tbuckley/cabot-search huggingface dataset:
Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy
Authors: B. Schuhknecht, M. Marziniak, A. Wissel, N.Q. Phan, D. Pappai, J. Dangelmaier, D. Metze, S. Ständer
Journal: British Journal of Dermatology (2011)

Journal Article Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy Get access B. Schuhknecht, B. Schuhknecht Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar M. Marziniak, M. Marziniak Neurology, Competence Center Chronic Pruritus, University Hospital Münster, Von‐Esmarch‐Str. 58, D‐48149 Münster, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Wissel, A. Wissel Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar N.Q. Phan, N.Q. Phan Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar D. Pappai, D. Pappai Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar J. Dangelmaier, J. Dangelmaier Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar D. Metze, D. Metze Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S. Ständer S. Ständer Departments of Dermatology Sonja Ständer. E‐mail: sonja.staender@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 85–91, https://doi.org/10.1111/j.1365-2133.2011.10306.x Published: 01 July 2011
Reflecting on the global burden of musculoskeletal conditions: lessons learnt from the Global Burden of Disease 2010 Study and the next steps forward
Authors: Damian G Hoy, Emma Smith, Marita Cross, Lidia Sanchez-Riera, Fiona M Blyth, Rachelle Buchbinder, Anthony D Woolf, Tim Driscoll, Peter Brooks, Lyn M March
Journal: Annals of the Rheumatic Diseases (2014)

The objective of this paper is to provide an overview of the strengths, limitations and lessons learned from estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It should be read in conjunction with the other GBD 2010 Study papers published in this journal. The strengths of the GBD 2010 Study include: the involvement of a MSK expert group; development of new and more valid case definitions, functional health states, and disability weights to better reflect the MSK conditions; the extensive series of systematic reviews undertaken to obtain data to derive the burden estimates; and the use of a new, more advanced version of the disease-modelling software (DisMod-MR). Limitations include: many regions of the world did not have data; the extent of heterogeneity between included studies; and burden does not include broader aspects of life, such as participation and well-being. A number of lessons were learned. Ongoing involvement of experts is critical to ensure the success of future efforts to quantify and monitor this burden. A paradigm shift is urgently needed among global agencies in order to alleviate the rapidly increasing global burden from MSK conditions. Prevention and control of MSK disability are required, along with health system changes. Further research is needed to improve understanding of the predictors and clinical course across different settings, and the ways in which MSK conditions can be better managed and prevented.
Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations
Authors: D. Figarella-Branger, K. Mokhtari, C. Dehais, A. Jouvet, E. Uro-Coste, C. Colin, C. Carpentier, F. Forest, C.-A. Maurage, J.-M. Vignaud, M. Polivka, E. Lechapt-Zalcman, S. Eimer, G. Viennet, I. Quintin-Roue, M.-H. Aubriot-Lorton, M.-D. Diebold, D. Loussouarn, C. Lacroix, V. Rigau, A. Laquerriere, F. Vandenbos, S. Michalak, H. Sevestre, M. Peoch, F. Labrousse, C. Christov, J.-L. Kemeny, M.-P. Chenard, D. Chiforeanu, F. Ducray, A. Idbaih, C. Desenclos, P. Menei, E. Al Nader, J. Godard, S. Servagi-Vernat, A. Carpentier, H. Loiseau, P. Dam-Hieu, J. S. Guillamo, E. Emery, P. Verelle, X. Durando, T. Faillot, C. Le Guerinel, F. Ghiringhelli, F. Parker, C. Adam, F. Dubois, C. Ramirez, E. M. Gueye, J. Honnorat, O. Chinot, L. Bauchet, P. Beauchesne, M. Campone, J. S. Frenel, D. Fontaine, C. Campello, P. Roger, A. Heitzmann, M. Fesneau, J. Y. Delattre, S. Elouadhani-Hamdi, D. Ricard, P. Colin, E. Vauleon, O. Langlois, M. J. M. Fotso, M. Andraud, S. Mouton, G. Noel, N. Desse, R. Soulard, E. Cohen-Moyal, V. Lubrano, F. Dhermain
Journal: Neuro-Oncology (2014)

The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10−4), IDH1/2 mutation (P < 10−4), chromosome 4 loss (P < 10−3), and better overall survival (P < 10−4). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.
Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine
Authors: Thomas Pabst, Edo Vellenga, Wim van Putten, Harry C. Schouten, Carlos Graux, Marie-Christiane Vekemans, Bart Biemond, Peter Sonneveld, Jakob Passweg, Leo Verdonck, Marie-Cecile Legdeur, Matthias Theobald, Emanuel Jacky, Mario Bargetzi, Johan Maertens, Gert Jan Ossenkoppele, Bob Löwenberg
Journal: Blood (2012)
The teleological science of self-control
Authors: Howard Rachlin
Journal: Behavioral and Brain Sciences (1997)

In response to Ainslie & Gault: The value of a temporally extended behavioral pattern depends on relationships inherent in the pattern itself. It is not possible to express that value as the simple sum of the discounted present values of the pattern's component acts.In response to Leiber: Teleological behaviorism may be deemed unscientific because it has not yet succeeded to the required degree in predicting and controlling the highly complex patterns of human behavior that comprise our mental lives. However teleological behaviorism is not unscientific because it is teleological or "noncausal;" nor is teleological behaviorism unscientific because it is not reducible to neurophysiology. Nothing in principle bars the development of a teleological science of the mind.
Complexity of antigenic determinants and humoral responses in vascular injury
Authors: O THAUNAT, G CALIGIURI, A NICOLETTI, J MICHEL
Journal: Cardiovascular Research (2005)

Circulating antibodies, reacting with autoantigens in the vascular wall, are commonly harmless in healthy vessels but can turn pathogenic in the presence of vascular injury.The exact antigenic determinants and the role of such autoreactive antibodies remain unclear.In their present study appearing in this issue, Shinohara and coworkers [1] propose a xenogenic, vaccinal experimental approach in order to limit intimal proliferation in response to balloon-induced arterial wall injury in rabbits.Their observations suggest that the observed humoral response is responsible for the limitation of smooth muscle cell (SMC) migration and proliferation via an extracellular effect on the SMC response to growth factors and angiotensin II, as observed in vitro.While the involvement of autoreactive antibodies in human autoimmune diseases and their vascular targeting are beyond the scope of the present editorial, the observations of Shinohara and coworkers merit some comments.The authors [1] used a mixture of specific and non-specific cellular xenoantigens shared by cultured rat SMC rendered inert for immunization.They also used a homogenized rabbit SMC preparation, including membrane-exposed and intracellular antigens, for exploring the autoreactive determinants of the response.Therefore, a precise identification of the molecular targets of the humoral response is difficult to evaluate.The presence of auto-antibodies, within the intima in vivo, was not presented in the study; nevertheless, the induced antibodies did not provoke apoptosis of SMC in vitro.One interesting point is that the humoral response
Lymphadenectomy in Apparent Early-Stage Endometrial Carcinoma: Do Numbers Count?
Authors: Carien L. Creutzberg
Journal: Journal of Clinical Oncology (2005)

Endometrial carcinoma is the most common gynecologic malignancy in Western countries, with an overall annual incidence in the United States of 25 per 100,000, increasing to more than 85 per 100,000 in women 60 years or older. Because the majority of patients present with early-stagedisease,theprognosisofendometrialcarcinoma patients is generally good, with 5-year overall and cancerspecific survival rates of 80% to 85% and 90% to 95%. 1-4 Endometrial carcinoma is primarily a cancer of postmenopausalwomen,withconcurrentmorbiditiessuchasobesity, hypertension, and diabetes. Given the favorable outcome for the majority of cases, the challenge is to effectively select those patients at increased risk of relapse who might benefit from more extensive surgical procedures and adjuvant therapies, and to avoid overtreatment of low-risk cases that would be exposed unnecessarily to the risk of excess morbidity. Since the Gynecologic Oncology Group (GOG)-33 staging study, 5,6 which reported an overall 9% risk of pelvic lymph node metastases in clinical stage I endometrial cancer (25% for cases with outer-third myometrial invasion and 18% for grade 3 disease), gynecologic oncologists have advocated standard lymphadenectomy or sampling proceduresforallintermediate-andlow-riskendometrialcancer patients. It should be noted that GOG-33 included 12% patients, who at laparotomy were found to have macroscopic extrauterine disease; of these, 51% had pelvic metastases, and 23% had aortic node metastases. Among the patients without gross intraperitoneal spread, only 7% and 4% had positive pelvic or aortic nodes, respectively. Women at high risk ( 10%) for pelvic node metastasis were those with grade 3 and outer-third invasion, while all other cases had low to moderate ( 5% to 10%) risk. 6 This is in accordance with the COSA-NZ-UK trial, 7 which re
Prostate-Specific Antigen and Premalignant Change: Implications for Early Detection
Authors: M. K. Brawer, P. H. Lange
Journal: CA A Cancer Journal for Clinicians (1989)

PSA represents a major advance in our tumor marker armamentarium. PIN fulfills the majority of requirements for a premalignant change. If we could determine a subset of individuals with PIN, an enriched population on which to base screening studies would emerge. In this regard the observation that PIN may be associated with elevation of the serum PSA is particularly intriguing. Considerable interest exists for early detection of prostate cancer. The high morbidity and mortality associated with this tumor coupled with the late stage at presentation by conventional means underscore the justification for such enthusiasm. However, the wisdom of screening for a cancer for which the mortality is far less than the histologic incidence remains to be proven. In the final analysis, the question is not whether we can detect more carcinoma, but rather whether we can significantly decrease patient morbidity and mortality. Until prospective randomized clinical trials demonstrate the effectiveness of early detection programs for carcinoma of the prostate, it is difficult to recommend such screening to the general public.
Two months follow up of auto-CPAP treatment in patients with obstructive sleep apnoea
Authors: A Boudewyns, V Grillier-Lanoir, M J Willemen, W A De Cock, P H Van de Heyning, W A De Backer
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Continuous positive airway pressure (CPAP) with fixed mask pressure is the current standard treatment for obstructive sleep apnoea (OSA). Auto-CPAP devices apply at any time the minimally required pressure to normalise breathing and may improve patient comfort and compliance. We present an open descriptive study of auto-CPAP treatment at home in patients previously managed with conventional CPAP. <h3>METHODS</h3> Fifteen patients with obstructive sleep apnoea (OSA), previously treated for at least one year with standard CPAP, were followed prospectively for a two month period on auto-CPAP. Outcome measures were both subjective evaluation by the patients and objective (polysomnographic) data obtained at one and two months of follow up. <h3>RESULTS</h3> The Epworth sleepiness score did not change significantly between baseline and follow up after one and two months and no systematic changes in CPAP related side effects were reported. Compared with the baseline polysomnographic values without treatment, a significant improvement in both respiratory and sleep parameters was observed during auto-CPAP. These results were not significantly different from those obtained with standard CPAP. A significant correlation was found between the effective CPAP pressure (Peff) and the amount of time spent below Peff during auto-CPAP treatment (<i>r</i> = 0.6, p = 0.01). <h3>CONCLUSION</h3> Long term auto-CPAP treatment in these patients with severe OSA appears to provide comparable efficacy to that of standard CPAP treatment.
The Breast Screening Programme and misinforming the public
Authors: Peter C Gøtzsche, Karsten Juhl Jørgensen
Journal: Journal of the Royal Society of Medicine (2011)

The information provided to the public by the NHS Breast Screening Programme has been criticized for lack of balance, omission of information on harms and substantially exaggerated estimates of benefit. These shortcomings have been particularly evident in the various invitation leaflets for breast screening and in the Programme's own 2008 Annual Review, which celebrated 20 years of screening. The debate on screening has been heated after new data published in the last two years questioned the benefit and documented substantial harm. We therefore analysed whether the recent debate and new pivotal data about breast screening has had any impact on the contents of the new 2010 leaflet and on the 2010 Annual Review. We conclude that spokespeople for the Programme have stuck to the beliefs about benefit that prevailed 25 years ago. Concerns about over-diagnosis have not been addressed either and official documents still downplay this most important harm of breast cancer screening.
Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells
Authors: Teresa Troiani, Erika Martinelli, Stefania Napolitano, Donata Vitagliano, Loreta Pia Ciuffreda, Sara Costantino, Floriana Morgillo, Anna Capasso, Vincenzo Sforza, Anna Nappi, Raffaele De Palma, Elena D'Aiuto, Liberato Berrino, Roberto Bianco, Fortunato Ciardiello
Journal: Clinical Cancer Research (2013)

Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance.We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab.Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET-dependent pathways, which were upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was detected in GEO-CR cells. A second colorectal cancer cell line with acquired resistance to cetuximab was obtained (SW48-CR). Inhibition of MET expression by siRNA restored cetuximab sensitivity in GEO-CR and SW48-CR cells, whereas exogenous activation of MET by HGF stimulation in cetuximab-sensitive GEO and SW48 cells induced resistance to cetuximab. Treatment of GEO-CR and SW48-CR cells with PHA665752, a selective MET inhibitor, inhibited cell growth, proliferation, and survival signals and impaired cancer cell migration. Overexpression of TGF-α, a specific EGFR ligand, was involved in the acquisition of cetuximab resistance in GEO-CR and SW48-CR cells. In fact, TGF-α overexpression induced the EGFR-MET interaction, with subsequent MET phosphorylation and activation of MET downstream effectors in GEO-CR and SW48-CR cells.These results suggest that overexpression of TGF-α through induction of EGFR-MET interaction contributes to cetuximab resistance in colorectal cancer cells. The combined inhibition of EGFR and MET receptor could represent a strategy for preventing and/or overcoming cetuximab resistance in patients with colorectal cancer.
Slow Down and Survive: Enigmatic Immunoregulation by BTLA and HVEM
Authors: Theresa L. Murphy, Kenneth M. Murphy
Journal: Annual Review of Immunology (2010)

B and T lymphocyte associated (BTLA) is an Ig domain superfamily protein with cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Its ligand, herpesvirus entry mediator (HVEM), is a tumor necrosis factor receptor superfamily member. The unique interaction between BTLA and HVEM allows for a system of bidirectional signaling that must be appropriately regulated to balance the outcome of the immune response. HVEM engagement of BTLA produces inhibitory signals through SH2 domain-containing protein tyrosine phosphatase 1 (Shp-1) and Shp-2 association, whereas BTLA engagement of HVEM produces proinflammatory signals via activation of NF-kappaB. The BTLA-HVEM interaction is intriguing and quite complex given that HVEM has four other ligands that also influence immune responses, the conventional TNF ligand LIGHT and lymphotoxin alpha, as well as herpes simplex virus glycoprotein D and the glycosylphosphatidylinositol-linked Ig domain protein CD160. BTLA-HVEM interactions have been shown to regulate responses in several pathogen and autoimmune settings, but our understanding of this complex system of interactions is certainly incomplete. Recent findings of spontaneous inflammation in BTLA-deficient mice may provide an important clue.
Germline <i>BRCA</i> Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma
Authors: Spring Holter, Ayelet Borgida, Anna Dodd, Robert Grant, Kara Semotiuk, David Hedley, Neesha Dhani, Steven Narod, Mohammad Akbari, Malcolm Moore, Steven Gallinger
Journal: Journal of Clinical Oncology (2015)

Purpose The main purpose of this study was to determine the prevalence of pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based cohort of patients with pancreatic ductal adenocarcinoma and describe the clinical and family history characteristics. Patients and Methods Unselected, consecutive, incident patients with pancreatic ductal adenocarcinoma were recruited at a single cancer center over a 2-year period. Participants provided blood for DNA analysis and cancer family history, and cancer treatment records were reviewed. DNA from all patients was analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification for germline variants in BRCA1 and BRCA2. Results Three hundred six patients were eligible for analysis. Pathogenic germline BRCA mutations were identified in 14 patients (4.6%; 95% CI, 2.2% to 6.9%), including 11 patients with a BRCA2 mutation and three patients with a BRCA1 mutation. Having a cancer family history that met genetic testing criteria of the National Comprehensive Cancer Network or the Ontario Ministry of Health and Long-Term Care or self-reporting as Ashkenazi Jewish was significantly associated with BRCA mutation carrier status (P = .02, P &lt; .001, and P = .05, respectively). However, the majority of the BRCA mutation–positive patients did not actually meet these genetic testing criteria. Conclusion Pathogenic BRCA mutations were identified in 4.6% of a large cohort of clinic-based patients. Considering the implications for family members of BRCA carriers, and possibly tailored chemotherapeutic treatment of patients, our finding has implications for broader BRCA genetic testing for patients with pancreatic ductal adenocarcinoma.
Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
Authors: Ethan J. Anderson, Mary E. Lustig, Kristen E. Boyle, Tracey L. Woodlief, Daniel A. Kane, Chien-Te Lin, Jesse W. Price, Li Kang, Peter S. Rabinovitch, Hazel H. Szeto, Joseph A. Houmard, Ronald N. Cortright, David H. Wasserman, P. Darrell Neufer
Journal: Journal of Clinical Investigation (2009)

High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H2O2-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H2O2 emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial H2O2 emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity.