tbuckley/cabot-search huggingface dataset:
A novel Dance Dance Revolution (DDR) system for in-home training of stepping ability: basic parameters of system use by older adults
Authors: S T Smith, C Sherrington, S Studenski, D Schoene, S R Lord
Journal: British Journal of Sports Medicine (2009)

Objective This series of studies was conducted to develop and establish characteristics of exercise videogame play in older adults. The videogame was a modified version of the popular Dance Dance Revolution (DDR; Konomi). Methods Participants aged ≥70 were asked to make simple step movements in response to vertically drifting arrows presented on a video screen. Step responses were detected by a modified USB DDR mat, and characteristics of stepping performance such as step timing, percentage of missed target steps and percentage of correct steps were recorded by purpose-built software. Drift speed and step rate of visual stimuli were modified to increase task difficulty. Results Significant linear relationships between stepping performance and stimulus characteristics were observed. Performance of older adults decreased as stimulus speed and step rate were increased. Optimal step performance occurred for a stimulus speed of 17° of visual angle per second and a step rate of one step every 2 s. At fast drift speeds (up to 35°/s), participants were more than 200 ms too slow in coordinating their steps with the visual stimulus. Younger adults were better able to perform the stepping task across a wider range of drift speeds than older adults. Conclusion The findings suggest that older adults are able to interact with video games based upon DDR but that stepping performance is determined by characteristics of game play such as arrow drift speed and step rate. These novel “exergames” suggest a low-cost method by which older adults can be engaged in exercises that challenge balance and which can be conducted in their own homes.
Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin
Authors: B Falini, L Flenghi, F Aversa, G Barbabietola, M.F Martelli, P Comeli, P.L Tazzari, M.K Broe, H Stein, H Dürkop, G Pizzolo, A Bolognesi, F Stirpe, E Sabattini, S Pileri
Journal: The Lancet (1992)
Measurement of Insulin Sensitivity in Children
Authors: Betsy Schwartz, David R. Jacobs, Antoinette Moran, Julia Steinberger, Ching-Ping Hong, Alan R. Sinaiko
Journal: Diabetes Care (2008)

OBJECTIVE—In this study we compared fasting insulin and measures of insulin sensitivity (M) based on fasting insulin and glucose (i.e., homeostasis model assessment [HOMA], quantitative insulin sensitivity check index [QUICKI], and fasting glucose–to–insulin ratio [FGIR]) or triglycerides to the insulin clamp in a cohort of children/adolescents. RESEARCH DESIGN AND METHODS—The subjects were Minneapolis fifth- to eighth-grade students. Euglycemic-hyperinsulinemic clamps were performed on 323 adolescents at mean age 13 and were repeated on 300 of these subjects at mean age 15. Insulin sensitivity was determined by glucose uptake (milligrams per kilogram per minute) adjusted for lean body mass (MLBM) and steady-state insulin (MLBM/ln SSI). Comparisons were made for the whole cohort and by body size (BMI &amp;lt;85th percentile vs. BMI ≥85th percentile). Receiver operating characteristic (ROC) curves were used to test whether specific fasting insulin cut points separated true-positive from false-positive approximations of insulin resistance. RESULTS—Fasting insulin was significantly correlated with HOMA (r = 0.99), QUICKI (r = 0.79), FGIR (r = −0.62), and (ln fasting insulin + ln triglycerides) (r = 0.88). Correlations of the surrogates with MLBM were significantly lower than those with M for the total cohort and ≥85th percentile group. In general, correlations in the ≥85th percentile group were higher than those in the &amp;lt;85th percentile group. Correlations with MLBM and MLBM/ln SSI decreased in the total cohort and ≥85th percentile group from age 13 to 15. ROC curves showed only a modest capability to separate true- from false-positive values. CONCLUSIONS—Surrogate measures are only modestly correlated with the clamp measures of insulin sensitivity and do not offer any advantage over fasting insulin. In general, lower correlations are seen with MLBM than with M and with thinner than with heavier individuals.
Overexpression of miR-200c Induces Chemoresistance in Esophageal Cancers Mediated Through Activation of the Akt Signaling Pathway
Authors: Rie Hamano, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Johji Hara, Jeong ho Moon, Kiyokazu Nakajima, Shuji Takiguchi, Yoshiyuki Fujiwara, Masaki Mori, Yuichiro Doki
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To determine the relationship between resistance to chemotherapy and microRNA (miRNA) expression in esophageal cancer, we focused on miRNAs known to be associated with maintenance of stem cell function. Experimental Design: Using 98 formalin-fixed, paraffin-embedded samples obtained from patients with esophageal cancer who had received preoperative chemotherapy followed by surgery, we measured expression levels of several miRNAs that are considered to be involved in the regulation of stem cell function (e.g., let-7a, let-7g, miR-21, miR-134, miR-145, miR-155, miR-200c, miR-203, and miR-296) by real-time reverse transcriptase PCR. Then, we examined the relationship between miRNA expression and prognosis or response to chemotherapy. To investigate the mechanism of miRNA-induced chemoresistance, in vitro assays were carried out using esophageal cancer cells. Results: Analyses of the 9 miRNAs expression showed that overexpression of miR-200c (P = 0.037), underexpression of miR-145 (P = 0.023), and overexpression of miR-21 (P = 0.048) correlated significantly with shortened overall duration of survival. In particular, miR-200c expression correlated significantly with response to chemotherapy (P = 0.009 for clinical response; P = 0.007 for pathologic response). In vitro assay showed significantly increased miR-200c expression in cisplatin-resistant cells compared with their parent cells (∼1.7-fold). In anti-miR-200c–transfected cells, chemosensitivity to cisplatin and apoptosis after exposure to cisplatin was found to increase as compared with the negative control. Western blotting showed that knockdown of miR-200c expression was associated with increased expression of PPP2R1B, a subunit of protein phosphatase 2A, which resulted in reduced expression of phospho-Akt. Conclusions: Results of this study emphasized the involvement of miR-200c in resistance to chemotherapy among esophageal cancers and that this effect was mediated through the Akt pathway. Clin Cancer Res; 17(9); 3029–38. ©2011 AACR.
Matrix metalloproteinase-3–dependent generation of a macrophage chemoattractant in a model of herniated disc resorption
Authors: Hirotaka Haro, Howard C. Crawford, Barbara Fingleton, John R. MacDougall, Kenichi Shinomiya, Dan M. Spengler, Lynn M. Matrisian
Journal: Journal of Clinical Investigation (2000)

Herniated disc (HD) is a common health problem that is resolved by surgery unless spontaneous resorption occurs. HD tissue contains abundant macrophage infiltration and high levels of matrix metalloproteinases (MMPs) MMP-3 and MMP-7. We developed a model system in which disc tissue or isolated chondrocytes from wild-type or MMP-null mice were cocultured with peritoneal macrophages and used this system to investigate the role of MMPs and chondrocyte/macrophage interactions in disc resorption. We observed a marked enhancement of MMP-3 protein and mRNA in chondrocytes after exposure to macrophages. Chondrocytic MMP-3, but not MMP-7, was required for disc resorption, as determined by assaying for a reduction in wet weight and proteoglycan content after 3 days of coculture. Surprisingly, chondrocyte MMP-3 was required for the generation of a macrophage chemoattractant and the subsequent infiltration of the disc tissue by proteolytically active macrophages. We conclude that macrophage induction of chondrocyte MMP-3 plays a major role in disc resorption by mechanisms that include the generation of a bioactive macrophage chemoattractant.
Catecholamine-induced myocardial potassium uptake mediated by beta 1-adrenoceptors and adenylate cyclase activation in the pig.
Authors: O Ellingsen, O M Sejersted, S Leraand, A Ilebekk
Journal: Circulation Research (1987)

The myocardial potassium uptake during intracoronary isoproterenol stimulation was characterized in 12 anesthetized pigs. The beta-receptor subtype specificity and the effect of adenylate cyclase activation were determined. Potassium concentrations were continuously recorded by PVC-valinomycin minielectrodes in the left atrial cavity and in coronary sinus blood diverted through a shunt to the right atrium. The difference in potassium concentration between the left atrial cavity and coronary sinus, and the accumulated myocardial potassium uptake were calculated after computerized data sampling. By intracoronary drug infusion, changes in heart rate and systemic effects were minimized. Isoproterenol (0.6-0.8 microgram/min), a nonspecific beta-agonist, reduced coronary sinus potassium concentration transiently to a nadir of 0.28 (0.15-0.43) mM (median and 95% confidence interval) below control values (n = 12). The potassium uptake, which amounted to 140 (79-202) mumol/100 g tissue, corresponding to an intracellular potassium increase of about 3 mM, was abolished after selective beta 1-blockade by pafenolol. The specific beta 1-agonist dobutamine (40 micrograms/min) caused a similar potassium uptake before and after selective beta 2-blockade by ICI 118, 551. Salbutamol (2 micrograms/min), a specific beta 2-agonist, induced a minor potassium uptake of 4 (1-20) mumol/100 g, blocked by pafenolol. After nonselective beta-blockade by propranolol the adenylate cyclase stimulator forskolin caused a myocardial potassium uptake of similar magnitude to that of isoproterenol before beta-blockade. We conclude that a myocardial potassium uptake ensues during beta 1-adrenoceptor stimulation and adenylate cyclase activation.
The Role of Computerized Tomography in the Diagnosis of Diseases of the Thorax
Authors: E. Robert Heitzman
Journal: JAMA (1979)

THE PURPOSE of this communication is to provide a preliminary evaluation of the diagnostic potential of computerized tomography (CT) of the thorax based on a review of approximately 300 examinations. Evens<sup>1</sup>has stated that CT of the body will probably have less diagnostic impact than has CT of the head. While this opinion may ultimately prove to be correct, it seems that a technique that can demonstrate visceral anatomy so well is certain to be of great value. Our experience with CT of the thorax leads us to be enthusiastic about the diagnostic potential of this modality. Respiratory and cardiac motion are often cited as factors that seriously compromise the quality of CT of the thorax, since they necessarily degrade the image, particularly when longer scan times are used.<sup>2</sup>While this point is incontestable, it has seemed to us that these factors are less limiting than might be anticipated.
NOTCH3 Signaling Pathway Plays Crucial Roles in the Proliferation of ErbB2-Negative Human Breast Cancer Cells
Authors: Noritaka Yamaguchi, Tetsunari Oyama, Emi Ito, Hitoshi Satoh, Sakura Azuma, Mitsuhiro Hayashi, Ken Shimizu, Reiko Honma, Yuka Yanagisawa, Akira Nishikawa, Mika Kawamura, Jun-ichi Imai, Susumu Ohwada, Kuniaki Tatsuta, Jun-ichiro Inoue, Kentaro Semba, Shinya Watanabe
Journal: Cancer Research (2008)

ErbB2-negative breast tumors represent a significant therapeutic hurdle because of a lack of effective molecular targets. Although NOTCH proteins are known to be involved in mammary tumorigenesis, the functional significance of these proteins in ErbB2-negative breast tumors is not clear. In the present study, we examined the expression of activated NOTCH receptors in human breast cancer cell lines, including ErbB2-negative and ErbB2-positive cell lines. Activated NOTCH1 and NOTCH3 proteins generated by gamma-secretase were detected in most of the cell lines tested, and both proteins activated CSL-mediated transcription. Down-regulation of NOTCH1 by RNA interference had little or no suppressive effect on the proliferation of either ErbB2-positive or ErbB2-negative cell lines. In contrast, down-regulation of NOTCH3 significantly suppressed proliferation and promoted apoptosis of the ErbB2-negative tumor cell lines. Down-regulation of NOTCH3 did not have a significant effect on the ErbB2-positive tumor cell lines. Down-regulation of CSL also suppressed the proliferation of ErbB2-negative breast tumor cell lines, indicating that the NOTCH-CSL signaling axis is involved in cell proliferation. Finally, NOTCH3 gene amplification was detected in a breast tumor cell line and one breast cancer tissue specimen even though the frequency of NOTCH3 gene amplification was low (<1%). Taken together, these findings indicate that NOTCH3-mediated signaling rather than NOTCH1-mediated signaling plays an important role in the proliferation of ErbB2-negative breast tumor cells and that targeted suppression of this signaling pathway may be a promising strategy for the treatment of ErbB2-negative breast cancers.
Pulmonary perspective: immunology in diagnosis and treatment of lung cancer
Authors: P Weynants, FX Marchandise, Y Sibille
Journal: European Respiratory Journal (1997)

The combination of the limits encountered with current therapies and the increased knowledge of immunology have opened perspectives for the use of immunomodulators in the management of lung cancer patients. Both humoral and cellular immunity are now evaluated in diagnosis and treatment of cancer. Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested with various imaging techniques to improve detection and staging of lung cancer. MoAbs are also used in therapeutic clinical trials as: 1) mediators of immune effector function; 2) carriers of cytotoxic agents; 3) agents to block tumour growth factor; or 4) anti-idiotype vaccines. Immune effector cells, such as natural killer (NK) cells, T- and B-lymphocytes, macrophages, dendritic cells and neutrophils, are present either within or around tumours and are likely to play a role in cancer. These cells, either alone or with cytokines, could provide new efficient therapeutic approaches, particularly if immunosuppression is involved in tumour progression. In this context, most recent studies using immune cells and molecular bioengineering, could provide additional antitumoral effects. Finally, the discovery of several tumour rejection antigens has revived the dream of designing tumour vaccines and active specific immunotherapy.
Drivers of violent conflict
Authors: Bradley A Thayer
Journal: Journal of the Royal Society of Medicine (2007)

Please e-mail letters for publication to Dr Kamran Abbasi [ kamran.abbasi@rsm.ac.uk ]. Letters should be no longer than 300 words and preference will be given to letters responding to articles published in the JRSM. Our aim is to publish letters quickly. Not all correspondence will be acknowledged.
Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer
Authors: David P. Kelsen, Katryn A. Winter, Leonard L. Gunderson, Joanne Mortimer, Norman C. Estes, Daniel G. Haller, Jaffer A. Ajani, Walter Kocha, Bruce D. Minsky, Jack A. Roth, Christopher G. Willett
Journal: Journal of Clinical Oncology (2007)

We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed.The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated.Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival.For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.
Pharmacologic Interruption of the Renin-Angiotensin System
Authors: N K Hollenberg
Journal: The Annual Review of Pharmacology and Toxicology (1979)

In 1 959, at a symposium on polypeptides that affect smooth muscle and blood vessels, Elliott recounted how, following elucidation of  structure of  decapeptide, angiotensin I, he set out to synthesize  agent and found that  synthetic product had only about I % of  activity of angiotensin II on rat blood pressure despite close chemical resemblance ( l). Elliott's key point in his talk was that  carboxy terminal amino acid, phenylalanine, contained almost equal mixtures of  0and L-forms. Given  freedom of a symposium setting, he went on to make  daring and perceptive speculation that the peptide containing o-phenylalanine was acting as a powerful inhibitor of hypertensin in vivo. He pointed out that proof required  unequivocal synthesis of a peptide containing pure o-phenylalanine, and expressed  hope that this would soon be achieved. Unfortunately, that synthesis was never reported and  importance of  carboxy terminal amino acid for  development of angiotensin antagonists was apparently forgotten for over a decade. Given  potential importance of pharmacologic interruption of  renin-angiotensin system in dissecting angiotensin'S role in physiology and pathophysiology,  failure of  discussion that followed  presentations on angiotensin to respond to Elliott's novel suggestion was surprising, and perhaps discouraging. In 1 970 two groups, Khairallah, Bumpus, and their colleagues at Cleve­ land Clinic Foundation and Marshall, Vine & Needleman in 8t. Louis
Just Say Die
Authors: Scott R. Berry
Journal: Journal of Clinical Oncology (2007)

As a medical oncologist, I spend most of my time treating people with incurable cancers. Depending on the person and the specific illness that person has, that question may come on the first visit with me or on the tenth: “How long have I got?” It may come out of the blue or as part of a larger discussion about the progress of their disease. I will say, “It may be only a few months until the end ” or “until you pass away, ” but I rarely say exactly what I mean: “It’s only going to be a few months until you die.” Die is a short, simple word. The problem is that I rarely use it when I speak to my dying patients, and I don’t think I’m alone. Quality end-of-life care is an ethical imperative, and improving conversations about the end-oflife is an important part of improving that care. Although it’s acknowledged that discussions about dying are important, little has been written about the words we use during these discussions. I would like to examine why it is so difficult for physicians to use the word “die,” and why it may be so important that we use it more often.
Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses
Authors: Pia Trip, Esther J. Nossent, Frances S. de Man, Inge A.H. van den Berk, Anco Boonstra, Herman Groepenhoff, Edward M. Leter, Nico Westerhof, Katrien Grünberg, Harm-Jan Bogaard, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2013)

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide ( D LCO ) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preserved D LCO . Retrospectively, 166 IPAH patients were included and grouped based on a D LCO cut-off value of 45% pred (IPAH &lt;45% and IPAH ≥45% ). Clinical characteristics, treatment responses and survival were compared. IPAH &lt;45% were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a low D LCO . Age and number of pack years were independently associated with D LCO &lt;45% pred. IPAH &lt;45% showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease. To conclude, a severely reduced D LCO in IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.