tbuckley/cabot-search huggingface dataset:
Cross-sectional and longitudinal associations between systemic, subchondral bone mineral density and knee cartilage thickness in older adults with or without radiographic osteoarthritis
Authors: Yuelong Cao, Oliver P Stannus, Dawn Aitken, Flavia Cicuttini, Benny Antony, Graeme Jones, Changhai Ding
Journal: Annals of the Rheumatic Diseases (2013)

To investigate cross-sectional and longitudinal associations between systemic bone mineral density (BMD), subchondral BMD (sBMD) and knee cartilage thickness in older adults with or without radiographic osteoarthritis (ROA).A prospective cohort of 158 randomly selected subjects (mean 63 years, 48% women) including 69 non-ROA and 89 ROA subjects were studied at baseline and 2.7 years later. Knee cartilage thickness was semi-automatically determined from T1-weighted fat-suppressed MRI. Knee cartilage volume was measured from MRI. Systemic BMD and sBMD were measured by dual-energy X-ray absorptiometry (DXA).Cross-sectionally, total body, total hip, spine BMD and/or lateral tibial sBMD were significantly and positively associated with femoral, lateral tibial and/or patellar cartilage thickness in subjects with ROA after adjustment for potential confounders. Longitudinally, a high total body BMD was associated with an increase in femoral cartilage thickness (β: 0.33 mm/g/cm(2), 95% CI 0.13 to 0.53); a high spine BMD was associated with increases in femoral and lateral tibial cartilage thickness (β: 0.25 mm/g/cm(2), 95% CI 0.10 to 0.41; and β: 0.18 mm/g/cm(2), 95% CI: 0.01 to 0.34, respectively) and a high medial tibial sBMD was associated with an increase in medial tibial cartilage thickness (β: 0.45 mm/g/cm(2), 95% CI 0.02 to 0.89) in subjects with ROA. In contrast, there were no significant associations between baseline systemic BMD, sBMD and cartilage volume loss, nor were there associations between BMD and cartilage thickness in subjects without ROA.Both systemic and subchondral BMD are positively associated with increased cartilage thickness in subjects with ROA, suggesting BMD may play a protective role against cartilage loss in knee OA.
ADAM33 Expression in Asthmatic Airways and Human Embryonic Lungs
Authors: Hans Michael Haitchi, Robert M. Powell, Timothy J. Shaw, Peter H. Howarth, Susan J. Wilson, David I. Wilson, Stephen T. Holgate, Donna E. Davies
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations.To study the role of ADAM33 in asthma, we investigated its expression in normal, asthmatic, and embryonic airways using reverse transcriptase-quantitative polymerase chain reaction and immunochemistry.Several ADAM33 mRNA splice variants were detected in bronchial biopsies and embryonic lung; however, the beta-isoform and variants encoding the metalloprotease domain were rare transcripts. Western blotting of bronchial biopsies confirmed the presence of multiple isoforms of ADAM33, which had molecular weights of 22, 37, 55, and 65 kD. Immunohistochemistry and laser confocal microscopy of adult bronchial biopsies showed that alpha-smooth muscle actin and ADAM33 immunoreactivity were mostly colocalized to smooth muscle and isolated cells in the submucosa. There was no significant difference in ADAM33 mRNA amplicons or protein in subjects with asthma compared with control subjects. In developing lung, ADAM33 was found around bronchial tubes; however, immunoreactivity was more widely distributed than alpha-smooth muscle actin within undifferentiated mesenchyme; on Western blots, an additional 25-kD ADAM33 variant was detected.Several ADAM33 protein isoforms occur in adult bronchial smooth muscle and in human embryonic bronchi and surrounding mesenchyme, strongly suggesting its importance in smooth muscle development and/or function, which could explain its genetic association with bronchial hyperresponsiveness. The occurrence of ADAM33 in embryonic mesenchymal cells suggests that it may be involved in airway wall "modeling" that contributes to the early life origins of asthma.
Can peak expiratory flow be measured accuratelyduring a forced vital capacity manoeuvre?
Authors: D. Wensley, D. Pickering, M Silverman
Journal: European Respiratory Journal (2000)

Spirometry and peak flow measurements traditionally depend on different forced expiratory manoeuvres and have usually been performed on separate, dedicated equipment. As spirometry becomes more widely used in primary care settings, the authors wished to determine whether there was a systematic difference between peak expiratory flow (PEF) derived from a short sharp exhalation (PEF manoeuvre) and from a full forced vital capacity (FVC) manoeuvre, using the same turbine spirometer (Microloop, Micro Medical, Kent, UK). Eighty children (38 with current asthma) aged 7-16 yrs were asked to perform 2 blocks of PEF and FVC manoeuvres, the order being randomly assigned. PEF obtained from a peak flow manoeuvre (PEFPF) was significantly greater than that from a forced vital capacity manoeuvre (PEFVC) in both healthy (group mean difference 20 L x min(-1); p&lt;0.001) and asthmatic children (group mean difference 9 L.min(-1); p&lt;0.004). For clinical purposes, a mean difference of about 3% for children with asthma is of no practical significance, and peak expiratory flow data can usefully be obtained during spirometric recordings.
Graphene‐Based Materials in Regenerative Medicine
Authors: Xili Ding, Haifeng Liu, Yubo Fan
Journal: Advanced Healthcare Materials (2015)

Graphene possesses many unique properties such as two-dimensional planar structure, super conductivity, chemical and mechanical stability, large surface area, and good biocompatibility. In the past few years, graphene-based materials have risen as a shining star on the path of researchers seeking new materials for future regenerative medicine. Herein, the recent research advances made in graphene-based materials mostly utilizing the mechanical and electrical properties of graphene are described. The most exciting findings addressing the impact of graphene-based materials on regenerative medicine are highlighted, with particular emphasis on their applications including nerve, bone, cartilage, skeletal muscle, cardiac, skin, adipose tissue regeneration, and their effects on the induced pluripotent stem cells. Future perspectives and emerging challenges are also addressed in this Review article.
Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.
Authors: E Fikrig, S R Telford, R Wallich, M Chen, Y Lobet, F R Matuschka, R B Kimsey, F S Kantor, S W Barthold, A Spielman, R A Flavell
Journal: The Journal of Experimental Medicine (1995)

Diversity and mutations in the genes for outer surface proteins (Osps) A and B of Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme disease, suggests that a monovalent OspA or OspB vaccine may not provide protection against antigenically variable naturally occurring B. burgdorferi. We now show that OspA or OspB immunizations protect mice from tick-borne infection with heterogeneous B. burgdorferi from different geographic regions. This result is in distinct contrast to in vitro killing analyses and in vivo protection studies using syringe injections of B. burgdorferi as the challenge inoculum. Evaluations of vaccine efficacy against Lyme disease and other vector-borne infections should use the natural mode of transmission and not be predicated on classification systems or assays that do not rely upon the vector to transmit infection.
Adjuvant chemotherapy in the treatment of colon cancer: randomized multicenter trial of the Italian National Intergroup of Adjuvant Chemotherapy in Colon Cancer (INTACC)
Authors: F. Di Costanzo, A. Sobrero, S. Gasperoni, L. Dogliotti, L. Frassineti, A. Falcone, R. Lionetto, P. Bruzzi, G. Luppi, L. Gallo, P. Conte, A. Comandone, D. Turci, M. Marzola, U. Folco, E. Pfanner, M. Mestriner, C. Boni, C. Galli, M. Tonato, R. Rosso
Journal: Annals of Oncology (2003)
Do multiple cortical–subcortical interactions support different aspects of consciousness?
Authors: Daniel Collerton, Elaine Perry
Journal: Behavioral and Brain Sciences (2007)

Merker's core idea, that the experience of being conscious reflects the interactions of actions, targets, and motivations in the upper brainstem, with cortex providing the content of the conscious experience, merits serious consideration. However, we have two areas of concern: first, that his definition of consciousness is so broad that it is difficult to find any organisms with a brain that could be non-conscious; second, that the focus on one cortical–subcortical system neglects other systems (e.g., basal forebrain and brainstem cholinergic systems and their cortical and thalamic target areas) which may be of at least equal significance.
Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE
Authors: Vilma Urbonaviciute, Barbara G. Fürnrohr, Silke Meister, Luis Munoz, Petra Heyder, Francesco De Marchis, Marco E. Bianchi, Carsten Kirschning, Hermann Wagner, Angelo A. Manfredi, Joachim R. Kalden, Georg Schett, Patrizia Rovere-Querini, Martin Herrmann, Reinhard E. Voll
Journal: The Journal of Experimental Medicine (2008)

Autoantibodies against double-stranded DNA (dsDNA) and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE). However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Impaired phagocytosis of apoptotic cells with consecutive release of nuclear antigens may contribute to the immune pathogenesis. The architectural chromosomal protein and proinflammatory mediator high mobility group box protein 1 (HMGB1) is tightly attached to the chromatin of apoptotic cells. We demonstrate that HMGB1 remains bound to nucleosomes released from late apoptotic cells in vitro. HMGB1-nucleosome complexes were also detected in plasma from SLE patients. HMGB1-containing nucleosomes from apoptotic cells induced secretion of interleukin (IL) 1beta, IL-6, IL-10, and tumor necrosis factor (TNF) alpha and expression of costimulatory molecules in macrophages and dendritic cells (DC), respectively. Neither HMGB1-free nucleosomes from viable cells nor nucleosomes from apoptotic cells lacking HMGB1 induced cytokine production or DC activation. HMGB1-containing nucleosomes from apoptotic cells induced anti-dsDNA and antihistone IgG responses in a Toll-like receptor (TLR) 2-dependent manner, whereas nucleosomes from living cells did not. In conclusion, HMGB1-nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA.
Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma <i>In Situ</i> to Invasive Breast Cancer
Authors: Sangjun Lee, Sheila Stewart, Iris Nagtegaal, Jingqin Luo, Yun Wu, Graham Colditz, Dan Medina, D. Craig Allred
Journal: Cancer Research (2012)

Molecular mechanisms mediating the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer remain largely unknown. We used gene expression profiling of human DCIS (n = 53) and invasive breast cancer (n = 51) to discover uniquely expressed genes that may also regulate progression. There were 470 total differentially expressed genes (≥2-fold; P < 0.05). Elevated expression of genes involved in synthesis and organization of extracellular matrix was particularly prominent in the epithelium of invasive breast cancer. The degree of overlap of the genes with nine similar studies in the literature was determined to help prioritize their potential importance, resulting in 74 showing overlap in ≥2 studies (average 3.6 studies/gene; range 2-8 studies). Using hierarchical clustering, the 74-gene profile correctly categorized 96% of samples in this study and 94% of samples from 3 similar independent studies. To study the progression of DCIS to invasive breast cancer in vivo, we introduced human DCIS cell lines engineered to express specific genes into a "mammary intraductal DCIS" xenograft model. Progression of xenografts to invasive breast cancer was dramatically increased by suppressing four genes that were usually elevated in clinical samples of DCIS, including a protease inhibitor (CSTA) and genes involved in cell adhesion and signaling (FAT1, DST, and TMEM45A), strongly suggesting that they normally function to suppress progression. In summary, we have identified unique gene expression profiles of human DCIS and invasive breast cancer, which include novel genes regulating tumor progression. Targeting some of these genes may improve the detection, diagnosis, and therapy of DCIS.
Comparison of Systemic and Coronary Hemodynamics in the Normal Human Male and Female
Authors: G. G. ROWE, C. A. CASTILLO, G. M. MAXWELL, C. W. CRUMPTON, D.H. WHITE,, D.J. FREEMAN, L.A. LUCAS
Journal: Circulation Research (1959)

Coronary and systemic hemodynamics were compared in 15 normal men and 15 normal women. Systemic hemodynamics were very similar. The women had 26.5 per cent greater coronary flow and 19.6 per cent more oxygen consumption/100 Gm. of left ventricular myocardium. Their calculated coronary vascular resistance was 35 per cent less. Significant negative correlations between coronary flow and calculated heart weight, and between cardiac oxygen consumption and calculated heart weight, as well as between coronary flow and hematocrit probably explain the differences in part. Whether hormonal or anatomic differences are also significant is not known.
Sox2 Transduction Enhances Cardiovascular Repair Capacity of Blood-Derived Mesoangioblasts
Authors: Masamichi Koyanagi, Masayoshi Iwasaki, Stefan Rupp, Francesco Saverio Tedesco, Chang-Hwan Yoon, Jes-Niels Boeckel, Janina Trauth, Corina Schütz, Kisho Ohtani, Rebekka Goetz, Kazuma Iekushi, Philipp Bushoven, Stefan Momma, Christine Mummery, Robert Passier, Reinhard Henschler, Hakan Akintuerk, Dietmar Schranz, Carmen Urbich, Beatriz G. Galvez, Giulio Cossu, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2010)

Complementation of pluripotency genes may improve adult stem cell functions.Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or mesenchymal stromal cells, and resembles that of embryonic multipotent mesoangioblasts. Cell numbers and proliferative capacity correlated with donor age. Isolated circulating mesoangioblasts (cMABs) express the pluripotency markers Klf4, c-Myc, as well as low levels of Oct3/4, but lack Sox2. Therefore, we tested whether overexpression of Sox2 enhances pluripotency and facilitates differentiation of cMABs in cardiovascular lineages.Lentiviral transduction of Sox2 (Sox-MABs) enhanced the capacity of cMABs to differentiate into endothelial cells and cardiomyocytes in vitro. Furthermore, the number of smooth muscle actin positive cells was higher in Sox-MABs. In addition, pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies. To test whether Sox-MABs may exhibit improved therapeutic potential, we injected Sox-MABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-MABs, cardiac function was significantly improved compared to mice treated with control cMABs. Furthermore, cell therapy with Sox-MABs resulted in increased number of differentiated cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.The complementation of Sox2 in Oct3/4-, Klf4-, and c-Myc-expressing cMABs enhanced the differentiation into all 3 cardiovascular lineages and improved the functional recovery after acute myocardial infarction.
Conical Cornea. Part II
Authors: W. W. Cooper
Journal: BMJ (1850)

Purudnt Eye' (p. 26)where he speaks of ' those rare cases, in which the cornea undergoes a change from its round figure, and assumes a conical or sugar-loaf shape'.For the cure of this, he say's ' he had tried a variety of remedies-evacuation of the aqueous humour, followed by application of compreses ;' but adds, that ' the cornea always resumed its projecting figure.
Association of Comorbid Posttraumatic Stress Disorder and Major Depression With Greater Risk for Suicidal Behavior
Authors: Maria A Oquendo, Jeff M Friend, Batsheva Halberstam, Beth S Brodsky, Ainsley K Burke, Michael F Grunebaum, Kevin M Malone, J John Mann
Journal: American Journal of Psychiatry (2003)

Posttraumatic stress disorder (PTSD) increases the risk of suicidal behavior; a major depressive episode also increases the risk for suicidal behavior. The authors' goal was to examine the effect of comorbid PTSD and major depressive episode on suicidal behavior.Inpatients with a diagnosis of major depressive episode (N=156) were assessed for PTSD, suicidal behavior, and clinical risk factors for suicidal acts.Patients with comorbid major depressive episode and PTSD were more likely to have attempted suicide, and women with both disorders were more likely to have attempted suicide than men with both disorders. Cluster B personality disorder and PTSD were independently related to history of suicide attempts.The greater rate of suicide attempts among patients with comorbid PTSD and major depressive episode was not due to differences in substance use, childhood abuse, or cluster B personality disorders.
Functional Assessment of Chronic Illness Therapy-Fatigue Scale is valid in patients with psoriatic arthritis
Authors: V. Chandran, S. Bhella, C. Schentag, D. D Gladman
Journal: Annals of the Rheumatic Diseases (2007)

Fatigue is an important symptom in psoriatic arthritis (PsA).To determine the reliability and validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT fatigue) Scale in PsA.Consecutive patients attending the PsA clinic were assessed with the FACIT fatigue Scale twice, 1 week apart. Patients were assessed clinically according to a standardised PsA clinic protocol. Internal consistency of the 13 items on the FACIT fatigue questionnaire was measured using Cronbach's alpha; test-retest reliability by the intraclass correlation coefficient (ICC), and validity by the correlation of the FACIT fatigue results with other fatigue measures and disease characteristics.135 patients (80 men and 55 women, mean (SD) age 52 (13) years, mean (SD) disease duration 17 (10) years) participated. The mean FACIT fatigue score was 35.8 (12.4). Cronbach's alpha was 0.96. Repeat questionnaires were returned by 54% of patients. No difference in disease characteristics was observed between those who did and did not return the questionnaires. The ICC for first and repeat FACIT fatigue scores was 0.95. The correlation between the FACIT fatigue and modified Fatigue Severity Score was -0.79 (95% CI -0.85 to -0.72). FACIT fatigue scores were lower in patients with overwhelming fatigue and fibromyalgia than in those without (p<0.001). The FACIT fatigue was correlated with the actively inflamed joint count (-0.43, 95% CI -0.56 to -0.28, p<0.001), but not with the clinically damaged joint count (-0.06, 95% CI -0.23 to 0.11, p = 0.51).The FACIT fatigue results were reproducible, and correlated with other fatigue measures as well as with disease activity in patients with PsA. Therefore, the FACIT fatigue is a reliable and valid instrument to measure fatigue in PsA.
PWE-061 Homozyogosity in the ApoE4 polymorphism is associated with dysphagic symptoms in an otherwise healthy elderly population: Abstract PWE-061 Figure 1
Authors: H Mentz, N Pendleton, S Hamdy
Journal: Gut (2012)

<h3>Introduction</h3> Apolipoprotein E (ApoE) is thought to be the most common genetic risk factor for Alzheimer9s disease and has a number of polymorphisms. While the E2 allele is proposed to play a protective role, it E4 allele is said to increase the risk of cognitive decline. We therefore hypothesised that the presence of ApoE4 would be predictive of dysphagia symptoms. <h3>Methods</h3> 800 members of a genetically well characterised community dwelling elderly cohort received the Sydney oropharyngeal dysphagia questionnaire via mail.<sup>1</sup> Cognitive function was also measured using the Telephone Interview of Cognitive Status and mood with the Geriatric Depression Score (GDS). ApoE4/2 allele status was then correlated with dysphagia symptoms. <h3>Results</h3> Completed questionnaire response rate was 79% (23.5% men, 76.5% women; mean age 81±5 years; range 69–98 years). Possession of one or more of the ApoE4 and 2 alleles was found in 23.5% and 16% respectively. Swallowing score was significantly related to GDS (CC 0.133, p&lt;0.001**) and Age (CC 0.107, p&lt;0.007**). While dysphagia was not significantly associated with possession of single E4 or E2 alleles, ApoE4 homozygosity was associated with significantly higher swallowing scores compared to all other allele combinations (p=0.033). <h3>Conclusion</h3> We have shown a novel relationship between self reported dysphagic symptoms and ApoE genotype in community dwelling older adults. The presence of ApoE4 homozygostiy appears to associate with dysphagia symptoms but requires replication in independent larger cohorts. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Wallace KL</b>, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. <i>Gastroenterology</i> 2000;<b>118</b>:678–87.
Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage
Authors: Arne Lauer, Flor A. Cianchetti, Elizabeth M. Van Cott, Frieder Schlunk, Elena Schulz, Waltraud Pfeilschifter, Helmuth Steinmetz, Chris B. Schaffer, Eng H. Lo, Christian Foerch
Journal: Circulation (2011)

Background— The direct thrombin inhibitor dabigatran etexilate (DE) may constitute a future replacement of vitamin K antagonists for long-term anticoagulation. Whereas warfarin pretreatment is associated with greater hematoma expansion after intracerebral hemorrhage (ICH), it remains unclear what effect direct thrombin inhibitors would have. Using different experimental models of ICH, this study compared hematoma volume among DE-treated mice, warfarin-treated mice, and controls. Methods and Results— CD-1 mice were fed with DE or warfarin. Sham-treated mice served as controls. At the time point of ICH induction, DE mice revealed an increased activated partial thromboplastin time compared with controls (mean±SD 46.1±5.0 versus 18.0±1.5 seconds; P =0.022), whereas warfarin pretreatment resulted in a prothrombin time prolongation (51.4±17.9 versus 10.4±0.3 seconds; P &lt;0.001). Twenty-four hours after collagenase-induced ICH formation, hematoma volume was 3.8±2.9 μL in controls, 4.8±2.7 μL in DE mice, and 14.5±11.8 μL in warfarin mice (n=16; Welch ANOVA between-group differences P =0.007; posthoc analysis with the Dunnett method: DE versus controls, P =0.899; warfarin versus controls, P &lt;0.001; DE versus warfarin, P =0.001). In addition, a model of laser-induced cerebral microhemorrhage was applied, and the distances that red blood cells and blood plasma were pushed into the brain were quantified. Warfarin mice showed enlarged red blood cell and blood plasma diameters compared to controls, but no difference was found between DE mice and controls. Conclusions— In contrast with warfarin, pretreatment with DE did not increase hematoma volume in 2 different experimental models of ICH. In terms of safety, this observation may represent a potential advantage of anticoagulation with DE over warfarin.