tbuckley/cabot-search huggingface dataset:
Signaling of Kinesthetic Information by Peripheral Sensory Receptors
Authors: P R Burgess, J Y Wei, F J Clark, J Simon
Journal: Annual Review of Neuroscience (1982)

The relative position of our skeletal body parts is determined by the angles of our joints. In the absence of visual cues, joint angle information becomes conscious through a mental image of our body (body image). Introspective attention to the body image indicates that we have the following sensory information concerning a particular joint: knowledge of 1. the angle both when the joint is moving and stationary, and an awareness of 2. the direc­ tion and 3. the speed of angular changes. These three types of information can vary independently (e.g. a given position can be reached by movements
Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis
Authors: Larysa V. Yuzefovych, Andrea G. Kahn, Michele A. Schuler, Lars Eide, Ritu Arora, Glenn L. Wilson, Ming Tan, Lyudmila I. Rachek
Journal: Cancer Research (2016)

Abstract Production of mitochondrial reactive oxygen species and integrity of mitochondrial DNA (mtDNA) are crucial in breast cancer progression and metastasis. Therefore, we evaluated the role of mtDNA damage in breast cancer by genetically modulating the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the PyMT transgenic mouse model of mammary tumorigenesis. We generated mice lacking OGG1 (KO), mice overexpressing human OGG1 subunit 1α in mitochondria (Tg), and mice simultaneously lacking OGG1 and overexpressing human OGG1 subunit 1α in mitochondria (KO/Tg). We found that Tg and KO/Tg mice developed significantly smaller tumors than KO and wild-type (WT) mice after 16 weeks. Histologic analysis revealed a roughly 2-fold decrease in the incidence of lung metastases in Tg mice (33.3%) compared to WT mice (62.5%). Furthermore, lungs from Tg mice exhibited nearly a 15-fold decrease in the average number of metastatic foci compared with WT mice (P ≤ 0.05). Primary tumors isolated from Tg mice also demonstrated reduced total and mitochondrial oxidative stress, diminished mtDNA damage, and increased mitochondrial function. Targeting hOGG1 to the mitochondria protected cells from mtDNA damage, resulting in downregulation of HIF1α and attenuated phosphorylation of Akt. Collectively, we demonstrate proof of concept that mtDNA damage results in breast cancer progression and metastasis in vivo. Moreover, our findings offer new therapeutic strategies for modulating the levels of mtDNA repair enzymes to delay or stall metastatic progression. Cancer Res; 76(1); 30–34. ©2015 AACR.
Health authority tries to reclaim 700 000 settlement
Authors: C. Dyer
Journal: BMJ (1997)

A health authority is to take the unprecedented step of trying to reclaim the £700000 ($1.12m) settlement that it agreed to make to a severely disabled 9 year old girl a week before she died suddenly.

The settlement for Hollie Calladine was agreed by Nottingham Health Authority and incorporated in a court order by the consent of both parties on 19 May. On 27 May she died of respiratory cardiac arrest.

Paul Balen, the family's solicitor, said: “A …
DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer
Authors: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Hella Danø, Martin Berg, Ingelise Jensen, Anders Navrsted Pedersen, Sune Jürg Zimmermann, Hans-Jürgen Brodersen, Marie Overgaard, Jens Overgaard
Journal: Journal of Clinical Oncology (2015)

It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer.In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat.A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease.In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer.
Miscellaneous Item
Authors: W E Stehbens
Journal: Cardiovascular Research (1997)

Citing three histories involving berry, oncotic and w x atherosclerotic aneurysms Weber 1 recently introduced w x Herron's proposal 2 that proteolytic digestion was responsible for the aneurysms and associated renal cysts, diverticula, mitral valve prolapse and hernia.Aneurysms develop when intravascular pressure is greater than the wall can withstand, and as blood pressure never approaches levels necessary to rupture healthy arteries or veins, aneurysms indicate mural weakness.Aneurysms are not specific diseases but pathological dilatations complicating many diseases each with individualistic pathogenesis w x 3 .A common pathogenesis cannot be assumed.The outmoded congenital theory of cerebral aneurysms w x was based on assumption and fallacious evidence 4 .The initial mural atrophy and florid aneurysms are acquired w x and reproducible experimentally by hemodynamics 5,6 .This is facilitated by hypertension and lathyrism which are w x predisposing factors, not prerequisites 6 .Similarly hypertension and connective tissue disorders predispose to premature vascular fragility and human berry aneurysms which w x are acquired 3 .They complicate aortic coarctation and adult renal polycystic disease, both occurring with hypertension, although in the former the water hammer pulse of aortic valve insufficiency is contributory as in afferent w x arteries of arteriovenous shunts 3 .No scientific evidence suggests that the preceding mural atrophy or berry aneurysms are attributable to protease activity.Adult polycystic renal disease is purportedly an epithelial rather than a connective tissue disorder.Cyst dilatation results from excess epithelial production of cyst fluid without adequate drainage.Increasing intracyst pressure causes dilatation possibly aggravated by hemorrhage.Dilatation ceases when epithelial cells cease producing cyst fluid against intracystic pressure.Assuming enzymatic degradation of interstitial and perirenal connective tissue, tubular dilatation would require reduced or negative interstitial pressure which has no pathological basis.
The National Cardiovascular Data Registry Voluntary Public Reporting Program
Authors: Gregory J. Dehmer, Jonathan Jennings, Ruth A. Madden, David J. Malenka, Frederick A. Masoudi, Charles R. McKay, Debra L. Ness, Sunil V. Rao, Frederic S. Resnic, Michael E. Ring, John S. Rumsfeld, Marc E. Shelton, Michael C. Simanowith, Lara E. Slattery, William S. Weintraub, Ann Lovett, Sharon-Lise Normand
Journal: Journal of the American College of Cardiology (2015)
Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With <sup>18</sup> F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography
Authors: María N. Pizzi, Albert Roque, Nuria Fernández-Hidalgo, Hug Cuéllar-Calabria, Ignacio Ferreira-González, María T. Gonzàlez-Alujas, Gerard Oristrell, Laura Gracia-Sánchez, Juan J. González, José Rodríguez-Palomares, Manuel Galiñanes, Olga Maisterra-Santos, David Garcia-Dorado, Joan Castell-Conesa, Benito Almirante, Santiago Aguadé-Bruix, Pilar Tornos
Journal: Circulation (2015)

Background— The diagnosis of infective endocarditis (IE) in prosthetic valves and intracardiac devices is challenging because both the modified Duke criteria (DC) and echocardiography have limitations in this population. The added value of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18 F-FDG PET/CT angiography (PET/CTA) was evaluated in this complex scenario at a referral center with a multidisciplinary IE unit. Methods and Results— Ninety-two patients admitted to our hospital with suspected prosthetic valve or cardiac device IE between November 2012 and November 2014 were prospectively included. All patients underwent echocardiography and PET/CT, and 76 had cardiac CTA. PET/CT and echocardiography findings were evaluated and compared, with concordant results in 54% of cases (κ=0.23). Initial diagnoses with DC at admission, PET/CT, and DC+PET/CT were compared with the final diagnostic consensus reached by the IE Unit. DC+PET/CT enabled reclassification of 90% of cases initially classified as possible IE with DC and provided a conclusive diagnosis (definite/rejected) in 95% of cases. Sensitivity, specificity, and positive and negative predictive values were 52%, 94.7%, 92.9%, and 59.7% for DC; 87%, 92.1%, 93.6%, and 84.3% for PET/CT; and 90.7%, 89.5%, 92%, and 87.9% for DC+PET/CT. Use of PET/CTA yielded even better diagnostic performance values than PET/nonenhanced CT (91%, 90.6%, 92.8%, and 88.3% versus 86.4%, 87.5%, 90.2%, and 82.9%) and substantially reduced the rate of doubtful cases from 20% to 8% ( P &lt;0.001). DC+PET/CTA reclassified an additional 20% of cases classified as possible IE with DC+PET/nonenhanced CT. In addition, PET/CTA enabled detection of a significantly larger number of anatomic lesions associated with active endocarditis than PET/nonenhanced CT ( P =0.006) or echocardiography ( P &lt;0.001). Conclusions— 18 F-FDG PET/CT improves the diagnostic accuracy of the modified DC in patients with suspected IE and prosthetic valves or cardiac devices. PET/CTA yielded the highest diagnostic performance and provided additional diagnostic benefits.
Targeting Cancer Stem Cells in Castration-Resistant Prostate Cancer
Authors: Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Elizabeth Hernandez, Ladan Fazli, Martin Gleave, Jer-Tsong Hsieh
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Clinical evidence suggests increased cancer stem cells (CSCs) in a tumor mass may contribute to the failure of conventional therapies because CSCs seem to be more resistant than differentiated tumor cells. Thus, unveiling the mechanism regulating CSCs and candidate target molecules will provide new strategy to cure the patients. Experimental design: The stem-like cell properties were determined by a prostasphere assay and dye exclusion assay. To find critical stem cell marker and reveal regulation mechanism, basic biochemical and molecular biologic methods, such as quantitative real-time PCR, Western blot, reporter gene assay, and chromatin immunoprecipitation assay, were used. In addition, to determine the effect of combination therapy targeting both CSCs and its progeny, in vitro MTT assay and in vivo xenograft model was used. Results: We demonstrate immortalized normal human prostate epithelial cells, appeared nontumorigenic in vivo, become tumorigenic, and acquire stem cell phenotype after knocking down a tumor suppressor gene. Also, those stem-like cells increase chemoresistance to conventional anticancer reagent. Mechanistically, we unveil that Wnt signaling is a key pathway regulating well-known stem cell marker CD44 by directly interacting to the promoter. Thus, by targeting CSCs using Wnt inhibitors synergistically enhances the efficacy of conventional drugs. Furthermore, the in vivo mouse model bearing xenografts showed a robust inhibition of tumor growth after combination therapy. Conclusions: Overall, this study provides strong evidence of CSC in castration-resistant prostate cancer. This new combination therapy strategy targeting CSC could significantly enhance therapeutic efficacy of current chemotherapy regimen only targeting non-CSC cells. Clin Cancer Res; 22(3); 670–9. ©2015 AACR.
High-dose cisplatin administration without hypertonic saline: observation of disabling neurotoxicity.
Authors: S S Legha, I W Dimery
Journal: Journal of Clinical Oncology (1985)

Nephrotoxicity of cisplatin can be ameliorated with intravenous (IV) hydration and forced diuresis with mannitol. Cisplatin has recently been used with hypertonic saline which allows administration of higher doses amounting to 40 mg/m2/d for 5 days, without significant nephrotoxicity. In this report we describe our experience with administration of cisplatin in a dose range of 30 to 40 mg/m2/d for 5 days, administered with IV hydration alone. Thirteen patients with recurrent carcinoma of the head and neck region were treated with high-dose cisplatin along with 5-fluorouracil (5-FU) used as a continuous infusion. Eight patients received a total of 21 courses of cisplatin with the higher dose range (40 mg/m2 for 5 days) and the remainder received 11 courses with the lower dose range. The renal toxicity was minimal but the myelo-suppression was intense, frequently requiring hospitalization for the treatment of infections associated with neutropenia. Furthermore, we encountered severe peripheral neuropathy in five patients, four of whom developed major difficulties with ambulation. Six patients achieved objective regression of their tumor, two had minor response, and five failed to respond to chemotherapy. The study was terminated because of serious nonrenal toxicity from the high-dose cisplatin. Based on our limited experience, we believe that IV hydration alone, without the use of hypertonic saline, allows administration of high-dose cisplatin without significant nephrotoxicity. However, cisplatin used in a dose schedule of 40 mg/m2 for 5 days for more than three courses resulted in a disabling form of peripheral neuropathy.
Technosphere Inhaled Insulin: Is Faster Better?
Authors: Jack L. Leahy
Journal: Diabetes Care (2015)

Pulmonary-delivered insulin is again a reality (1). The failure of the first inhaled insulin in 2007 showed that being radically different from what health care providers are used to, even when injections are avoided, can be problematic. The current product Technosphere inhaled insulin has addressed many of the prior concerns—a more convenient delivery device that is dosed in insulin units. Also, fear of lung toxicity or tumor development has been lessened somewhat by in vitro cytotoxic (2) and in vivo clearance (3) studies, plus a 2-year clinical trial showed no differences in pulmonary imaging or function in Technosphere-treated and untreated subjects with diabetes (4). In addition, aerosolized medicines that have effective absorption into the bloodstream are well established (5), with numerous agents having been tried including glucagon-like peptide 1 (6).

A highly touted feature of pulmonary-delivered insulin is its rapid absorption—peak absorption by 10–15 min and fully cleared by 2–3 h versus a peak of 45–60 min and clearance of 5–6 h for injected analog prandial insulins (1,7) (Fig. 1). The potential importance of an ultrafast “on response” relates to the phasic nature of endogenously secreted insulin. An intravenous glucose infusion in humans without diabetes elicits a distinct first phase of insulin secretion over the first 10 min that is followed by a short lull and then a sustained second phase for the duration of the hyperglycemia. Actually, the diverse nutrient makeup of meals and their oral delivery initiate a more broad-based insulin response that does not separate into distinct phases. Still, the early insulin that is secreted …
Cushing’s Syndrome Due to CRH and ACTH Co-secreting Pancreatic Tumor—Presentation of a New Case Focusing on Diagnostic Pitfalls
Authors: Athanasios Fountas, Zoe Giotaki, Nikos Ligkros, Efthymia D. Tsakiridou, Stelios Tigas, Wolfgang Saeger, Agathocles Tsatsoulis
Journal: Endocrine Pathology (2015)
Comment on Juraschek et al. Cardiorespiratory Fitness and Incident Diabetes: The FIT (Henry Ford ExercIse Testing) Project. Diabetes Care 2015;38:1075–1081
Authors: Benno Krachler, Bernt Lindahl
Journal: Diabetes Care (2015)

Comment on Juraschek et al. Cardiorespiratory Fitness and Incident Diabetes : The FIT (Henry Ford ExercIse Testing) Project. Diabetes Care 2015;38:1075-1081
Invertebrate Learning and Memory: From Behavior to Molecules
Authors: T J Carew, C L Sahley
Journal: Annual Review of Neuroscience (1986)

Classical ethologists have provided a long and rich tradition of stud ying the learning and memory capabilities of a variety of invertebrate animals (Schneirla 1929, von Frisch 1950, Lindauer 1960). In recent years, however, interest in this field has been renewed because it has become clear that many invertebrate animals can provide powerful model systems in which to explore the cellular and molecular mechanisms of learning and memory. Thus, a variety of disciplines such as neuroethology, psychology, and modern neurobiology have merged in a concerted effort to develop invertebrate preparations in which these combined approaches can be focused on the general theme of the cellular basis of behavioral plasticity. This overall strategy has come to be known as a simple-systems approach to the study of learning and memory. A simple-systems approach is not the exclusive domain of invertebrate research. The general strategy of such an approach is to try to identify neural circuits involved in a particular form oflearning and then attempt to specify the precise locus and nature of the cellular changes that are involved. This approach has been successfully applied in a number of vertebrate systems. These include eyeblink conditioning in the cat (Kim et al 1983, Woody et a1 1983, Woody 1984), cardiac conditioning in the pigeon (Cohen 1980, 1984), and conditioning of the nictitating membrane response in rabbit (Thompson et a1 1983, 1984, Moore et a1 1982, Harvey et aI 1985), as well as cellular analog systems in cerebellum (Ito 1982), the red nucleus (Tskahara, 1984), and hippocampus (McNaughton et al 1 978, Levy &
Similar virus spectra and seasonality in paediatric patients with acute respiratory disease, Ghana and Germany
Authors: A. Annan, F. Ebach, V.M. Corman, R. Krumkamp, Y. Adu-Sarkodie, A.M. Eis-Hübinger, T. Kruppa, A. Simon, J. May, J. Evans, M. Panning, C. Drosten, J.F. Drexler
Journal: Clinical Microbiology and Infection (2015)
Pathophysiological Basis of Vulnerability to Drug Abuse: Role of an Interaction Between Stress, Glucocorticoids, and Dopaminergic Neurons
Authors: P V Piazza, M L Le Moal
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some individuals to respond in a pathophysiological way to drugs.
Phase I, dose-escalation, clinical trial of MVA-Brachyury-TRICOM vaccine demonstrating safety and brachyury-specific T cell responses
Authors: Christopher R Heery, Renee Donahue, Lauren Lepone, Italia Grenga, Jacob Richards, Simon Metenou, Romaine I Fernando, Ulrike Dirmeier, Harpreet Singh, Ravi Madan, James L Gulley, Jeffrey Schlom
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Brachyury is a tumor-associated antigen and transcription factor that drives the epithelial-to-mesenchymal transition in human carcinomas. This Phase I study assessed whether patients with advanced cancer or chordoma, a rare tumor of the notochord that overexpresses brachyury, can
Circulating free DNA concentration is an independent prognostic biomarker in lung cancer
Authors: Claire Tissot, Anne-Claire Toffart, Stéphanie Villar, Pierre-Jean Souquet, Patrick Merle, Denis Moro-Sibilot, Maurice Pérol, Jiri Zavadil, Christian Brambilla, Magali Olivier, Sébastien Couraud
Journal: European Respiratory Journal (2015)

Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies with larger sample sizes and including patients who receive more homogenous treatments. Our objective was to assess the predictive and prognostic value of plasma cfDNA concentration in a large series of patients with NSCLC and treated with a standard chemotherapy regimen. We included samples from lung cancer patients recruited into the Pharmacogenoscan study. The cfDNA of 218 patients was extracted and quantified by fluorometry before and after two or three cycles of platinum-based chemotherapy. The association between baseline and post-chemotherapy concentrations and treatment response, assessed by RECIST (response evaluation criteria in solid tumours) or patient survival was analysed. Patients with high cfDNA concentrations (highest tertile) at baseline had a significantly worse disease-free and overall survival than those with lower concentrations (lowest and middle tertiles) (median overall survival 10 months (95% CI 10.7–13.9) versus 14.2 months (95% CI 12.6–15.8), respectively; p=0.001). In multivariate analysis, increased baseline concentration of cfDNA was an independent prognostic factor. However, we did not find any association between cfDNA concentration and response to treatment. cfDNA may be a biomarker for the assessment of prognosis in NSCLC. However, total concentration of cfDNA does not appear to predict chemotherapy response.