyclines remain "evergreen" drugs with broad clinical indications but have still an improvable therapeutic index.
Assessing horizontal transfer of nifHDK genes in eubacteria: nucleotide sequence of nifK from Frankia strain HFPCcI3.
Authors: A. M. Hirsch, H. I. McKhann, A. Reddy, J. Liao, Y. Fang, C. R. Marshall
Journal: Molecular Biology and Evolution (1995)

The structural genes for nitrogenase, nifK, nifD, and nifH, are crucial for nitrogen fixation. Previous phylogenetic analysis of the amino acid sequence of nifH suggested that this gene had been horizontally transferred from a proteobacterium to the gram-positive/cyanobacterial clade, although the confounding effects of paralogous comparisons made interpretation of the data difficult. An additional test of nif gene horizontal transfer using nifD was made, but the NifD phylogeny lacked resolution. Here nif gene phylogeny is addressed with a phylogenetic analysis of a third and longer nif gene, nifK. As part of the study, the nifK gene of the key taxon Frankia was sequenced. Parsimony and some distance analyses of the nifK amino acid sequences provide support for vertical descent of nifK, but other distance trees provide support for the lateral transfer of the gene. Bootstrap support was found for both hypotheses in all trees; the nifK data do not definitively favor one or the other hypothesis. A parsimony analysis of NifH provides support for horizontal transfer in accord with previous reports, although bootstrap analysis also shows some support for vertical descent of the orthologous nifH genes. A wider sampling of taxa and more sophisticated methods of phylogenetic inference are needed to understand the evolution of nif genes. The nif genes may also be powerful phylogenetic tools. If nifK evolved by vertical descent, it provides strong evidence that the cyanobacteria and proteobacteria are sister groups to the exclusion of the firmicutes, whereas 16S rRNA sequences are unable to resolve the relationships of these three major eubacterial lineages.
Antipsychotic Drugs, Neurotransmitters, and Schizophrenia
Authors: ARVID CARLSSON
Journal: American Journal of Psychiatry (1978)

Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the mental and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or dopa may lead to a disturbance mimicking paranoid schizophrenia lends further support for a key role of dopamine in mental functions. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, amino acid, or peptide transmitters in schizophrenia cannot be disregarded.
Gene Transfer to Neurons Using Herpes Simplex Virus-Based Vectors
Authors: D J Fink, N A DeLuca, W F Goins, J C Glorioso
Journal: Annual Review of Neuroscience (1996)

One important outgrowth of molecular medicine is the development of technologies for the transfer of therapeutic genes to cells in culture and tissues in vivo, which promises to revolutionize both experimental biomedical science and the clinical practice of medicine. Fundamental obstacles must still be overcome to create safe and efficient gene delivery vectors specifically designed for individual tissue types, and special strategies will be required for direct in vivo gene transfer to neurons because these cells are postmitotic and cannot be removed for transduction. Herpes simplex virus type 1 (HSV-1), a neurotropic virus that naturally establishes a latent state in neurons, has many unique features that make it suitable as a gene transfer vector for the nervous system. In this review we describe the molecular biology of HSV-1, strategies for reducing potential pathogenesis of the recombinant vector, and methods for expressing transgenes from the vector genome. Gene transfer experiments using recombinant HSV-1-based vectors and defective HSV-1 vectors (amplicons) for gene transfer are also described and evaluated in terms of efficiency and safety.
Pharmacokinetics of Digoxin: Interpreting Bioavailability
Authors: N. Sanchez, L. B. Sheiner, H. Halkin, K. L. Melmon
Journal: BMJ (1973)

Three subjects were first given a digoxin tablet in the fasting state and subsequently received the same formulation in the fed state, to simulate a spurious oral bioavailability difference. As expected, when measured by peak serum digoxin concentration as well as by area under the serum digoxin concentration-time curve the bioavailability of digoxin appeared to be higher in the fasting state than in the fed state. However, when measured by cumulative five-day urinary excretion of digoxin bioavailability was identical in both conditions.This simple experiment illustrates the fact that the estimation of bioavailability is subject to considerable methodological error, of which the clinician must be aware when evaluating reports on drug bioavailability in general and of digoxin in particular.
Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis
Authors: J. I. Abu
Journal: Human Reproduction Update (2000)

The lipoxygenase products (leukotrienes) have been demonstrated in many mammalian tissues including humans. They are widely distributed in the lungs, gut, uterus, kidneys, skin, heart and the liver. Their roles as mediators of inflammation have made them therapeutic targets. Significant amounts of leukotrienes have been demonstrated in the endometrium of women with primary dysmenorrhoea who do not respond to treatment with anti-prostaglandins. Also, in endometriosis, cytokines, which can initiate the cascade for the biosynthesis of leukotrienes, have been shown to be elevated. It is estimated that 10-30% of patients with painful periods fail to respond to prostaglandin (PG) synthetase inhibitors. Of adult females approximately 40% have painful menstruation and 10% of these are incapacitated for 1-3 days per month, and approximately 10% of women aged between 15-45 years suffer from endometriosis, which is a significant cause of infertility. Leukotriene receptor antagonists have recently been licensed for the treatment of asthma in the UK. In this review, we present the case for the potential use of these products in the management of primary dysmenorrhoea (especially in patients who are not responding to the traditional treatment using PG synthetase inhibitors) and possibly also in cases of endometriosis.
Fluticasone Inhibits But Does Not Reverse Allergen-Induced Structural Airway Changes
Authors: NELE J. VANACKER, ELS PALMANS, JOHAN C. KIPS, ROMAIN A. PAUWELS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized BN rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.