tbuckley/cabot-search huggingface dataset:
New insights into the experience of fatigue among patients with rheumatoid arthritis: a qualitative study
Authors: S. Nikolaus, C. Bode, E. Taal, M. A. F. J. van de Laar
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives</h3> Patients with rheumatoid arthritis (RA) commonly experience fatigue. The aim of this study was to gain further insight into the experience of fatigue in RA. <h3>Methods</h3> Participants were 31 outpatients with RA of Medical Spectrum Twente, Enschede, The Netherlands, with all levels of fatigue. In-depth structured interviews on the patients9 experience of fatigue were conducted and analysed using a bottom-up coding scheme, meaning that answers of patients were summarised and categorised. <h3>Results</h3> Patients9 mean fatigue severity score was 50 (visual analogue scale (VAS); theoretical range 0–100). Interviews showed interindividual differences in the experience and impact of fatigue. Different patterns in emotions, consequences and management of fatigue were found. Especially younger women with multiple daily roles seemed to be vulnerable to the negative impact of RA fatigue. Patients also reported positive aspects of fatigue. Moreover, varying forms of fatigue were described. <h3>Conclusions</h3> Results point to the existence of differences in fatigue experience according to gender, age and daily roles. This finding indicates a need for targeting advice and interventions to the individual situation of a patient. Furthermore, the positive aspects patients reported about their fatigue could facilitate an approach that is focused on remaining opportunities and not just on restrictions.
Mental Imagery: Functional Mechanisms and Clinical Applications
Authors: Joel Pearson, Thomas Naselaris, Emily A. Holmes, Stephen M. Kosslyn
Journal: Trends in Cognitive Sciences (2015)

Mental imagery research has weathered both disbelief of the phenomenon and inherent methodological limitations. Here we review recent behavioral, brain imaging, and clinical research that has reshaped our understanding of mental imagery. Research supports the claim that visual mental imagery is a depictive internal representation that functions like a weak form of perception. Brain imaging work has demonstrated that neural representations of mental and perceptual images resemble one another as early as the primary visual cortex (V1). Activity patterns in V1 encode mental images and perceptual images via a common set of low-level depictive visual features. Recent translational and clinical research reveals the pivotal role that imagery plays in many mental disorders and suggests how clinicians can utilize imagery in treatment.
Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice
Authors: Anna Dikalova, Roza Clempus, Bernard Lassègue, Guangjie Cheng, James McCoy, Sergey Dikalov, Alejandra San Martin, Alicia Lyle, David S. Weber, Daiana Weiss, W. Robert Taylor, Harald H.H.W. Schmidt, Gary K. Owens, J. David Lambeth, Kathy K. Griendling
Journal: Circulation (2005)

Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources of reactive oxygen species in the vessel wall, but the importance of individual Nox homologues in specific layers of the vascular wall is unclear. Nox1 upregulation has been implicated in cardiovascular pathologies such as hypertension and restenosis.To investigate the pathological role of Nox1 upregulation in vascular smooth muscle, transgenic mice overexpressing Nox1 in smooth muscle cells (TgSMCnox1) were created, and the impact of Nox1 upregulation on the medial hypertrophic response during angiotensin II (Ang II)-induced hypertension was studied. These mice have increased expression of Nox1 protein in the vasculature, which is accompanied by increased superoxide production. Infusion of Ang II (0.7 mg/kg per day) into these mice for 2 weeks led to a potentiation of superoxide production compared with similarly treated negative littermate controls. Systolic blood pressure and aortic hypertrophy were also markedly greater in TgSMCnox1 mice than in their littermate controls. To confirm that this potentiation of vascular hypertrophy and hypertension was due to increased ROS formation, additional groups of mice were coinfused with the antioxidant Tempol. Tempol decreased the level of Ang II-induced aortic superoxide production and partially reversed the hypertrophic and hypertensive responses in these animals.These data indicate that smooth muscle-specific Nox1 overexpression augments the oxidative, pressor, and hypertrophic responses to Ang II, supporting the concept that medial Nox1 participates in the development of cardiovascular pathologies.
Mechanism of action of intradiscal chymopapain in the treatment of sciatica: a clinical, biochemical, and radiological study.
Authors: J R Jenner, D J Buttle, A K Dixon
Journal: Annals of the Rheumatic Diseases (1986)

Seventeen patients with intractable sciatica due to prolapse of a lumbar disc, treated by intradiscal injection of chymopapain (chemonucleolysis) were studied. Analysis of serial 24 hour urine collections showed a significant increase in urinary glycosaminoglycan after chemonucleolysis. This was not detected in four patients undergoing routine discography. Enzymic analysis of urinary glycosaminoglycan after chemonucleolysis suggested that the increase in levels was largely due to an increase in the amounts of chondroitin sulphate present, probably resulting from proteoglycan breakdown in the intervertebral disc. Eight of the patients treated by chemonucleolysis underwent serial computed tomography (CT). One month after the injection the only change seen was a loss of definition of the disc prolapse, which could be interpreted as a loss of turgidity in the disc as a result of proteoglycan breakdown by chymopapain. By six months the CT of those patients whose symptoms had improved showed that the degree of disc prolapse was usually less marked and the disc margin more clearly defined, suggesting that by this stage anatomical remodelling had occurred.
Intraoperative fluid management guided by oesophageal Doppler monitoring
Authors: M. Kuper, S. J. Gold, C. Callow, T. Quraishi, S. King, A. Mulreany, M. Bianchi, D. H. Conway
Journal: BMJ (2011)

Fluid management during major surgery poses a challenge to the surgical team as postoperative complications are often related to giving the wrong amount of intravenous fluid. Postoperative morbidity can be reduced by using the oesophageal Doppler cardiac output monitor to individualise fluid administration, but this technology has not been widely adopted.A campaign for adopting this technology in major surgical specialties explored clinical and managerial barriers throughout the procurement and implementation process. We compared patient outcomes 12 months before implementation and after implementation.Three large hospitals in England with different size, geographical location, and case mix.Project leads at each site included a consultant anaesthetist, a divisional manager, and an audit facilitator. A business case was prepared by each team with support from NHS Technology Adoption Centre, allowing senior management to overcome the unequal spread of costs versus benefits. A survey of anaesthetists revealed concerns about familiarity with the device, which we dealt with by clinicians volunteering to "champion" the technique, supported by standard training provided by the manufacturer. We encouraged appropriate use of the technology by collecting intraoperative patient related data and postoperative patient outcomes and by giving regular, timely feedback.The key outcome measure was length of hospital stay. In-hospital mortality, readmission, and reoperation rates were also recorded. Process measures were use of monitors and change in stroke volume during surgery. EFFECTS OF THE CHANGE: We compared 649 patients after implementation across all sites with 658 matched cases before implementation. Use of Doppler increased from 11% to 65% of eligible operations, with a 3.7 day reduction in total length of stay. Length of stay was reduced at each site, and in most specialties. Concurrent improvements in patient care could have contributed to these findings. The only sign of harm from the intervention was one episode of pulmonary oedema. Mortality, readmission, and reoperation rates all fell non-significantly.Managerial barriers consisted of silo budgeting, difficulties with preparing a business case, and fears about uncontrolled implementation. By collecting outcome data, we convinced senior managers to support and sustain investment. Clinical barriers consisted mainly of scepticism regarding clinical effectiveness and worries about training. Clinicians "championing" the technology took on responsibility for data collection, education, advocacy, and spanning boundaries. When barriers to adoption of oesophageal Doppler monitoring are overcome, outcome improvements suggested by research can be replicated in the real world. The project generated a web based guide (www.howtowhyto.nhs.uk) to provide tools and resources to support implementation.
On Nudging and Informed Consent—Four Key Undefended Premises
Authors: J. S. Swindell Blumenthal-Barby
Journal: The American Journal of Bioethics (2013)

In his article “Nudging and Informed Consent,” Shlomo Cohen (2013) argues, among other things, that 1) “to the extent that the nudge-influenced decision making is rational—in whatever sense,” there...
Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia
Authors: Huimin Geng, Christian Hurtz, Kyle B. Lenz, Zhengshan Chen, Dirk Baumjohann, Sarah Thompson, Natalya A. Goloviznina, Wei-Yi Chen, Jianya Huan, Dorian LaTocha, Erica Ballabio, Gang Xiao, Jae-Woong Lee, Anne Deucher, Zhongxia Qi, Eugene Park, Chuanxin Huang, Rahul Nahar, Soo-Mi Kweon, Seyedmehdi Shojaee, Lai N. Chan, Jingwei Yu, Steven M. Kornblau, Janetta J. Bijl, B. Hilda Ye, K. Mark Ansel, Elisabeth Paietta, Ari Melnick, Stephen P. Hunger, Peter Kurre, Jeffrey W. Tyner, Mignon L. Loh, Robert G. Roeder, Brian J. Druker, Jan. A. Burger, Thomas A. Milne, Bill H. Chang, Markus Müschen
Journal: Cancer Cell (2015)
Western diet impairs metabolic remodelling and contractile efficiency in cardiac hypertrophy
Authors: A. Akki, A.-M. L. Seymour
Journal: Cardiovascular Research (2008)

Metabolic remodelling in cardiac hypertrophy is underscored by a reduction in fatty acid (FA) oxidation. We tested whether this decline in FA oxidation in the presence of enhanced FA supply may predispose the hypertrophied myocardium to lipid accumulation, functional deterioration, and eventually heart failure. and results Left ventricular hypertrophy was induced surgically in Sprague–Dawley rats by inter-renal aortic constriction. Rats were fed a Western diet (WD, 45% kcal from lipids) or standard diet (SD, 12% kcal from fat) for 9 weeks post-surgery. Hearts were perfused in the isovolumic mode with a physiological mixture of substrates including 5 mM 1-13C glucose, 1 mM 3-13C lactate, and 0.3 mM U-13C palmitate, and cardiac function was monitored. Real-time PCR was used to determine transcript levels of peroxisome proliferator-activated receptor-α (PPARα) and PPARα-regulated metabolic enzymes. Palmitate oxidation and PPARα-regulated gene expression were markedly reduced in the hypertrophied myocardium of rats fed SD. However, 9 weeks of WD normalized both palmitate oxidation and PPARα-regulated gene expression but significantly increased glucose and lactate oxidation in the hypertrophied hearts. This was accompanied by cardiac triglyceride accumulation and a decline in ventricular function despite an increase in oxygen consumption. These results highlight that WD-induced dysregulation of FA metabolism has deleterious functional consequences in cardiac hypertrophy.
Increase in the number of fenestrae in mouse endothelial liver cells by altering the cytoskeleton with cytochalasin B
Authors: Anne-Marie Steffan, Jean-Louis Gendrault, André Kirn
Journal: Hepatology (1987)

Endothelial cells of the hepatic sinusoid isolated from mice livers and maintained in culture display typical fenestrae grouped in sieve plates. Treatment with cytochalasin B led to no significant change in the mean diameter of the fenestrae but to an increase in their number and in the porosity of the cells (percentage of the cellular surface opened by the fenestrae) which attained up to 300% of that of the controls. Scanning electron microscopic observations of Triton-extracted cells revealed that these modifications were related to an alteration of the cytoskeleton. The effect of cytochalasin B could be reversed; 3 hr after removal of the drug, the cells recovered their original aspect with sieve plates scattered over their surface. These observations demonstrate that endothelial fenestrae are inducible structures and that the cytoskeleton seems to be involved in their formation.
Longitudinal, Noninvasive Imaging of T-Cell Effector Function and Proliferation in Living Subjects
Authors: Manishkumar R. Patel, Ya-Fang Chang, Ian Y. Chen, Michael H. Bachmann, Xinrui Yan, Christopher H. Contag, Sanjiv S. Gambhir
Journal: Cancer Research (2010)

Abstract Adoptive immunotherapy is evolving to assume an increasing role in treating cancer. Most imaging studies in adoptive immunotherapy to date have focused primarily on locating tumor-specific T cells rather than understanding their effector functions. In this study, we report the development of a noninvasive imaging strategy to monitor T-cell activation in living subjects by linking a reporter gene to the Granzyme B promoter (pGB), whose transcriptional activity is known to increase during T-cell activation. Because pGB is relatively weak and does not lead to sufficient reporter gene expression for noninvasive imaging, we specifically employed 2 signal amplification strategies, namely the Two Step Transcription Amplification (TSTA) strategy and the cytomegalovirus enhancer (CMVe) strategy, to maximize firefly luciferase reporter gene expression. Although both amplification strategies were capable of increasing pGB activity in activated primary murine splenocytes, only the level of bioluminescence activity achieved with the CMVe strategy was adequate for noninvasive imaging in mice. Using T cells transduced with a reporter vector containing the hybrid pGB–CMVe promoter, we were able to optically image T-cell effector function longitudinally in response to tumor antigens in living mice. This methodology has the potential to accelerate the study of adoptive immunotherapy in preclinical cancer models. Cancer Res; 70(24); 10141–9. ©2010 AACR.
Two-dimensional echocardiographic phase analysis. Its potential for noninvasive localization of accessory pathways in patients with Wolff-Parkinson-White syndrome.
Authors: H F Kuecherer, J A Abbott, E H Botvinick, E D Scheinman, J W O'Connell, M M Scheinman, E Foster, N B Schiller
Journal: Circulation (1992)

BACKGROUND In patients with the preexcitation syndrome who are undergoing transcatheter or surgical ablation, accurate localization of accessory pathways is critical. Because preexcitation is known to alter ventricular activation sequence and result in focal areas with presystolic contraction, we investigated whether phase analysis applied to two-dimensional echocardiographic cine loops objectively identifies these focal areas and can be used to localize ventricular insertion sites of accessory pathways. METHODS AND RESULTS We prospectively obtained phase images in 17 patients (11 males; age range, 11-35 years) during minimal preexcitation in normal sinus rhythm and during maximal preexcitation induced by right atrial pacing. A group of 11 normal subjects (six men; age range, 26-37 years) served as controls. Pathway locations predicted from phase imaging were compared with those predicted from routine 12-lead ECGs, from visual inspection of cine loop images, and from catheter-mounted electrode endocardial mapping. Cross-sectional views in a digital cine loop format were mathematically transformed using a first harmonic Fourier algorithm to obtain the corresponding phase images. Phase angle histograms were derived in eight wall segments. Mean and earliest phase angles were derived by computer analysis to quantitate contraction sequence. We found that during right atrial pacing, phase angles in focal areas markedly deviated from normal--mean phase angles from 33 degrees to 164 degrees, and earliest phase angles from 50 degrees to 180 degrees. Accessory pathways could be precisely localized in 53% of the patients by 12-lead ECG, in 59% by visual inspection of cine loop images, in 82% by phase imaging, and in 94% by a combination of the three methods. CONCLUSIONS Our results suggest that phase imaging, especially when used in combination with cine loop and 12-lead ECG, can be used to localize ventricular insertion sites of accessory pathways and may be clinically useful as a noninvasive adjunct to endocardial mapping in patients with Wolff-Parkinson-White syndrome.
High incidence of autoimmune alterations in chronic myeloid leukemia patients treated with interferon‐α
Authors: J.L. Steegmann, M.J. Requena, P. Martín‐Regueira, R. de la Cámara, F. Casado, F. Rodriguez Salvanés, J.M. Fernández Rañada
Journal: American Journal of Hematology (2003)

Interferon-alpha is the frontline therapy of the majority of chronic myeloid leukemia (CML) patients who are not eligible for bone marrow transplantation. Many patients are treated for long periods, and there is concern about the long-term immune effects of its use. Autoimmune disorders in patients treated with IFN-alpha may be related to the direct immunomodulating properties of IFN or may be linked to a possible toxic effect in target organs, triggering autoimmunity. On the other hand, the immune effects of IFN may play a role in its therapeutic actions. The aims of our study were to assess the incidence of autoimmune phenomena in these patients, and to measure the possible association between the generation of autoimmune phenomena and the antileukemic effect of IFN alpha. Therefore, 46 patients with Ph1(+) CML in the first chronic phase were studied for the appearance of immune complications, their connection to IFN dose, time of appearance, and the possible association with the response to treatment. Autoimmune abnormalities have been found in 28% of our patients. Moreover, a significant association was found between autoimmune alterations and female sex (P = 0.02, OR 4.5, 95% CI 1.13-17.9) and a longer treatment time (1.6 vs. 4.1 years) (P = 0.02; OR 1.01, 95% CI 1-1.02). The Kaplan-Meier estimated probability of obtaining a cytogenetic response was significantly higher in patients who developed autoimmune alterations (P = 0.049), and this difference was also evident in Cox's analysis when controlling with other potentially confounding variables (P = 0.078). We conclude that CML patients treated with IFN alpha have a high incidence of autoimmune phenomenon.
Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice
Authors: Minoru Kihara, Satoshi Umemura, Takeshi Sugaya, Yoshiyuki Toya, Machiko Yabana, Shunichi Kobayashi, Kovichi Tamura, Tetsuo Kadota, Reiji Kishida, Kazuo Murakami, Akiyoshi Fukamizu, Masao Ishii
Journal: Kidney International (1998)
Similar Selective Factors Affect Both between-Gene and between-Exon Divergence in Drosophila
Authors: W. Haerty, B. Golding
Journal: Molecular Biology and Evolution (2009)

As a consequence of alternative splicing, a gene's exons will have different frequencies of inclusion into mature mRNA and different patterns of expression. These differences affect their patterns of evolutionary divergence. Using the recently reannotated genome of Drosophila melanogaster and the genome sequences of four closely related species of the melanogaster subgroup, we investigated the effect of alternative splicing, inclusion level (defined as the number of transcripts an exon is found in), and expression pattern on exon evolution across divergence times ranging from 1 to 12.5 Ma. Genes undergoing alternative splicing have a broader pattern of expression associated with a lower divergence rate in comparison with genes with a single annotated protein isoform. Within genes undergoing alternative splicing, we report a significant effect of inclusion level on exon evolution, as alternatively spliced exons are less conserved than constitutively spliced exons. More generally, there are significant negative correlations between inclusion level and exon evolutionary rates that can be associated with relaxation of selection. A significant effect of expression pattern on evolution rates is also observed. Overall, we found that similar selective factors such as the expression level and the pattern of expression are affecting both gene and exon evolution.
Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity
Authors: Bohua Li, Shu Shi, Weizhu Qian, Lei Zhao, Dapeng Zhang, Sheng Hou, Lei Zheng, Jianxin Dai, Jian Zhao, Hao Wang, Yajun Guo
Journal: Cancer Research (2008)

Abstract Despite the effectiveness of the anti-CD20 monoclonal antibody (mAb) Rituximab (C2B8) in the treatment of B-cell lymphoma, its efficacy remains variable and often modest. It seems likely that a combination of multiple mechanisms, such as complement-dependent cytotoxicity (CDC) and apoptotic signaling, underlies the therapeutic success of anti-CD20 mAbs. Unfortunately, all the current anti-CD20 mAbs effective in CDC are relatively inactive in signaling cell death and vice versa. In this study, we developed two genetically engineered tetravalent antibodies (TetraMcAb) respectively derived from the anti-CD20 mAbs C2B8 and 2F2. TetraMcAbs, with a molecular mass only 25 kDa higher than native divalent antibodies (DiMcAb), were shown not only to be as effective in mediating CDC and antibody-dependent cellular cytotoxicity against B-lymphoma cells as DiMcAbs but also to have antiproliferative and apoptosis-inducing activity markedly superior to that of DiMcAbs. Interestingly, whereas 2F2 and C2B8 were equally effective in inducing cell growth arrest and apoptosis, the functions of their tetravalent versions, 2F2(ScFvHL)4-Fc and C2B8(ScFvHL)4-Fc, were significantly different. 2F2(ScFvHL)4-Fc exhibited exceptionally more potent antiproliferative and apoptosis-inducing activity than that of C2B8(ScFvHL)4-Fc. Immunotherapeutic studies further showed that 2F2(ScFvHL)4-Fc was far more effective in prolonging the survival of severe combined immunodeficient mice bearing systemic Daudi or Raji tumors than C2B8, 2F2, and C2B8(ScFvHL)4-Fc, suggesting that it might be a promising therapeutic agent for B-cell lymphoma. [Cancer Res 2008;68(7):2400–8]