tbuckley/cabot-search huggingface dataset:
Understanding/acceptance and adaptation: Is the non-normative thinking mode adaptive?
Authors: Jerwen Jou
Journal: Behavioral and Brain Sciences (2000)

The finding of a correlation between normative responses to judgment and reasoning questions and cognitive capacity measures (SAT score) suggests that the cause of the non-normative responses is computational in nature. This actually is consistent with the rational competence view. The implications of this finding for the adaptation view of cognition are discussed.
Hospitals still fail to provide accurate records of the patients they treat
Authors: N. Hawkes
Journal: BMJ (2014)

Hospitals continue to make errors in clinical coding, which can cost them money and create further errors in monitoring systems that depend on accurate data. While most hospitals largely get these data right, one trust of the 50 audited by CHKS/Capita in 2013-14 got almost half of the codes wrong, a new report has shown.1

Failure to code accurately can result in hospitals being paid too little or too much, depending on the errors made. Over the sample as a whole these errors roughly balanced out, so no evidence suggested that codes were being deliberately inflated to boost a hospital’s income. One common error was to fail to code completely for comorbidities, which …
First-in-Human Phase I Study of the Liposomal RNA Interference Therapeutic Atu027 in Patients With Advanced Solid Tumors
Authors: Beate Schultheis, Dirk Strumberg, Ansgar Santel, Christiane Vank, Frank Gebhardt, Oliver Keil, Christian Lange, Klaus Giese, Jörg Kaufmann, Michael Khan, Joachim Drevs
Journal: Journal of Clinical Oncology (2014)

Atu027 is a novel liposomal RNA interference therapeutic that includes a short-interfering RNA (siRNA), which silences expression of protein kinase N3 in the vascular endothelium. Atu027 has previously been shown to inhibit local tumor invasion as well as lymph node and pulmonary metastasis in mouse cancer models. This first-in-human study aimed to assess the safety, tolerability, and pharmacokinetics of Atu027 while evaluating therapeutic effects on both primary tumors and metastatic lesions.Thirty-four patients with advanced solid tumors received 10 escalating doses of Atu027 without premedication, as one single followed by eight intravenous infusions twice per week during a 28-day cycle. Response was monitored by computed tomography/magnetic resonance imaging at baseline, at the end of treatment (EoT), and at final follow-up (EoS), and was assessed according to RECIST.Atu027 was well tolerated up to dose levels of 0.336 mg/kg; most adverse events (AEs) were low-grade toxicities (grade 1 or 2). No maximum tolerated dose was reached. Plasma levels of siRNA strands and lipids were dose proportional, peaking during 4-hour infusion. Disease stabilization was achieved in 41% of patients at EoT (n = 14 of 34 treated patients); eight patients had stable disease at EoS, and some experienced complete or partial regression of metastases. sFLT1 (soluble variant of vascular endothelial growth factor receptor-1) decreased from pretreatment levels in most patients after dose levels 04 to 10.Atu027 was safe in patients with advanced solid tumors, with 41% of patients having stable disease for at least 8 weeks. In view of these results, further clinical trials have been initiated, and sFLT1 will be investigated as a potential biomarker.
Negative Action of Hepatocyte Growth Factor/c-Met System on Angiotensin II Signaling via Ligand-Dependent Epithelial Growth Factor Receptor Degradation Mechanism in Vascular Smooth Muscle Cells
Authors: Fumihiro Sanada, Yoshiaki Taniyama, Kazuma Iekushi, Junya Azuma, Keita Okayama, Hiroshi Kusunoki, Nobutaka Koibuchi, Takefumi Doi, Yoshifusa Aizawa, Ryuichi Morishita
Journal: Circulation Research (2009)

Rationale: Neointimal hyperplasia contributes to atherosclerosis and restenosis after percutaneous coronary intervention. Vascular injury in each of these conditions results in the release of mitogenic growth factors and hormones that contribute to pathological vascular smooth muscle cell growth and inflammation. Hepatocyte growth factor (HGF) is known as an antiinflammatory growth factor, although it is downregulated in injured tissue. However, the precise mechanism how HGF reduces inflammation is unclear. Objective: To elucidate the mechanism how HGF and its receptor c-Met reduces angiotensin II (Ang II)–induced inflammation. Methods and Results: HGF reduced Ang II–induced vascular smooth muscle cell growth and inflammation by controlling translocation of SHIP2 (Src homology domain 2–containing inositol 5′-phosphatase 2), which led to Ang II–dependent degradation of epithelial growth factor receptor. Moreover, the present study also revealed a preventive effect of HGF on atherosclerotic change in an Ang II infusion and cuff HGF transgenic mouse model. Conclusions: These data suggest that the HGF/c-Met system might regulate extrinsic factor signaling that maintains the homeostasis of organs.
THE TREATMENT OF ERYTHRASMA IN A HOSPITAL FOR THE MENTALLY SUBNORMAL
Authors: R. H. SEVILLE, DOROTHY A. SOMERVILLE
Journal: British Journal of Dermatology (1970)

SUMMARY.— Erythrasma of axillae, groins and feet was treated in a double blind controlled trial. The following preparations were used and are given in order of effectiveness; Whitfield's ointment, framycetin ointment, erythromycin, oxytetracycline and Tinaderm. A placebo was ineffective.
Preliminary Results of a Randomized Study on Therapeutic Gain by Concurrent Chemotherapy for Regionally-Advanced Nasopharyngeal Carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group
Authors: Anne W.M. Lee, W.H. Lau, Stewart Y. Tung, Daniel T.T. Chua, Rick Chappell, L. Xu, Lillian Siu, W.M. Sze, T.W. Leung, Jonathan S.T. Sham, Roger K.C. Ngan, Stephen C.K. Law, T.K. Yau, Joseph S.K. Au, Brian O'Sullivan, Ellie S.Y. Pang, S.K. O, Gordon K.H. Au, Joseph T. Lau
Journal: Journal of Clinical Oncology (2005)

This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease.Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127.From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024).Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.
Rosette-forming ability of thymus-derived lymphocytes in humoral and cell-mediated immunity. II. Helper cell activity.
Authors: B E Elliott, J S Haskill
Journal: The Journal of Experimental Medicine (1975)

The technique of velocity sedimentation at unit gravity was used to determine the size and rosette-forming ability of helper cells in nonimmune and immune C57BL/6 mice. Helper T cells were assayed by the ability to cooperate with bone barrow (B) cells in the antibody response to sheep erythrocytes (SRBC) in vivo. 19S helper cells in nonimmune animals were nonrosette-forming small lymphocytes; after immunization with SRBC in complete Freund's adjuvant, 19S helper cells were nonrosette-forming medium lymphocytes. 7S helper cells in immune animals were small lymphocytes which did not form rosettes. No SRBC binding by helper cells was observed under the conditions of rosette formation used.
Self correction of refractive error among young people in rural China: results of cross sectional investigation
Authors: M. Zhang, R. Zhang, M. He, W. Liang, X. Li, L. She, Y. Yang, G. MacKenzie, J. D. Silver, L. Ellwein, B. Moore, N. Congdon
Journal: BMJ (2011)

<b>Objective</b> To compare outcomes between adjustable spectacles and conventional methods for refraction in young people. <b>Design</b> Cross sectional study. <b>Setting</b> Rural southern China. <b>Participants</b> 648 young people aged 12-18 (mean 14.9 (SD 0.98)), with uncorrected visual acuity ≤6/12 in either eye. <b>Interventions</b> All participants underwent self refraction without cycloplegia (paralysis of near focusing ability with topical eye drops), automated refraction without cycloplegia, and subjective refraction by an ophthalmologist with cycloplegia. <b>Main outcome measures</b> Uncorrected and corrected vision, improvement of vision (lines on a chart), and refractive error. <b>Results</b> Among the participants, 59% (384) were girls, 44% (288) wore spectacles, and 61% (393/648) had 2.00 dioptres or more of myopia in the right eye. All completed self refraction. The proportion with visual acuity ≥6/7.5 in the better eye was 5.2% (95% confidence interval 3.6% to 6.9%) for uncorrected vision, 30.2% (25.7% to 34.8%) for currently worn spectacles, 96.9% (95.5% to 98.3%) for self refraction, 98.4% (97.4% to 99.5%) for automated refraction, and 99.1% (98.3% to 99.9%) for subjective refraction (P=0.033 for self refraction <i>v</i> automated refraction, P=0.001 for self refraction <i>v</i> subjective refraction). Improvements over uncorrected vision in the better eye with self refraction and subjective refraction were within one line on the eye chart in 98% of participants. In logistic regression models, failure to achieve maximum recorded visual acuity of 6/7.5 in right eyes with self refraction was associated with greater absolute value of myopia/hyperopia (P&lt;0.001), greater astigmatism (P=0.001), and not having previously worn spectacles (P=0.002), but not age or sex. Significant inaccuracies in power (≥1.00 dioptre) were less common in right eyes with self refraction than with automated refraction (5% v 11%, P&lt;0.001). <b>Conclusions</b> Though visual acuity was slightly worse with self refraction than automated or subjective refraction, acuity was excellent in nearly all these young people with inadequately corrected refractive error at baseline. Inaccurate power was less common with self refraction than automated refraction. Self refraction could decrease the requirement for scarce trained personnel, expensive devices, and cycloplegia in children's vision programmes in rural China.
Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies
Authors: J.M. Genkinger, M. Wang, R. Li, D. Albanes, K.E. Anderson, L. Bernstein, P.A. van den Brandt, D.R. English, J.L. Freudenheim, C.S. Fuchs, S.M. Gapstur, G.G. Giles, R.A. Goldbohm, N. Håkansson, P.L. Horn-Ross, A. Koushik, J.R. Marshall, M.L. McCullough, A.B. Miller, K. Robien, T.E. Rohan, C. Schairer, D.T. Silverman, R.Z. Stolzenberg-Solomon, J. Virtamo, W.C. Willett, A. Wolk, R.G. Ziegler, S.A. Smith-Warner
Journal: Annals of Oncology (2014)
In a novel form of IFN-γ receptor 1 deficiency, cell surface receptors fail to bind IFN-γ
Authors: Emmanuelle Jouanguy, Stéphanie Dupuis, Annaïck Pallier, Rainer Döffinger, Marie-Claude Fondanèche, Claire Fieschi, Salma Lamhamedi-Cherradi, Frédéric Altare, Jean-François Emile, Patrick Lutz, Pierre Bordigoni, Haluk Cokugras, Necla Akcakaya, Judith Landman-Parker, Jean Donnadieu, Yildiz Camcioglu, Jean-Laurent Casanova
Journal: Journal of Clinical Investigation (2000)

Complete IFN-γ receptor ligand-binding chain (IFNγR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNγR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNγR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of 125I–IFN-γ to cells was observed in any patient, however, and the cells failed to respond to IFN-γ. The mutations therefore cause complete IFNγR1 deficiency by disrupting the IFN-γ–binding site without affecting surface expression. The detection of surface IFNγR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNγR1 deficiency.
Demonstration of a Genetic Therapeutic Index for Tumors Expressing Oncogenic <i>BRAF</i> by the Kinase Inhibitor SB-590885
Authors: Alastair J. King, Denis R. Patrick, Roberta S. Batorsky, Maureen L. Ho, Hieu T. Do, Shu Yun Zhang, Rakesh Kumar, David W. Rusnak, Andrew K. Takle, David M. Wilson, Erin Hugger, Lifu Wang, Florian Karreth, Julie C. Lougheed, Jae Lee, David Chau, Thomas J. Stout, Earl W. May, Cynthia M. Rominger, Michael D. Schaber, Lusong Luo, Ami S. Lakdawala, Jerry L. Adams, Rooja G. Contractor, Keiran S.M. Smalley, Meenhard Herlyn, Michael M. Morrissey, David A. Tuveson, Pearl S. Huang
Journal: Cancer Research (2006)

Oncogenic BRAF alleles are both necessary and sufficient for cellular transformation, suggesting that chemical inhibition of the activated mutant protein kinase may reverse the tumor phenotype. Here, we report the characterization of SB-590885, a novel triarylimidazole that selectively inhibits Raf kinases with more potency towards B-Raf than c-Raf. Crystallographic analysis revealed that SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration, which is distinct from the previously reported mechanism of action of the multi-kinase inhibitor, BAY43-9006. Malignant cells expressing oncogenic B-Raf show selective inhibition of mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity when exposed to SB-590885, whereas other cancer cell lines and normal cells display variable sensitivities or resistance to similar treatment. These studies support the validation of oncogenic B-Raf as a target for cancer therapy and provide the first evidence of a correlation between the expression of oncogenic BRAF alleles and a positive response to a selective B-Raf inhibitor.
Explaining Marginal Benefits to Patients, When “Marginal” Means Additional but Not Necessarily Small
Authors: Thomas J. Smith, Bruce E. Hillner
Journal: Clinical Cancer Research (2010)

Abstract Patients and their families want us to be realistic, honest, and caring about their prognosis and their options, even when the news is bad. Most oncologists will tell a patient if he is not curable, but not give specific survival information unless prompted. As an example, chemotherapy for pancreas cancer improves survival and does not worsen quality of life, but the impact on lifespan is small. Patients with advanced pancreas cancer have options that increase their average survival by about 16/100 at 1 year, and by about 9 weeks compared with best supportive care, but almost all patients are dead by 24 months. As an example of “marginal benefit” (“marginal” is defined here as more than that offered by the alternative care, not necessarily small or worthless), erlotinib added to gemcitabine compared with gemcitabine alone improves survival by six additional people at 1 year, and an average of 2 weeks, with no survival tail. In addition, the additional drug cost alone can be more than $12,000 a month. We use this clinical practice as a way to describe marginal benefit to patients. Telling patients that they have incurable disease and that treatment is ineffective is hard. Partly as a result, only about a third of cancer patients are told they are going to die, and those who are not told live no longer but have worse medical outcomes, such as dying on a ventilator and less time with hospice. These difficult conversations can be done if the oncologist has the right medical information, the right script, and some decision aids. Clin Cancer Res; 16(24); 5981–6. ©2010 AACR.
PSYCHOSIS AND ALLERGY: EXPERIMENTAL APPROACH
Authors: DANIEL X. FREEDMAN, F. C. REDLICH, WALTER W. IGERSHEIMER
Journal: American Journal of Psychiatry (1956)

1. Twenty-two schizophrenic patients and 22 preclinical medical students were skin tested with a battery of allergens, histamine and cantharides, to test experimentally the hypothesis that psychosis involves diminished ability to react allergically. 2. The patient group showed no diminished ability to react allergically when compared with controls, but did have consistently smaller wheal response to histamine. 3. It is suggested that while neither hypoergic nor hyporeactive in the skin, the schizophrenic patient may differ from the normal with respect to certain links in the allergic process, and may so differ without of necessity clinically manifesting this. 4. Alteration in central nervous system function in schizophrenia—possibly diencephalic or reticular—may account for the differences in histamine response and the reported differences in autonomic responsivity, in ability contemporaneously to develop sensitization and to respond to antigen with high titre of antibodies.
Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models
Authors: Junjie Li, Marlein Miranda Cona, Feng Chen, Yuanbo Feng, Lin Zhou, Jie Yu, Johan Nuyts, Peter de Witte, Jian Zhang, Uwe Himmelreich, Alfons Verbruggen, Yicheng Ni
Journal: Theranostics (2012)

Objectives: The present animal experiments were conducted to evaluate radioiodinated Hypericin (Hyp) for its regional distribution as well as theranostic potentials.Materials and Methods: Rat models of reperfused liver infarction (RLI) and hepatic rhabdomyosarcoma (R1) were surgically induced.R1 models received Combretastatin A4 phosphate (CA4P) intravenously at 10 mg/kg 24 h prior to radioiodinated Hyp.Three groups of 6 rats each containing 3 RLI and 3 R1 models received iv injections of 123 I-Hyp at 37, 74, and 185 MBq/kg respectively and followed by 0.1 ml of 1% Evans blue solution were sacrificed at 4, 24 and 48 hour post injection immediately after in vivo examination of MRI and planar gamma scintigraphy.Besides, two groups of 6 R1 models that received either 300 MBq/kg of 131 I-Hyp or vehicle intravenously were examined using MRI to compare tumor growth for 12 days.Autoradiography, gamma counting, and histopathology were performed for postmortem verifications and quantification.Results: Necrosis as seen in vivo on contrast-enhanced MRI corresponded well with the hot spots on planar scintigraphy.Autoradiography and gamma counting revealed intense accumulation of 123 I-Hyp in necrotic liver (3.94 ± 1.60, 5.38 ± 1.04, and 6.03 ± 2.09 %ID/g ± SD) and necrotic tumor (4.27 ± 0.76, 5.57 ± 0.76, and 5.68 ± 1.33 %ID/g ± SD) relative to normal liver (1.76 ± 0.54, 0.41 ± 0.18, and 0.16 ± 0.07 %ID/g ± SD), with a high necrosis-to-liver ratio of 2.3, 14.0, and 37.0 at 4, 24 and 48 h respectively.Tumor volumes in R1 models that received 131 I-Hyp and vehicle changed from 0.45 ± 0.09, and 0.47 ± 0.12 cm 3 (p > 0.05) on day 0 to1.32 ± 0.76 and 3.63 ± 0.72 cm 3 (p < 0.001) on day 12, with the corresponding necrosis ratios from 73 ± 12 %, and 76 ± 17 % to 47 ± 18% and 17 ± 13 % (p < 0.01), and with the tumor DT of 7.3 ± 1.0 and 4.2 ± 0.7 days, respectively.Conclusions: Radioiodinated Hyp as a necrosis avid tracer appears promising for non-invasive imaging diagnosis of necrosis-related pathologies.Its prominent targetability to necrosis allows targeted radiotherapy for malignancies on top of a prior necrosis-inducing treatment.
Eccentric overload training in patients with chronic Achilles tendinopathy: a systematic review
Authors: J J Kingma, R de Knikker, H M Wittink, T Takken
Journal: British Journal of Sports Medicine (2006)

Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the literature. Methods: Electronic databases were searched for randomised clinical trials concerning eccentric overload training in patients with chronic Achilles tendinopathy. The Delphi list was used to assess the methodological quality of the studies. Results: Nine clinical trials were included. Only one study had sufficient methodological quality. The included trials showed an improvement in pain after eccentric overload training. Because of the methodological shortcomings of the trials, no definite conclusion can be drawn concerning the effects of eccentric overload training in patients with chronic Achilles tendinopathy. Conclusion: The effects of eccentric exercise training in patients with chronic Achilles tendinopathy on pain are promising; however, the magnitude of the effects cannot be determined. Large, methodologically sound studies from multiple sites in which functional outcome measures are included are warranted.
A Genetic Platform to Model Sarcomagenesis from Primary Adult Mesenchymal Stem Cells
Authors: Jlenia Guarnerio, Luisa Riccardi, Riccardo Taulli, Takahiro Maeda, Guocan Wang, Robin M. Hobbs, Min Sup Song, Paolo Sportoletti, Rosa Bernardi, Roderick T. Bronson, Mireia Castillo-Martin, Carlos Cordon-Cardo, Andrea Lunardi, Pier Paolo Pandolfi
Journal: Cancer Discovery (2015)

The regulatory factors governing adult mesenchymal stem cell (MSC) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal forms of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here, we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSC transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF-DLK1-SOX9 pathway in the pathogenesis of undifferentiated sarcoma, with important therapeutic implications.The paucity of therapeutic options for the treatment of sarcoma calls for a rapid and effective preclinical assessment of new therapeutic modalities. We have here developed a new platform to deconstruct the molecular genetics underlying the pathogenesis of sarcoma and to evaluate in vivo the efficacy of novel targeted therapies.