tbuckley/cabot-search huggingface dataset:
Tissue resident memory T cells create genetically distinct immune microenvironments within melanoma metastasis
Authors: Kavita Dhodapkar, Noffar Bar, Chandra Sekhar Boddupalli, Krishna Kadaveru, Zifeng Mai, Yanhong Deng, Mario Sznol, Madhav Dhodapkar
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Blockade of inhibitory immune checkpoints (ICPs) improves survival in melanoma patients. Interestingly, the expression of these ICPs in most tumor tissues including melanoma is restricted to only a subset of tumor-infiltrating immune cells (TIICs). Here, we utilize single cell
TWO CASES OF INOPERABLE SCIRRHUS OF THE BREAST TREATED BY OOPHORECTOMY: RESULTS
Authors: E. P. Paton
Journal: BMJ (1902)

THE X RAYS IS RECURRENT SOIRREUS.LMARCH It 190I left kidney, was a rent in the jejunum, near its commence- ment close to the spine, about x2 inch long in the longitudinal axis of the bowel, at its free border; the edges of this rent were thickened as if bruised; no other source of haemorrhage was discovered.
NHS culture depends on enlightened leadership and aligned incentives
Authors: Donald W Light
Journal: Journal of the Royal Society of Medicine (2008)

The recent article on ‘What the NHS needs to improve’ (JRSM 2008;101:7–11)1 identifies four valuable ingredients of a good culture but omits what is needed to achieve it. As a professor of comparative health care systems who has worked closely with many parts of the NHS since the Thatcher reforms, I think the answers are most clearly found in the transformation of the US Veterans Health Administration from a public, politicized system considerably worse than the NHS in the early 1990s to one considerably better that outperforms even the great medical centres. The key elements are a coherent master plan for patient-centred care that rewards quality and value for money, a strong and steady leadership to implement the plan at every level from regional to individual service design, the elimination of perverse incentives, and the construction of aligned incentives at every level.

Most of the costly and extensive reforms of the NHS I have witnessed since 1990 have been half-baked and partially contrary to the previous ones so that an accretion of crosscutting changes has developed. Powerful, perverse and non-aligned incentives undermine the development of cost-effective, integrated services. Leaders keep changing, and each new one asserts his or her presence by correcting or reversing previous initiatives and instigating new ones. Current initiatives – such as ‘payment by results’, which has nothing to do with payment by results but rather payment by activity – build in perverse incentives that will distort services in new ways. Until the economics and organisation of services support cost-effective, integrated services of quality for patients, a culture of Confidence, Compassion, Connectedness and Curiosity will not happen.
Limitations in daily activities are the major determinant of reduced health-related quality of life in patients with hand osteoarthritis
Authors: W. Y. Kwok, T. P. M. Vliet Vlieland, F. R. Rosendaal, T. W. J. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2010)

To determine the impact of limitations in daily activities and pain on quality of life (QoL) in patients with osteoarthritis (OA) visiting a rheumatologist.Patients diagnosed by the rheumatologist with primary hand, knee or hip OA were consecutively included from August 2005 to April 2009. QoL was assessed by Short Form-36, with the physical component summary score (PCS), calculated using data from a norm-based population. Self-reported pain and function in patients with hand OA was assessed by the Australian/Canadian OA hand index (AUSCAN) pain (range 0-20) and AUSCAN function (range 0-36). Linear regression analyses were performed to investigate associations between PCS and demographic characteristics, and between PCS and pain and function in patients with OA.Hand OA was diagnosed in 95% of 460 included patients (89% women, mean age 61 years). PCS was lowered in patients with OA. Patients with hand OA reported a considerable amount of pain (mean 9.5 (SD 4.3)) and disability (mean 16.5 (SD 8.6)). AUSCAN function was associated with PCS (adjusted β=-0.3, 95% CI -0.4 to -0.2), but AUSCAN pain was not.Hand OA was the most common OA subtype in secondary care. Health-related QoL is decreased in patients with OA and is associated with limitations in daily activities.
Spatial and Temporally Restricted Expression of Chemokines and Chemokine Receptors in the Developing Human Kidney
Authors: Hermann-Josef Gro[Combining Diaeresis]ne, Clemens D. Cohen, Elisabeth Gro[Combining Diaeresis]ne, Claudia Schmidt, Matthias Kretzler, Detlef Schlo[Combining Diaeresis]ndorff, Peter J. Nelson
Journal: Journal of the American Society of Nephrology (2002)

The directed migration of cells, cell-cell adhesion, and the control of proliferation are key events during metanephric development. The chemokines are a family of proteins that selectively control aspects of cell migration, activation, proliferation, and adhesion. The expression of a series of chemokines and chemokine receptors during human renal development was investigated by using immunohistochemical analyses and real-time reverse transcription-PCR assays of defined laser-microdissected metanephric structures. The results demonstrate that mononuclear cell-like cells within the nephrogenic blastema focally express interferon-inducible protein-10/CXCL10, a ligand for CXCR3. Mononuclear-like cells dispersed through the developing organ express CX(3)CR1. Expression of CXCR4, the receptor for stromal cell-derived factor-1/CXCL12, is also limited to stromal CD34-positive cells. In contrast, the expression of stromal cell-derived factor-1/CXCL12, fractalkine, and CXCR3 is first observed in the comma- or S-shaped body stage. The intensity of this expression becomes stronger in the capillary loop stage, and expression is mainly observed in the mesangial stalk and endothelial cells of the glomeruli. These proteins may play modulatory roles in kidney development. Because genes that are expressed during ontogeny often play a role in tissue regeneration, these embryonal chemokine/chemokine receptor patterns may be important in renal injury and repair.
212Bismuth Linked to an Antipancreatic Carcinoma Antibody: Model for Alpha-Particle-Emitter Radioimmunotherapy
Authors: S. H. Kurtzman, A. Russo, J. B. Mitchell, W. DeGraff, W. F. Sindelar, M. W. Brechbiel, O. A. Gansow, A. M. Friedman, J. J. Hines, J. Gamson, R. W. Atcher
Journal: JNCI Journal of the National Cancer Institute (1988)

For comparison of cytotoxicity from alpha-particle irradiation with that from conventional x-irradiation, 212Bi, an alpha-emitting ra-dionuclide, was attached to a monoclonal antibody that recognizes a cell surface antigen on human pancreatic carcinoma cells. For a given level of survival, the 212Bi-antibody
Development of Tachyphylaxis to Aspartyl <sup>1</sup> and Not to Asparginyl <sup>1</sup> Angiotensin II in the Rat
Authors: MOHINDER P. SAMBHI, JACK D. BARRETT
Journal: Circulation Research (1967)

Pressor responses to single increasing doses (0.001 to 10 µg) and constant infusions (0.01 to 5 mg/kg per hr) of synthetic aspartyl 1 angiotensin II (Asp 1 ) and asparginyl 1 angiotensin II (Aspg 1 , Hypertensin, CIBA) were measured in normal and nephrectomized rats. Mean blood pressure was recorded directly using strain gauges. Angiotensin tachyphylaxis (decline of maximal response to increasing doses, or return of blood pressure to control levels on constant infusion) was consistently seen with greater than minimal doses of Asp 1 while the phenomenon was not observed with Aspg 1 at any dose level. The results indicate that in the rat the two octapeptide analogues of angiotensin are not identical in biologic activity as has been previously held, and that the N-terminal amino acid plays an important part in determining the pressor responsiveness especially to higher doses of angiotensin peptides. The pattern of response and development of tachyphylaxis to Asp 1 closely resembles that of well known tachyphylaxis to renin. These results lend further support to our earlier findings that Asp 1 represents the natural form of angiotensin released in vivo. Renin tachyphylaxis may in its entirety be explained to depend upon the actions of Asp 1 released by renin in plasma. Tachyphylaxis to endogenous angiotensin in pathologic as well as certain physiologic conditions may be expected to occur at lower dose levels than is indicated by the available experimental work with Aspg 1 .
Prostaglandin production by rheumatoid synovial cells: stimulation by a factor from human mononuclear Cells.
Authors: J M Dayer, D R Robinson, S M Krane
Journal: The Journal of Experimental Medicine (1977)

Human peripheral blood mononuclear cells (lymphocyte-monocyte) in culture release a solube factor which can stimulate, up to 200-fold, production of prostaglandin E2 by isolated, adherent, rheumatoid synovial cells. Production of the factor by the mononuclear cells is enhanced by phytohemagglutinin. This factor is similar in apparent mol vt (10,000-20,000) to that which also stimulates collagenase production by the same cells.
The use of β-adrenergic drugs improves hepatic oxygen metabolism in cirrhotic patients undergoing liver resection
Authors: Pilar Taurà, Josep Fuster, Jordi Mercadal, Graciela Martinez-Palli, Constantino Fondevila, Annabel Blasi, Jaume Balust, Juan-Carlos Garcia-Valdecasas
Journal: Journal of Hepatology (2009)
Antibody-Dependent Natural Killer Cell–Mediated Cytotoxicity Engendered by a Kinase-Inactive Human HER2 Adenovirus-Based Vaccination Mediates Resistance to Breast Tumors
Authors: Chiara Triulzi, Simona Vertuani, Claudia Curcio, Agnese Antognoli, Josef Seibt, Göran Akusjärvi, Wei-Zen Wei, Federica Cavallo, Rolf Kiessling
Journal: Cancer Research (2010)

Abstract Cancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report contributions by antibody responses and natural killer (NK) cells in tumor protection in this model. One i.p. vaccination protected WT mice from the HER2-expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were protected fully and long term after preventive vaccination. Tumor growth in mice that eventually developed neoplastic lesions was delayed. Protection in WT and HER2 transgenic mice was associated with high or low levels of IgG2a antibodies, respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice. Depleting CD4+ or CD8+ cells in vaccinated WT mice had limited effects, suggesting that protection was largely independent of CD4+ or CD8+ T cells. In contrast, antibody-mediated tumor rejection seemed to contribute significantly based on a loss of protection in mice deficient for Fc-γ RI/III or B cells. Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells was indicated by evidence that vaccine protection could be abolished by in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells in vitro. Our findings define a critical requirement for NK cells in vaccine-induced protection against HER2-expressing tumors. Cancer Res; 70(19); 7431–41. ©2010 AACR.
Physical performance changes after unsupervised training during the autumn/spring semester break in competitive tennis players
Authors: Mark S Kovacs, Robert Pritchett, P Jason Wickwire, J Matthew Green, Phillip Bishop
Journal: British Journal of Sports Medicine (2007)

Background: All competitive tennis players take time away from coaches throughout the year; however, little information is available as to the short-term physiological effect of these breaks. Objective: The purpose of this investigation was to evaluate the impact of a 5 week off-campus structured, yet unsupervised, break from regular training in top collegiate tennis players. Methods: A nationally ranked collegiate NCAA Division I male tennis team (n = 8) performed a test battery in December and again in January after a 5 week period of recommended, yet unsupervised, training. The tests performed were 5, 10 and 20 m sprints, spider agility test, medicine ball power throws, standing long jump, Wingate anaerobic power test, VO 2max , push-up and sit-up test, grip strength and range of motion (ROM) measures (goniometer) of the shoulder, hip, hamstring and quadriceps. Results: Paired t tests (p&lt;0.05) showed significant decreases in mean (SEM) Wingate power measurements in Watts/kg (pre: 8.35 (0.19) w/kg ; post: 7.80 (0.24) w/kg ), minimum Wingate power (pre: 5.89 (0.27) w/kg; post: 5.10 (0.38) w/kg) and VO 2max values (pre: 53.90 (1.11) ml/kg/min; post: 47.86 (1.54) ml/kg/min). A significant increase was seen in the athlete’s fatigue index (pre: 44.26 (2.85)%; post: 51.41 (3.53)%), fastest 5 m (pre: 1.07 (0.03) s; post: 1.12 (0.02) s), 10 m (pre: 1.79 (0.03) s; post: 1.84 (0.04) s) and 20 m (pre: 3.07 (0.05) s; post: 3.13 (0.05) s) sprint times. No significant differences were seen for the other variables tested. Conclusions: These results suggest that a 5 week interruption of normal training can result in significant reductions in speed, power and aerobic capacity in competitive tennis players, likely owing to poor compliance with the prescribed training regimen. Therefore, coaches and trainers might benefit from techniques (eg, pre- and post-testing) requiring athletes’ to have accountability for unsupervised workouts.
Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)
Authors: S. Ramalingam, J. Crawford, A. Chang, C. Manegold, R. Perez-Soler, J.-Y. Douillard, N. Thatcher, F. Barlesi, T. Owonikoko, Y. Wang, P. Pultar, J. Zhu, R. Malik, G. Giaccone, S. Della-Fiorentina, S. Begbie, R. Jennens, J. Dass, K. Pittman, N. Ivanova, T. Koynova, P. Petrov, A. Tomova, V. Tzekova, F. Couture, V. Hirsh, R. Burkes, R. Sangha, M. Ambrus, T. Janaskova, J. Musil, J. Novotny, P. Zatloukal, J. Jakesova, K. Klenha, J. Roubec, J. Vanasek, J. Fayette, F. Barlesi, J. Bennouna-Louridi, C. Chouaid, J. Mazières, H. Vallerand, G. Robinet, P.-J. Souquet, D. Spaeth, R. Schott, H. Lena, Y. Martinet, C. El Kouri, N. Baize, A. Scherpereel, O. Molinier, F. Fuchs, K.M. Josten, C. Manegold, N. Marschner, F. Schneller, T. Overbeck, M. Thomas, J. von Pawel, M. Reck, W. Schuette, V. Hagen, C.-P. Schneider, V. Georgoulias, I. Varthalitis, K. Zarogoulidis, K. Syrigos, C. Papandreou, C. Bocskei, E. Csanky, E. Juhasz, G. Losonczy, Z. Mark, I. Molnar, Z. Papai-Szekely, S. Tehenes, I. Vinkler, S. Almel, A. Bakshi, S. Bondarde, A. Maru, A. Pathak, R.M. Pedapenki, K. Prasad, S.V.S.S. Prasad, N. Kilara, D. Gorijavolu, C.D. Deshmukh, S. John, L.M. Sharma, D. Amoroso, E. Bajetta, P. Bidoli, A. Bonetti, F. De Marinis, M. Maio, R. Passalacqua, S. Cascinu, A. Bearz, M. Bitina, A. Brize, G. Purkalne, M. Skrodele, A.A. Baba, K. Ratnavelu, M.H. Saw, M.C. Samson-Fernando, G.E. Ladrera, J. Jassem, P. Koralewski, P. Serwatowski, M. Krzakowski, C. Cebotaru, D. Filip, D.E. Ganea-Motan, C.H. Ianuli, I.G. Manolescu, A. Udrea, O. Burdaeva, M. Byakhov, A. Filippov, S. Lazarev, I. Mosin, S. Orlov, D. Udovitsa, A. Khorinko, S. Protsenko, A. Chang, H.L. Lim, Y.O. Tan, E.H. Tan, R. Bastus Piulats, J. Garcia-Foncillas, J. Valdivia, J. de Castro, M. Domine Gomez, S.W. Kim, J.-S. Lee, H.K. Kim, J.S. Lee, S.W. Shin, D.-W. Kim, Y.-C. Kim, K.C. Park, C.-S. Chang, G.-C. Chang, Y.-G. Goan, W.-C. Su, C.-M. Tsai, H.-P. Kuo, M. Benekli, G. Demir, E. Gokmen, A. Sevinc, J. Crawford, G. Giaccone, M. Haigentz, T. Owonikoko, M. Agarwal, S. Pandit, R. Araujo, N. Vrindavanam, P. Bonomi, A. Berg, J. Wade, R. Bloom, B. Amin, R. Camidge, D. Hill, M. Rarick, P. Flynn, L. Klein, K. Lo Russo, M. Neubauer, P. Richards, R. Ruxer, M. Savin, D. Weckstein, R. Rosenberg, T. Whittaker, D. Richards, W. Berry, C. Ottensmeier, A. Dangoor, N. Steele, Y. Summers, E. Rankin, K. Rowley, S. Giridharan, H. Kristeleit, C. Humber, P. Taylor
Journal: Annals of Oncology (2013)
Performance Measurement in Search of a Path
Authors: Rodney A. Hayward
Journal: New England Journal of Medicine (2007)

In this issue of the Journal, Landon and colleagues report on a Herculean undertaking — a study of quality-improvement interventions conducted at 44 community health centers.1 This study showed a modest improvement in some process measures and no improvement in intermediate or end-stage outcomes — results that are similar to those of most previous large-scale quality-improvement initiatives. As the authors correctly note, improved processes may not be accompanied by discernible improvements in outcomes for several reasons. A particularly important problem is that the majority of Health Plan Employer Data and Information Set–style performance measures used to guide most large-scale quality-improvement . . .
Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT)
Authors: Alex J. Mackay, Gavin C. Donaldson, Anant R.C. Patel, Richa Singh, Beverly Kowlessar, Jadwiga A. Wedzicha
Journal: European Respiratory Journal (2013)

Uncertainty exists over the ability of the exacerbations of chronic pulmonary disease tool (EXACT) patient-reported outcome diary to quantify exacerbation severity and frequency. To clarify this, we investigated the ability of the EXACT to assess severity of exacerbations and examined the relationship between exacerbations diagnosed using London chronic obstructive pulmonary disease (COPD) cohort diary cards, physician review and symptom-defined events using the EXACT. 58 patients enrolled in the London Chronic Obstructive Pulmonary Disease (COPD) cohort prospectively completed the EXACT during 128 cohort diary card-defined exacerbations between January 2010 and April 2012. Mean ± sd EXACT scores increased from 42.6 ± 8.6 at baseline to 48.0 ± 8.6 at exacerbation onset (p<0.001), and rose further to a maximum score of 54.1 ± 8.9. Maximum EXACT scores were significantly higher in treated than untreated events. Time taken for EXACT scores to return to baseline was significantly related to symptom recovery time as judged by London COPD cohort diary cards, and to peak expiratory flow rate recovery. ∼50% of both diary card-defined and healthcare utilisation exacerbations crossed the EXACT event threshold. However, only 27.9% of diary card-defined and 34.6% of healthcare utilisation exacerbations fully met the criteria for an EXACT event. Patients exhibited smaller rises in the EXACT score at exacerbation as baseline disease severity increased. The EXACT is an effective method of evaluating chronic obstructive pulmonary disease exacerbation severity. However, concerns remain about the ability of the EXACT to accurately detect exacerbations.
A Bayesian network meta-analysis comparing concurrent chemoradiotherapy followed by adjuvant chemotherapy, concurrent chemoradiotherapy alone and radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma
Authors: Y.P. Chen, Z.X. Wang, L. Chen, X. Liu, L.L. Tang, Y.P. Mao, W.F. Li, A.H. Lin, Y. Sun, J. Ma
Journal: Annals of Oncology (2014)
Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study
Authors: Min-Juei Tsai, Shuo-Ming Ou, Chia-Jen Shih, Pei-wen Chao, Lan-Fu Wang, Yu-Ning Shih, Szu-Yuan Li, Shu-Chen Kuo, Yen-Tao Hsu, Yung-Tai Chen
Journal: Intensive Care Medicine (2015)
<i>In vivo</i> Radioprotection by the Fullerene Nanoparticle DF-1 as Assessed in a Zebrafish Model
Authors: Borbala Daroczi, Gabor Kari, Mary Frances McAleer, Jeffrey C. Wolf, Ulrich Rodeck, Adam P. Dicker
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have previously shown that zebrafish (Danio rerio) embryos can be used as an in vivo model to validate modifiers of the radiation response. Here, we evaluated the radioprotective effect of the nanoparticle DF-1, a fullerene with antioxidant properties, in zebrafish embryos. Experimental Design: Zebrafish embryos were exposed to different doses of ionizing radiation ranging from 20 to 80 Gy in the presence and absence of DF-1. Toxicity and radioprotective effects were assessed by monitoring overall survival and morphology as well as organ functions by employing assays to measure kidney excretory function and development of sensory nerve cells (neuromasts). Antioxidant properties of DF-1 were assessed in whole fish. Results: DF-1 had no apparent adverse effects on normal zebrafish morphology or viability throughout the concentration range tested (1-1,000 μmol/L). Ionizing radiation (10-40 Gy) caused time-dependent and dose-dependent perturbations of normal zebrafish morphology and physiology, notably defective midline development resulting in dorsal curvature of the body axis (“curly-up”), neurotoxicity, impaired excretory function, and decreased survival of the exposed embryos. DF-1 (100 μmol/L) markedly attenuated overall and organ-specific radiation-induced toxicity when given within 3 hours before or up to 15 minutes after radiation exposure. By contrast, DF-1 afforded no protection when given 30 minutes after ionizing radiation. The degree of radioprotection provided by DF-1 was comparable with that provided by the Food and Drug Administration–approved radioprotector amifostine (4 mmol/L). Protection against radiation-associated toxicity using DF-1 in zebrafish embryos was associated with marked reduction of radiation-induced reactive oxygen species. Conclusion: The fullerene DF-1 protects zebrafish embryos against deleterious effects of ionizing radiation due, in part, to its antioxidant properties.
Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes
Authors: Eva Corpeleijn, Edith J.M. Feskens, Eugène H.J.M. Jansen, Marco Mensink, Wim H.M. Saris, Ellen E. Blaak
Journal: Diabetes Care (2007)

OBJECTIVE—We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin, adiponectin, and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance. RESEARCH DESIGN AND METHODS—In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht, 147 men and women with impaired glucose tolerance (IGT) were randomized to either a combined diet-and-exercise intervention or a control program. At baseline and after 1 year, an oral glucose tolerance test, an exercise test, and anthropometric measurements were performed. After 1 year, complete data of 103 subjects (50 intervention and 53 control subjects) were obtained. RESULTS—Lifestyle intervention reduced plasma leptin concentrations (−14.2%) in IGT subjects but did not alter plasma adiponectin (−0.3%) or resistin (−6.5%) concentrations despite marked improvements in glucose tolerance and insulin resistance. CONCLUSIONS—Changes in leptin concentration were related to improvements in insulin sensitivity independent of changes in body composition.