tbuckley/cabot-search huggingface dataset:
The financial cost of hamstring strain injuries in the Australian Football League
Authors: Jack Hickey, Anthony J Shield, Morgan D Williams, David A Opar
Journal: British Journal of Sports Medicine (2013)

<h3>Background</h3> Hamstring strain injuries (HSIs) have remained the most prevalent injury in the Australian Football League (AFL) over the past 21 regular seasons. The effect of HSIs in sports is often expressed as regular season games missed due to injury. However, the financial cost of athletes missing games due to injury has not been investigated. The aim of this report is to estimate the financial cost of games missed due to HSIs in the AFL. <h3>Method</h3> Data were collected using publicly available information from the AFL9s injury report and the official AFL annual report for the past 10 competitive AFL seasons. Average athlete salary and injury epidemiology data were used to determine the average yearly financial cost of HSIs for AFL clubs and the average financial cost of a single HSI over this time period. <h3>Results</h3> Across the observed period, average yearly financial cost of HSIs per club increased by 71% compared with a 43% increase in average yearly athlete salary. Over the same time period the average financial cost of a single HSI increased by 56% from $A25 603 in 2003 to $A40 021 in 2012, despite little change in the HSI rates during the period. <h3>Conclusions</h3> The observed increased financial cost of HSIs was ultimately explained by the failure of teams to decrease HSI rates, but coupled with increases in athlete salaries over the past 10 season. The information presented in this report highlights the financial cost of HSIs and other sporting injuries, raising greater awareness and the need for further funding for research into injury prevention strategies to maximise economical return for investment in athletes.
A clash of competing metaphors
Authors: Michael Bradie
Journal: Behavioral and Brain Sciences (1999)

Metaphors have three important functions in scientific discourse: heuristic, rhetorical, and epistemic. I argue that, contrary to prevailing opinion, metaphors are indispensable components of scientific methodology as well as scientific communication. Insofar as the choice of metaphors reflects ideological commitments, all science is ideological. The philosophically vexed question is how to characterize the sense in which science is not merely ideological.
Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16
Authors: P. J. Kausalya
Journal: Journal of Clinical Investigation (2006)

Claudin-16 (Cldn16) is selectively expressed at tight junctions (TJs) of renal epithelial cells of the thick ascending limb of Henle’s loop, where it plays a central role in the reabsorption of divalent cations. Over 20 different mutations in the CLDN16 gene have been identified in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), a disease of excessive renal Mg2+ and Ca2+ excretion. Here we show that disease-causing mutations can lead to the intracellular retention of Cldn16 or affect its capacity to facilitate paracellular Mg2+ transport. Nine of the 21 Cldn16 mutants we characterized were retained in the endoplasmic reticulum, where they underwent proteasomal degradation. Three mutants accumulated in the Golgi complex. Two mutants were efficiently delivered to lysosomes, one via clathrin-mediated endocytosis following transport to the cell surface and the other without appearing on the plasma membrane. The remaining 7 mutants localized to TJs, and 4 were found to be defective in paracellular Mg2+ transport. We demonstrate that pharmacological chaperones rescued surface expression of several retained Cldn16 mutants. We conclude that FHHNC can result from mutations in Cldn16 that affect intracellular trafficking or paracellular Mg2+ permeability. Knowledge of the molecular defects associated with disease-causing Cldn16 mutations may open new venues for therapeutic intervention.
Lung Endothelium Targeting for Pulmonary Embolism Thrombolysis
Authors: Bi-Sen Ding, Ying-Jiang Zhou, Xin-Yuan Chen, Jing Zhang, Pei-Xiang Zhang, Zi-Yong Sun, Xiang-Yang Tan, Jian-Ning Liu
Journal: Circulation (2003)

Pulmonary embolism occurs frequently in hospitalized patients. Thrombolytic therapy, currently used as the major treatment, has often been associated with severe bleeding complications and has thereby been life-threatening. We have developed a novel therapeutic method based on our newly created pulmonary endothelium-specific antibody.We isolated membrane proteins of rat pulmonary vascular luminal endothelium and obtained a monoclonal antibody, RE8F5, which antigen was uniquely expressed by the pulmonary capillary endothelium. In vivo biodistribution showed that RE8F5 and its urokinase conjugate were rapidly and specifically accumulated in lung. Urokinase and the conjugate were compared in rats with pulmonary, hepatic, and lower-limb embolus. In a pulmonary embolus model, the conjugate exhibited 12-fold enhanced thrombolytic potency over urokinase, whereas plasma fibrinogen and bleeding time were unaffected. In 2 other models, no significant thrombolysis was induced by the conjugate. In contrast, thrombolysis by urokinase was found to be comparable to the pulmonary embolus model. In addition, urokinase caused significant consumption of fibrinogen in all experiments.These data show that urokinase equipped with lung endothelium-specific antibody is an ideal treatment for pulmonary embolism, with a high efficacy of thrombolysis and low risk of bleeding.
Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness
Authors: B A Biggee
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Oral glucosamine preparations are widely used as a treatment for osteoarthritis, purportedly functioning by a variety of mechanisms suggested by results of in vitro experiments, and generally using glucosamine concentrations well in excess of 100 μmol/l. <b>Objective:</b> To use high performance liquid chromatography with a high sensitivity Metrohm-Peak instrument for pulsed amperometric measurement of human serum glucosamine; a detection limit of 0.5 μmol/l at 1:10 serum dilution allowed measurement of low levels of glucosamine in human serum, which previously has not been possible. <b>Methods:</b> Eighteen subjects with osteoarthritis were given 1500 mg of commercial glucosamine sulphate after an overnight fast, and serum was then obtained at baseline and every 15–30 minutes over 3 hours, and additionally, from two subjects at 5 and 8 hours. Urine samples were collected at baseline and 3 hours after ingestion from three subjects. <b>Results:</b> Baseline glucosamine was below the detection limit of 0.5 μmol/l for all subjects, but after ingestion, glucosamine was detected in 17/18 subjects, beginning to rise at 30–45 minutes to a maximum at 90–180 minutes, with a range of 1.9–11.5 μmol/l (0.34–2 μg/ml). <b>Conclusion:</b> This maximum concentration of 11.5 μmol/l has previously been shown to contribute less than 2% of the galactosamine incorporated into chondroitin sulphate in incubations of glucosamine with cultured human chondrocytes, and is a much lower concentration than the glucosamine concentrations claimed by other investigators to have various significant in vitro effects. This raises questions about current biological rationales for glucosamine use that were based on in vitro effects of glucosamine at much higher concentrations.
Multiple Comparisons of Log-Likelihoods with Applications to Phylogenetic Inference
Authors: H. Shimodaira, M. Hasegawa
Journal: Molecular Biology and Evolution (1999)

The maximum-likelihood method for inferring mo-lecular phylogeny (Felsenstein 1981) is being widelyused. The probabilistic model for generating the molec-ular sequences is speciﬁed by the substitution processand the tree topology. The parameters for the substitu-tion process and the branch lengths are estimated bymaximizing the likelihood, and then the tree topology isestimated by maximizing the maximized likelihood. Toobtain the conﬁdence limit of the topology, the test ofKishino and Hasegawa (1989), referred to as the KHtest, is often used in practice. The same idea that is thebasis for the KH test is also found in the statistical lit-erature (Linhart 1988; Vuong 1989). The KH test wasdesigned for comparing two topologies but is often usedfor comparing many topologies. This use of the KH testleads to overconﬁdence for a wrong tree, because thesampling error due to the selection of the topology isoverlooked in it. In this note, we present a modiﬁcationof the KH test to take into account a multiplicity oftestings.Let a index the topologies and L
Mechanism of calcium channel block by D600 in single smooth muscle cells from rabbit ear artery.
Authors: S Hering, T B Bolton, D J Beech, S P Lim
Journal: Circulation Research (1989)

This study investigated the action of the calcium antagonist D600 on calcium channel currents recorded in high barium solution from single, enzymatically isolated smooth muscle cells from the rabbit ear artery using the whole cell configuration of the patch-clamp technique. D600 (1-100 microM) was applied by path perfusion or by a new technique that allowed a concentration jump during the current. Application of D600 at rest (holding potential, -60 mV) did not alter the peak inward current elicited on depolarization, but the activation of the channels led to a marked block and an acceleration of the current decay. The mechanism of block of calcium channels by D600 was studied by using pulse protocols with different pulse length and different interpulse intervals. The results were consistent with the hypothesis that D600 has a low affinity for the calcium channels in the resting state and that they have to pass to the open state before the drug affects the calcium channel current. A fast onset of the calcium channel block by D600 (time constant, 502 msec) could be shown by rapid application of D600 during the sustained current component of the barium inward current. However, experiments did not definitely distinguish whether binding occurred to the open or to the inactivated state (although there was some evidence of a long-lasting binding to an inactivated state).
Longitudinal Modeling of Age-Related Memory Decline and the<i>APOE</i>ε4 Effect
Authors: Richard J. Caselli, Amylou C. Dueck, David Osborne, Marwan N. Sabbagh, Donald J. Connor, Geoffrey L. Ahern, Leslie C. Baxter, Steven Z. Rapcsak, Jiong Shi, Bryan K. Woodruff, Dona E.C. Locke, Charlene Hoffman Snyder, Gene E. Alexander, Rosa Rademakers, Eric M. Reiman
Journal: New England Journal of Medicine (2009)

The APOE ε4 allele is associated with the risk of late-onset Alzheimer's disease. The age at which memory decline diverges among persons who are homozygous for the APOE ε4 allele, those who are heterozygous for the allele, and noncarriers is unknown.
<i>Asp299Gly</i> and <i>Thr399Ile</i> Genotypes of the <i>TLR4</i> Gene Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 2 Diabetes
Authors: Gottfried Rudofsky, Peter Reismann, Steffen Witte, Per M. Humpert, Berend Isermann, Triantafyllos Chavakis, Jörg Tafel, Valery V. Nosikov, Andreas Hamann, Peter Nawroth, Angelika Bierhaus
Journal: Diabetes Care (2004)

OBJECTIVE—To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications. RESEARCH DESIGN AND METHODS—The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases. RESULTS—No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P = 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19–0.61]; P = 0.0002); no association with diabetic nephropathy was found. CONCLUSIONS—Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes.
Abstract 1065: Class-II Histone Deacetylases Regulate Myofilament Calcium Sensitivity in the Mouse Heart
Authors: Stephen H Smith, Mahesh P Gupta, Sadhana Samant, Madhu Gupta, Sanjeev G Shroff
Journal: Circulation (2007)

The role of phosphorylation of myofilaments in regulating cardiac muscle calcium sensitivity and force production is well established. Recently it was shown that trichostatin A (TSA), a class-I and II histone deacetylase (HDAC) inhibitor, improved cardiac contractile function in vivo . Because class-II HDACs are able to translocate to the cytoplasm from the nucleus, it is postulated that some HDACs may interact with contractile proteins and thereby regulate myofilament calcium sensitivity and/or force production. Papillary muscle strips from mouse hearts were skinned for 4 hours and then treated overnight with two structurally dissimilar HDAC inhibitors, TSA and MS275. Both HDAC inhibitors significantly increased myofilament calcium sensitivity as quantified by pCa 50 [Baseline (n=9): 5.75±0.04; TSA (n=6): 5.84±0.02; MS275 (n=7): 5.87±0.03; P &lt;0.05 vs . Baseline], without any significant changes in maximally activated force. Similar increase in calcium sensitivity was also observed when skinned fibers were incubated overnight in a buffer containing acetyl-CoA [acetyl-CoA (n=6): 5.84±0.04; P &lt;0.05 vs . Baseline]. These observations suggest that acetylation of myofilament proteins can regulate myofilament calcium sensitivity. Western blot analyses of skinned fibers revealed that HDAC4 and HDAC5 were specifically associated with myofilament proteins, and acetylation of several myofilament proteins was increased following TSA treatment. One of these acetylated proteins was identified as muscle LIM protein (MLP). Protein-protein interaction analyses and co-localization studies showed that MLP specifically binds to HDAC4. Functional studies with skinned fibers isolated from MLP knock out [MLP −/− ] mice (C57BL6 strain) indicated that TSA-induced increase in calcium sensitivity was completely prevented [MLP −/− -Baseline (n=6): 5.60±0.03; MLP −/− -TSA (n=6): 5.61±0.02; P &lt;NS] compared to wild-type (WT) mice of the same strain [WT-Baseline (n=6): 5.59±0.02; WT-TSA (n=6): 5.70±0.02; P &lt;0.05]. These data demonstrate, for the first time, that class-II HDACs bind to cardiac myofilament proteins, with MLP being one of the binding partners, and play a role in regulating myofilament contractile function.
Irritable bowel syndrome in twins: genes and environment
Authors: M-B Bengtson, T Ronning, M H Vatn, J R Harris
Journal: Gut (2006)

<b>Background and aims:</b> Both environmental and genetic factors may contribute to irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental factor, seems to influence the development of chronic diseases later in life, such as coronary heart disease, hypertension, and non-insulin diabetes. This population based twin study evaluated the association between intrauterine growth, measured by weight and gestational age, and IBS. Structural equation analyses were conducted to analyse genetic and environmental sources of variation in liability to IBS. <b>Methods:</b> A postal questionnaire was sent to 12 700 Norwegian twins born between 1967 and 1979. The questionnaire included a checklist of 31 illnesses and symptoms, including IBS. The influence of birth weight on developing IBS was tested in four weight groups. Disease discordant monozygotic (MZ) pairs were analysed to test the association between intrauterine growth and IBS. <b>Results:</b> Concordance for IBS was significantly greater (p = 0.011) in monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the development of IBS, which appeared 7.7 years earlier than in higher weight groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were significantly lighter than twins without disease (190.6 g; p = 0.02). <b>Conclusion:</b> The present study demonstrates that restricted fetal growth has a significant influence on the development of IBS later in life. Weight below 1500 g influences age at onset. Genetic contribution appears to be important for IBS among females.
From association to causality: the new frontier for complex traits
Authors: Nicholas Katsanis
Journal: Genome Medicine (2009)

Technological and analytical advances have led to an unprecedented catalog of genomic regions associated with a broad range of clinically relevant phenotypes in humans. However, some examples notwithstanding, the causes of the overwhelming majority of genetic diseases remain obscure. More importantly, an emerging lesson from genome-wide association studies is that, in most instances, the resolution necessary for identifying actual genes that underlie the phenotype is limited, as is our ability to develop mechanistic, testable disease models from such studies. These new realities will probably necessitate a paradigm shift in our approach to complex traits, for which the combinatorial application of genomic and functional studies will be necessary to understand the mechanism and pathology of genetic disease. Here I will discuss these issues and highlight how additional sequencing and genotyping of ever-increasing cohort sizes without functional interpretation is unlikely to improve our ability to dissect the genetic basis of complex traits.
David Robert Harvey
Authors: N. Modi
Journal: BMJ (2010)

David Robert Harvey, emeritus professor of paediatrics and neonatal medicine at Imperial College London, has died aged 74, after a long struggle against Parkinson’s disease. David was a leader among the medical lesbian and gay community, paediatrician at the confinements of HRH the Princess Anne in 1977 and 1981, and HRH the Princess of Wales in 1982 and 1984, an educator, researcher, socialist, Buddhist, bon vivant, polymath, and, above all, a champion for the disadvantaged and an advocate for mothers and babies.

Prior to the 1970s very few preterm babies survived. After qualifying in 1960 from Guy’s Hospital Medical School, David trained with Pamela Davies, Peter Tizard, Otto Woolf, John …
Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study
Authors: H Chinoy, S Adimulam, F Marriage, P New, M Vincze, E Zilahi, A Kapitány, A Gyetvai, L Ekholm, P Novota, M Remakova, P Charles, N J McHugh, L Padyukov, L Alfredsson, J Vencovsky, I E Lundberg, K Danko, W E Ollier, R G Cooper
Journal: Annals of the Rheumatic Diseases (2011)

HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM.IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation.557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure.Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.
Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice
Authors: Vishal Singh, Benoit Chassaing, Limin Zhang, Beng San Yeoh, Xia Xiao, Manish Kumar, Mark T. Baker, Jingwei Cai, Rachel Walker, Kamil Borkowski, Kevin J. Harvatine, Nagendra Singh, Gregory C. Shearer, James M. Ntambi, Bina Joe, Andrew D. Patterson, Andrew T. Gewirtz, Matam Vijay-Kumar
Journal: Cell Metabolism (2015)
Morphological Predictors of Restenosis After Coronary Stenting in Humans
Authors: Andrew Farb, Deena K. Weber, Frank D. Kolodgie, Allen P. Burke, Renu Virmani
Journal: Circulation (2002)

Experimental studies suggest that arterial injury and inflammation lead to increased neointimal growth after stenting. Despite the increased use of coronary stents in humans, there are only limited pathological data on the morphological features of in-stent restenosis.Detailed histology was performed on 116 stents, implanted > or =90 days in 87 coronary arteries, from 56 patients (mean age, 59+/-13 years). The mean duration of stent implant was 10 months. In-stent restenosis was defined as a stent area stenosis of >75%. Lumen area increased as stent area increased (r2=0.27, P=0.0001), but there was a much stronger correlation between stent area and neointimal area (r2=0.70, P<0.0001). Arterial medial fracture was associated with a 29% increase (P<0.01) in neointimal thickness compared with arteries with an intact media. Neointimal thickness (P=0.0001), inflammatory cell density (P<0.0001), and neointimal vascular channel density (P<0.0001) were greater when struts were in contact with a ruptured arterial media compared with fibrous plaque or an intact fibrous cap. Stent strut penetration into a lipid core was associated with increased neointimal thickness (P=0.04) and inflammatory cell density (P=0.03). Neointimal inflammatory cell content was 2.4-fold greater in stents with restenosis versus no restenosis, and inflammation was associated with increased neoangiogenesis.Coronary stenting that is accompanied by medial damage or penetration of the stent into a lipid core induces increased arterial inflammation, which is associated with increased neointimal growth. These data suggest the use of stenting strategies that reduce inflammation and neoangiogenesis to reduce the incidence of restenosis.