tbuckley/cabot-search huggingface dataset:
Mr. P. Power
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1978)

<h3>Introduction</h3> Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death globally. The physical and psychological symptom burden in severe COPD is significant and yet many of these symptoms go untreated (Elkington <i>et al</i>, 2005). Patients with COPD have far less specialist palliative care input than patients with lung cancer despite a symptom burden at the end of life similar, or indeed greater, than patients with lung cancer (Gore <i>et al</i>, 2000). <h3>Methods</h3> An anonymous questionnaire was completed by respiratory healthcare professionals including respiratory doctors of all grades, physiotherapists and nurses of different backgrounds. The questions focused on perceived ease of predicting prognosis in severe COPD, the initiating of end-of-life discussions in this group, and training received in palliative care. <h3>Results</h3> 100 questionnaires were completed. 67 participants were doctors, from house officers to consultants, 5 physiotherapists, 9 respiratory specialist nurses, 8 Macmillan nurses and 12 respiratory ward nurses. The questionnaire found 76% of participants felt it was a very important or important part of their role to initiate end-of-life discussions in severe COPD and 2% felt it was not, or definitely not part of their role. Participants initiated such discussions frequently or very frequently in 20%, and infrequently or very infrequently in 55%. Prognosis in severe COPD was difficult or very difficult in 63% and straightforward or very straightforward in 6%. This is consistent with literature (Gott <i>et al</i>, 2009). Training participants had received in palliating symptoms in this patient group was significant or extensive in 25% and minimal or little in 41%. Training in initiating end-of-life discussions was significant or extensive in 19% and minimal or little in 44%. Training in services available to this group of patients was significant or extensive in 17% and minimal or little in 42%. <h3>Conclusion</h3> The need to initiate end-of-life discussions in severe COPD is felt to be important to the multidisciplinary team9s role in palliating such patients, yet very few regularly have such discussions. A lack of training and self-reported difficulty in predicting prognosis in this group are perceived to be great, and are suggested as possible reasons for this imbalance.
Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression
Authors: Mayumi Nagashimada, Hiroshi Ohta, Chong Li, Kazuki Nakao, Toshihiro Uesaka, Jean-François Brunet, Jeanne Amiel, Delphine Trochet, Teruhiko Wakayama, Hideki Enomoto
Journal: Journal of Clinical Investigation (2012)

The most common forms of neurocristopathy in the autonomic nervous system are Hirschsprung disease (HSCR), resulting in congenital loss of enteric ganglia, and neuroblastoma (NB), childhood tumors originating from the sympathetic ganglia and adrenal medulla. The risk for these diseases dramatically increases in patients with congenital central hypoventilation syndrome (CCHS) harboring a nonpolyalanine repeat expansion mutation of the Paired-like homeobox 2b (PHOX2B) gene, but the molecular mechanism of pathogenesis remains unknown. We found that introducing nonpolyalanine repeat expansion mutation of the PHOX2B into the mouse Phox2b locus recapitulates the clinical features of the CCHS associated with HSCR and NB. In mutant embryos, enteric and sympathetic ganglion progenitors showed sustained sex-determining region Y (SRY) box10 (Sox10) expression, with impaired proliferation and biased differentiation toward the glial lineage. Nonpolyalanine repeat expansion mutation of PHOX2B reduced transactivation of wild-type PHOX2B on its known target, dopamine β-hydroxylase (DBH), in a dominant-negative fashion. Moreover, the introduced mutation converted the transcriptional effect of PHOX2B on a Sox10 enhancer from repression to transactivation. Collectively, these data reveal that nonpolyalanine repeat expansion mutation of PHOX2B is both a dominant-negative and gain-of-function mutation. Our results also demonstrate that Sox10 regulation by PHOX2B is pivotal for the development and pathogenesis of the autonomic ganglia.
Belimumab and the measurement of fatigue
Authors: Davide Mazzoni
Journal: Annals of the Rheumatic Diseases (2015)

I read with great interest the article by Strand et al .1 The aim of the study was to assess the effects of belimumab treatment plus standard systemic lupus erythematosus (SLE) therapy on health-related quality of life in patients with active, autoantibody-positive SLE. Of particular interest are the results about the impact of belimumab on fatigue scores.

Fatigue is a common complaint of patients with SLE and is associated with diminished ability to function.2 ,3 In the majority of cases, the cause of fatigue is still unexplained and it is likely that many factors together lead to lupus fatigue.2 However, until recently, clinical trials have not routinely assessed fatigue.3

The article by …
The Androgen Receptor Induces Integrin α6β1 to Promote Prostate Tumor Cell Survival via NF-κB and Bcl-xL Independently of PI3K Signaling
Authors: Laura E. Lamb, Jelani C. Zarif, Cindy K. Miranti
Journal: Cancer Research (2011)

Abstract Recent studies indicate that androgen receptor (AR) signaling is critical for prostate cancer cell survival, even in castration-resistant disease wherein AR continues to function independently of exogenous androgens. Integrin-mediated adhesion to the extracellular matrix is also important for prostate cell survival. AR-positive prostate cancer cells express primarily integrin α6β1 and adhere to a laminin-rich matrix. In this study, we show that active nuclear-localized AR protects prostate cancer cells from death induced by phosphoinositide 3-kinase (PI3K) inhibition when cells adhere to laminin. Resistance to PI3K inhibition is mediated directly by an AR-dependent increase in integrin α6β1 mRNA transcription and protein expression. Subsequent signaling by integrin α6β1 in AR-expressing cells increased NF-κB activation and Bcl-xL expression. Blocking AR, integrin α6, NF-κB, or Bcl-xL concurrent with inhibition of PI3K was sufficient and necessary to trigger death of laminin-adherent AR-expressing cells. Taken together, these results define a novel integrin-dependent survival pathway in prostate cancer cells that is regulated by AR, independent of and parallel to the PI3K pathway. Our findings suggest that combined targeting of both the AR/α6β1 and PI3K pathways may effectively trigger prostate cancer cell death, enhancing the potential therapeutic value of PI3K inhibitors being evaluated in this setting. Cancer Res; 71(7); 2739–49. ©2011 AACR.
National Profile of Practice Patterns for Hemodialysis Vascular Access in the United States
Authors: Donal Reddan, Preston Klassen, Diane L. Frankenfield, Lynda Szczech, Steve Schwab, Joseph Coladonato, Michael Rocco, Edmund G. Lowrie, William F. Owen
Journal: Journal of the American Society of Nephrology (2002)

The Centers for Medicare & Medicaid Service's (CMS), national End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project is a data collection initiative to identify opportunities for improvement of care to adult, Medicare maintenance dialysis beneficiaries. This analysis of 1999 CPM data characterizes the profile of hemodialysis vascular access in the United States and identifies determinants of vascular access type 2 yr after the translation of vascular access clinical practice guideline statements into national CPMs. CPM data were collected during October to December 1999 and stratified by the 18 regional ESRD networks. Univariate and multivariable analyses were conducted to examine associations of access type with demographic, laboratory, and geographic variables. Multivariable logistic regression analyses were performed to identify independent variables associated with access type. A total of 8154 hemodialysis patients were sampled; 17% (n = 1399) were incident. Twenty-eight percent were dialyzed through an autologous arteriovenous fistula (AVF), 49% through a prosthetic graft (AVG), and 23% through a percutaneous catheter. Independent predictors of having a catheter for hemodialysis were female gender, white race, incident to hemodialysis status, and lower hemoglobin and serum albumin. For patients with a fistula or AVG, female gender (odds ration [OR], 2.46 [2.18 to 2.78]) and black race (OR, 1.70 [1.50 to 1.93]) were the strongest predictors of dialysis through an AVG. Other predictors of dialysis through an AVG were older age, increased body mass index (BMI), diabetes mellitus as the cause of ESRD, and lower serum albumin. Even in adjusted analyses, there was significant geographic variability with respect to hemodialysis access type. Despite translation of practice guidelines for hemodialysis vascular access into national CPMs, there is substantial geographic variability and gender and racial disparity in angioaccess allocation in the United States. Quality improvement strategies to improve the prevalence of fistulae should focus on selected regions and include physician education about their practice patterns and potential biases.
Molecular Mechanisms Mediating Inhibition of Human Large Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channels by High Glucose
Authors: Tong Lu, Tongrong He, Zvonimir S. Katusic, Hon-Chi Lee
Journal: Circulation Research (2006)

Diabetic vascular dysfunction is associated with an increase in reactive oxygen species (ROS). In this study, we hypothesized that hyperglycemia-induced ROS generation would impair the function of large conductance Ca(2+)-activated K(+) (BK) channels, which are major determinants in vasorelaxation. We found that when cultured in high glucose (HG) (22 mmol/L), HEK293 cells showed a reduction in expressed hSlo current densities, as well as slowed activation and deactivation kinetics. When human coronary smooth muscle cells were cultured in HG, similar findings were observed for the BK currents. HG enhanced superoxide dismutase and suppressed catalase (CAT) expression in HEK293 cells, leading to a significant increase in intracellular ROS. The effects of HG were mimicked by hydrogen peroxide (H(2)O(2)), and hSlo functions were restored by CAT gene transfer. Peroxynitrite inhibited hSlo current density but did not change channel kinetics. The hSloC911A mutant was insensitive to the effects of HG and H(2)O(2). Hence, imbalance of antioxidant enzymes plays a critical role in ROS generation in HG, impairing hSlo functions through H(2)O(2)-dependent oxidation at cysteine 911. This may represent an important fundamental mechanism that contributes to the impairment of vasodilation in diabetes.
THE INTERACTION IN VITRO BETWEEN GROUP B MENINGOCOCCI AND RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Richard B. Roberts
Journal: The Journal of Experimental Medicine (1967)

The interaction in vitro between group B meningococci and rabbit polymorphonuclear leukocytes has been described. Phagocytosis did not occur in the presence of normal rabbit serum. Antiserum collected 12-21 days following one subcutaneous inoculation of living log phase meningococci exhibited opsonic activity with type specificity; this opsonic action depended on both heat-labile and heat-stable factors. Following ingestion by granulocytes, meningococci were rapidly killed. These studies suggest that group B meningococcal strains contain specific antiphagocytic surface factors of an as yet unknown chemical nature. Antisera obtained 4 or more wk after immunization showed bactericidal activity with the same type specificity as opsonic activity. This bactericidal activity was also lost after heating and restored by the addition of normal serum. Further studies on opsonins and bactericidins for meningococci may shed light on virulence factors in these microorganisms, and may prove useful for a more precise classification of meningococci according to type rather than group specificity.
Comparison of Human Leukocyte Antigen DR-DQ Disease Associations Found With Cervical Dysplasia and Invasive Cervical Carcinoma
Authors: Raymond J. Apple, Thomas M. Becker, Cosette M. Wheeler, Henry A. Erlich
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Comparison of Human Leukocyte Antigen DR-DQ Disease Associations Found With Cervical Dysplasia and Invasive Cervical Carcinoma Get access Raymond J. Apple, Raymond J. Apple Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas M. Becker, Thomas M. Becker Search for other works by this author on: Oxford Academic PubMed Google Scholar Cosette M. Wheeler, Cosette M. Wheeler Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry A. Erlich Henry A. Erlich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 427–436, https://doi.org/10.1093/jnci/87.6.427 Published: 15 March 1995 Article history Received: 11 July 1994 Revision received: 07 November 1994 Accepted: 06 January 1995 Published: 15 March 1995
Mechanisms of Autoimmune Thyroid Diseases: From Genetics to Epigenetics
Authors: Yaron Tomer
Journal: Annual Review of Pathology Mechanisms of Disease (2014)

Recent advances in our understanding of genetic-epigenetic interactions have unraveled new mechanisms underlying the etiology of complex autoimmune diseases. Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of the population. The major AITDs include Graves disease (GD) and Hashimoto's thyroiditis (HT); although these diseases contrast clinically, their pathogenesis involves shared immunogenetic mechanisms. Genetic data point to the involvement of both shared and unique genes. Among the shared susceptibility genes, HLA-DRβ1-Arg74 (human leukocyte antigen DR containing an arginine at position β74) confers the strongest risk. Recent genome-wide analyses have revealed new putative candidate genes. Epigenetic modulation is emerging as a major mechanism by which environmental factors interact with AITD susceptibility genes. Dissecting the genetic-epigenetic interactions underlying the pathogenesis of AITD is essential to uncover new therapeutic targets.
Will steroidal aromatase inhibitors induce rheumatoid arthritis?
Authors: B. Morel, H. Marotte, P. Miossec
Journal: Annals of the Rheumatic Diseases (2006)

Aromatase inhibitors are used in advanced breast cancer treatment to cause an oestrogen deprivation. Such treatment can induce benign arthralgias.1,2 We describe a case of rheumatoid arthritis after treatment with aromatase inhibitors. A 64-year-old Caucasian woman, with a 3-year history of advanced right breast cancer (infiltrative ductal carcinoma classified as oestrogen-receptor positive; progesterone-receptor negative with positive lymph nodes; pT2pN1bM0) received treatment with tamoxifen (20 mg/day) for about 3 years. Cancer follow-up was normal and no side effects were reported. In November 2004, tamoxifen was switched to exemestane (25 mg/day) in accordance with studies showing better efficacy and good safety. A few days later, she developed arthralgias affecting the hips, shoulders, knees, wrists and hands associated with morning joint stiffness for 2 h. …
Social cost of land mines in four countries: Afghanistan, Bosnia, Cambodia, and Mozambique
Authors: N. Andersson, C. P. da Sousa, S. Paredes
Journal: BMJ (1995)

<h3>abstract</h3> <b>Objectives</b>:To document the effects of land mines on the health and social conditions of communities in four affected countries. <b>Design</b>:A cross design of cluster survey and rapid appraisal methods including a household questionnaire and qualitative data from key informants, institutional reviews, and focus groups of survivors of landmines from the same communities. <b>Setting</b>:206 communities, 37 in Afghanistan, 66 in Bosnia, 38 in Cambodia, and 65 in Mozambique <b>Subjects</b>:174489 people living in 32904 households in the selected communities. <b>Main outcome measures</b>:Effects of land mines on food security, residence, livestock, and land use; risk factors: extent of individual land mine injuries; physical, psychological, social, and economic costs of injuries during medical care and rehabilitation. <b>Results</b>:Between 25% and 87% of households had daily activities affected by land mines. Based on expected production without the mines, agricultural production could increase by 88-200% in different regions of Afghanistan, 11% in Bosnia, 135% in Cambodia, and 3.6% in Mozambique. A total of 54554 animals was lost because of land mines, with a minimum cash value of $6.5m, or nearly $200 per household. Overall, 6% of households (1964) reported a land mine victim; a third of victims died in the blast. One in 10 of the victims was a child. The most frequent activities associated with land mine incidents were agricultural or pastoral, except in Bosnia where more than half resulted from military activities, usually during patrols. Incidences have more than doubled between 1980-3 and 1990-3, excluding the incidents in Bosnia. Some 22% of victims (455/2100) were from households reporting attempts to remove land mines; in these households there was a greatly increased risk of injury (odds ratio 4.2 and risk difference 19% across the four countries). Lethality of the mines varied; in Bosnia each blast killed an average of 0.54 people and injured 1.4, whereas in Mozambique each blast killed 1.45 people and wounded 1.27. Households with a land mine victim were 40% more likely to experience difficulty in providing food for the family. Family relationships were affected for around one in every four victims and relationships with colleagues in 40%. <b>Conclusions</b>:Land mines seriously undermine the economy and food security in affected countries; they kill and maim civilians at an increasing rate. The expense of medical care and rehabilitation add economic disability to the physical burden. Awareness of land mines can be targeted at high risk attitudes, such as those associated with tampering with mines.
About the Benefits of Immunotherapy for High-Risk Neuroblastoma
Authors: Lucas Moreno, Giuseppe Barone, Julie R. Park, Andrew D.J. Pearson
Journal: Journal of Clinical Oncology (2013)

porting the Memorial Sloan-Kettering Cancer Center's institutional experience using immunotherapy for the treatment of high-risk neuroblastoma. There is an unmet need to develop novel ther- apies for children with neuroblastoma, and the longstanding efforts of the Memorial Sloan-Kettering Cancer Center team in developing immunotherapy approaches over the last three de- cades should be commended. The article 1 presents interesting data about the changing pattern of relapse after immunotherapy as well as about novel biomarkers, such as the clearance of minimal residual disease before and after immunotherapy using an mRNA marker panel andtheuseof FCGR2Apolymorphisms,humanleukocyteantigen, and killer immunoglobulin-like receptor genotyping. FivelevelsofevidencehavebeendescribedbytheOxfordCentre
Evaluation of Colon Cancer–Specific Antigen 2 as a Potential Serum Marker for Colorectal Cancer
Authors: Eddy S. Leman, Robert E. Schoen, Ahmed Magheli, Lori J. Sokoll, Daniel W. Chan, Robert H. Getzenberg
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A blood test to detect colon cancer at a preventable stage would represent a major advancement. We have previously identified colon cancer–specific markers using focused proteomics analysis of nuclear structural proteins. Two of these markers, colon cancer–specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is a distinct novel colon cancer marker identified using focused proteomics. Experimental Design: Using an indirect ELISA on serum samples obtained from two institutions, we evaluated CCSA-2 as a serum-based colon cancer marker. A total of 111 serum samples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study. Results: Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 μg/mL has overall specificity of 78.4% [95% confidence interval (95% CI), 67.3-87.1%] and sensitivity of 97.3% (95% CI, 85.8-99.5%) in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90 (95% CI, 0.83-0.95). Conclusion: Our initial study shows that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity.
Prevalence of copy-number neutral LOH in glioblastomas revealed by genomewide analysis of laser-microdissected tissues
Authors: Daisuke Kuga, Masahiro Mizoguchi, Yanlei Guan, Nobuhiro Hata, Koji Yoshimoto, Tadahisa Shono, Satoshi O. Suzuki, Yoji Kukita, Tomoko Tahira, Shinji Nagata, Tomio Sasaki, Kenshi Hayashi
Journal: Neuro-Oncology (2008)

We have employed a laser-capture microdissection technique and single-nucleotide polymorphism arrays to characterize genomic alterations associated with the development of glioblastoma multiforme (GBM). Combined analysis of loss of heterozygosity (LOH) and copy number revealed that more than half (56.3%) of the 254 identified LOH loci showed no copy-number alteration, indicating the presence of copy-number neutral LOH (cnLOH). Furthermore, we found a GBM case that showed cnLOH in 18 of the 22 autosomes. These results were confirmed by quantitative real-time PCR, microsatellite analysis, and fluorescence in situ hybridization. The high rate of cnLOH suggests that epigenetic abnormalities of many genes are involved in the development and progression of GBMs.
Evidence on community based care for people with long term conditions is lacking, say experts
Authors: A. O'Dowd
Journal: BMJ (2013)

No good evidence exists that shifting the focus of NHS care away from hospitals to the community for people with long term conditions makes clinical or economic sense, MPs have been told.

Serious questions should be asked about winding down or merging hospitals while investing more in primary and community care, experts in economics and research told MPs on the parliamentary health select committee.

The committee held the first evidence session of its inquiry into the management of long term conditions on 18 June.

MPs asked witnesses their opinion on the view that better quality and more economic care for people with long term conditions would be achieved only by greater integration of …
Gene expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neo-chemoradiotherapy
Authors: J. Wen, H. Yang, M.Z. Liu, K.J. Luo, H. Liu, Y. Hu, X. Zhang, R.C. Lai, T. Lin, H.Y. Wang, J.H. Fu
Journal: Annals of Oncology (2014)