tbuckley/cabot-search huggingface dataset:
Synchronous Alterations of Wnt and Epidermal Growth Factor Receptor Signaling Pathways through Aberrant Methylation and Mutation in Non–Small Cell Lung Cancer
Authors: Makoto Suzuki, Hisayuki Shigematsu, Takahiro Nakajima, Rieko Kubo, Shinichiro Motohashi, Yasuo Sekine, Kiyoshi Shibuya, Toshihiko Iizasa, Kenzo Hiroshima, Yukio Nakatani, Adi F. Gazdar, Takehiko Fujisawa
Journal: Clinical Cancer Research (2007)

The Wnt and epidermal growth factor receptor (EGFR) signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. Although the details of each cascade are understood, very little is known about their collective effects in non-small cell lung cancer (NSCLC).A total of 238 NSCLC samples were examined for methylation of Wnt antagonists [secreted frizzled-related protein (sFRP)-1, sFRP-2, sFRP-5, Wnt inhibitory factor-1, and Dickkopf-3] and for EGFR and KRAS mutations. Protein expression levels of beta-catenin were assayed in 91 of the 238 NSCLCs.We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, nonsmokers, and adenocarcinoma cases; (c) Dickkopf-3 methylation is significantly associated with a poor prognosis in adenocarcinomas; (d) there is a positive correlation between activated EGFR mutation and nuclear accumulation of beta-catenin; (e) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (f) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes.These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways and help foster development of chemotherapeutic treatments in NSCLCs.
Initial Management of the Severely Injured Patient
Authors: G. Tom Shires
Journal: JAMA (1970)

Immediate categorization and an organized plan of management serve to expedite and improve medical care of the severely injured patient. While consultation is obtained from all necessary specialty services, the responsibility should rest with one physician who is able to evaluate the patient's overall problem. With this approach in mind, the following is a description of an approach which has proved practical and effective. <h3>Priority by Injury</h3> Patients may be placed in one of three categories, according to the severity of the injury.<sup>1</sup>The first category includes injuries which interfere with vital physiologic function and constitute an immediate threat to life, such as a gunshot wound, or an obstructed airway. The primary treatment is to establish an airway and control the bleeding. This type of patient may require surgery within five to ten minutes following arrival, especially if there is massive internal bleeding. The operating room is alerted to
STUDIES ON X-RAY EFFECTS
Authors: James B. Murphy, Raymond G. Hussey, Waro Nakahara, Ernest Sturm
Journal: The Journal of Experimental Medicine (1921)

Small areas of the skin in the groin of mice were subjected to an erythema dose of x-rays and a week later a cancer graft was inoculated intracutaneously into the area and at the same time a like graft was inoculated in the same manner in the opposite groin protected from x-rays. The graft in the x-rayed area showed a low percentage of takes, while that in the normal skin gave the usual high percentage When the graft was introduced into the subcutaneous tissues it grew equally as well in the x-rayed area as in the protected area. Histological examination shows the skin layers, a few days after x-ray treatment, to be markedly infiltrated with round cells of the lymphoid type. The reaction did not extend deeper than the skin layers. It is suggested that this local lymphoid reaction induced by the x-rays controls the graft made into the skin, while its absence in deeper tissues accounts for the growth of the grafts more deeply implanted.
BAIT: Organizing genomes and mapping rearrangements in single cells
Authors: Mark Hills, Kieran O’Neill, Ester Falconer, Ryan Brinkman, Peter M Lansdorp
Journal: Genome Medicine (2013)

Strand-seq is a single-cell sequencing technique to finely map sister chromatid exchanges (SCEs) and other rearrangements. To analyze these data, we introduce BAIT, software which assigns templates and identifies and localizes SCEs. We demonstrate BAIT can refine completed reference assemblies, identifying approximately 21 Mb of incorrectly oriented fragments and placing over half (2.6 Mb) of the orphan fragments in mm10/GRCm38. BAIT also stratifies scaffold-stage assemblies, potentially accelerating the assembling and finishing of reference genomes. BAIT is available at http://sourceforge.net/projects/bait/.
Breast Cancer Screening Policies in Developing Countries: A Cost-effectiveness Analysis for India
Authors: Quirine Lamberts Okonkwo, Gerrit Draisma, Arno der Kinderen, Martin L. Brown, Harry J. de Koning
Journal: JNCI Journal of the National Cancer Institute (2008)

India, the largest developing country, has a steadily rising incidence of breast cancer. Estimates and comparisons of the cost-effectiveness of feasible breast cancer screening policies in developing countries and identification of the determinants of cost and efficacy are needed.A Microsimulation Screening Analysis model of breast cancer was calibrated to available data on breast cancer incidence, stage distribution, and mortality in India. The model was used to estimate the costs of screening for breast cancer in India, its effects on mortality, and its cost-effectiveness (ie, costs of screening per life-year gained or life saved). Screening using clinical breast examination (CBE) or mammography among different age groups and at various frequencies was analyzed. Costs were expressed in international dollars (Int.$), the currency used by the World Health Organization, which has the same purchasing power in India as the US dollar has in the United States. To determine which factors influenced cost-effectiveness, sensitivity analyses were performed.The estimated mortality reduction was the greatest for programs targeting women between age 40 and 60 years. Using a 3% discount rate, a single CBE at age 50 had an estimated cost-effectiveness ratio of Int.$793 per life year gained and a breast cancer mortality reduction of 2%. The cost-effectiveness ratio increased to Int.$1135 per life year gained for every-5-year CBE (age 40-60 years) and to Int.$1341 for biennial CBE (age 40-60 years); the corresponding reductions in breast cancer mortality were 8.2% and 16.3%, respectively. CBE performed annually from ages 40 to 60 was predicted to be nearly as efficacious as biennial mammography screening for reducing breast cancer mortality while incurring only half the net costs. The main factors affecting cost-effectiveness were breast cancer incidence, stage distribution, and cost savings on prevented palliative care.The estimated cost-effectiveness of CBE screening for breast cancer in India compares favorably with that of mammography in developed countries. However, in view of competing priorities and economic conditions, the introduction of screening in India represents a greater challenge than it has been in more developed countries.
Adherence to Therapy With Oral Antineoplastic Agents
Authors: A. H. Partridge
Journal: JNCI Journal of the National Cancer Institute (2002)

With the rise in availability and increasing use of oral anticancer agents, concerns about adherence to prescribed regimens will become an increasingly important issue in oncology. Few published studies have focused on adherence to oral antineoplastic therapy, in part because the vast majority of chemotherapy is delivered intravenously in physicians' offices or hospitals. In this article, we review current knowledge of adherence behavior with regard to oral medications in general, including factors associated with adherence and methods for measuring adherence. We also review published studies of adherence to oral antineoplastic agents in adult and pediatric populations and adherence issues in cancer prevention. The available evidence reveals that patient adherence to oral chemotherapy recommendations is variable and not easily predicted. Adherence rates ranging from less than 20% to 100% have been reported, and certain populations, such as adolescents, pose particular challenges. Future efforts should focus on improving measurement and prediction of adherence and on developing interventions to improve adherence for both patients in clinical trials and patients being treated outside of the research setting. Assessment of adherence among individuals with cancer and implementation of interventions in situations of poor adherence should improve clinical outcomes.
Anxiety or Caffeinism: A Diagnostic Dilemma
Authors: JOHN F. GREDEN
Journal: American Journal of Psychiatry (1974)

The author reports that high intake of caffeine (caffeinism) can produce symptoms that are indistinguishable from those of anxiety neurosis, such as nervouness, irritability, tremulousness, occasional muscle twitchings, insomnia, sensory disturbances, tachypnea, palpitations, flushing, arrhythmias, diuresis, and gastrointestinal disturbances. The caffeine withdrawal syndrome and the headache associated with it may also mimic anxiety. Patients with caffeinism will generally be identified only by routine inquiry into their caffeine intake. The psychiatrist should especially suspect caffeinism in patients who do not respond to psychopharmacological agents or who have psychophysiological complaints and recurrent headaches, chronic coffee-drinking patients on inpatient psychiatric services, and hyperkinetic children. Three case reports illustrate the syndrome.
Dual Inhibition of PI3K and mTORC1/2 Signaling by NVP-BEZ235 as a New Therapeutic Strategy for Acute Myeloid Leukemia
Authors: Nicolas Chapuis, Jerome Tamburini, Alexa S. Green, Christine Vignon, Valerie Bardet, Aymeric Neyret, Melanie Pannetier, Lise Willems, Sophie Park, Alexandre Macone, Sauveur-Michel Maira, Norbert Ifrah, François Dreyfus, Olivier Herault, Catherine Lacombe, Patrick Mayeux, Didier Bouscary
Journal: Clinical Cancer Research (2010)

The growth and survival of acute myeloid leukemia (AML) cells are enhanced by the deregulation of signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR). Major efforts have thus been made to develop molecules targeting these activated pathways. The mTOR serine/threonine kinase belongs to two separate complexes: mTORC1 and mTORC2. The mTORC1 pathway is rapamycin sensitive and controls protein translation through the phosphorylation of 4E-BP1 in most models. In AML, however, the translation process is deregulated and rapamycin resistant. Furthermore, the activity of PI3K/Akt and mTOR is closely related, as mTORC2 activates the oncogenic kinase Akt. We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis).The activity of NVP-BEZ235 was tested in primary AML samples (n = 21) and human leukemic cell lines. The different signaling pathways were analyzed by Western blotting. The cap-dependent mRNA translation was studied by 7-methyl-GTP pull-down experiments, polysomal analysis, and [(3)H]leucine incorporation assays. The antileukemic activity of NVP-BEZ235 was tested by analyzing its effects on leukemic progenitor clonogenicity, blast cell proliferation, and survival.The NVP-BEZ235 compound was found to inhibit PI3K and mTORC1 signaling and also mTORC2 activity. Furthermore, NVP-BEZ235 fully inhibits the rapamycin-resistant phosphorylation of 4E-BP1, resulting in a marked inhibition of protein translation in AML cells. Hence, NVP-BEZ235 reduces the proliferation rate and induces an important apoptotic response in AML cells without affecting normal CD34(+) survival.Our results clearly show the antileukemic efficiency of the NVP-BEZ235 compound, which therefore represents a promising option for future AML therapies.
Induction of Robust Type-I CD8+ T-cell Responses in WHO Grade 2 Low-Grade Glioma Patients Receiving Peptide-Based Vaccines in Combination with Poly-ICLC
Authors: Hideho Okada, Lisa H. Butterfield, Ronald L. Hamilton, Aki Hoji, Masashi Sakaki, Brian J. Ahn, Gary Kohanbash, Jan Drappatz, Johnathan Engh, Nduka Amankulor, Mark O. Lively, Michael D. Chan, Andres M. Salazar, Edward G. Shaw, Douglas M. Potter, Frank S. Lieberman
Journal: Clinical Cancer Research (2014)

WHO grade 2 low-grade gliomas (LGG) with high risk factors for recurrence are mostly lethal despite current treatments. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in HLA-A2(+) adults with high-risk LGGs in the following three cohorts: (i) patients without prior progression, chemotherapy, or radiotherapy (RT); (ii) patients without prior progression or chemotherapy but with prior RT; and (iii) recurrent patients.GAAs were IL13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for eight courses with intramuscular injections of poly-ICLC, followed by q12 week booster vaccines.Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with grade 3 fever, fatigue, and mood disturbance (cohort 1). ELISPOT assays demonstrated robust IFNγ responses against at least three of the four GAA epitopes in 10 and 4 cases of cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFNγ responses than cohort 3 patients. Median progression-free survival (PFS) periods since the first vaccine are 17 months in cohort 1 (range, 10-47+) and 12 months in cohort 3 (range, 3-41+). The only patient with large astrocytoma in cohort 2 has been progression-free for more than 67 months since diagnosis.The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade 2 glioma patients. These results warrant further evaluations of this approach. Clin Cancer Res; 21(2); 286-94. ©2014 AACR.
I-test: a new clinical education feature for the British Journal of Sports Medicine
Authors: Bruce B Forster
Journal: British Journal of Sports Medicine (2009)

As part of the British Journal of Sports Medicine ’s ( BJSM ) emphasis on continuing clinical education, we launch the imaging education feature—“I-test” (imaging test). Each I-test will consist of a short history, key physical examination findings and imaging findings that are needed to arrive at a diagnosis. Images will reflect the breadth of clinical practice and include plain radiographs, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). We will emphasise clinical utility—common conditions in which selection of the correct …
Benign endobronchial tumours treated by neodymium-YAG laser
Authors: P Eppinga, K T van der Laan, J J Overbeek, A F Meinesz, P E Postmus
Journal: European Respiratory Journal (1988)

We present two patients with benign endobronchial tumours: polypi and a chondroma. Both were treated by Neodymium-YAG laser photoresection. There have been no signs of recurrence in the four years since treatment. Endobronchial resection by Neodymium-YAG laser is an effective treatment for benign endobronchial tumours.
I ain't got no body: Developmental psychology must be embodied and enactive, as well as “social”
Authors: A. P. Craig, L. Barrett
Journal: Behavioral and Brain Sciences (2004)

Although we agree with the authors' criticism of the reigning approach to children's sociocognitive development, we raise three further issues. First, “mind talk” is not, in fact, any different from the other aspects of the social world about which children learn. Second, there is no choice between either the “single mind” or the “social context.” Finally, there is a spurious separation between organism and environment.
HER2 status in breast cancer--an example of pharmacogenetic testing
Authors: M. Kroese, R. L Zimmern, S. E Pinder
Journal: Journal of the Royal Society of Medicine (2007)

The development of new drugs and associated pharmacogenetic tests will provide an increasing number of challenges to health care systems. In particular, how to evaluate their benefits, prioritize for commissioning purposes and implement a service to provide them in a timely manner. This paper presents an overview of HER2 testing for trastuzumab (Herceptin) treatment in breast cancer cases. Immunohistochemistry and fluorescence in situ hybridization laboratory techniques are described and their HER2 testing performances are compared. Future options for the national provision of HER2 testing by the National Health Service in the UK are also discussed.
C-Myc–Independent Restoration of Multiple Phenotypes by Two C-Myc Target Genes with Overlapping Functions
Authors: Krisiti Rothermund, Kenneth Rogulski, Elaine Fernandes, Amy Whiting, John Sedivy, Lixia Pu, Edward V. Prochownik
Journal: Cancer Research (2005)

Abstract C-MYC, a transforming oncogene that is frequently overexpressed in many human cancers, regulates a variety of normal functions including cell cycle progression, apoptosis, and maintenance of cell size, morphology, and genomic integrity. Many target genes are modulated by c-Myc, and some can recapitulate a limited number of the above functions. Because most of these have been assessed in cells which also express endogenous c-Myc, however, it is not clear to what extent its proper regulation is also required. We show here that, in c-Myc nullizygous cells, two direct target genes, MT-MC1 and HMG-I, could each recapitulate multiple c-Myc phenotypes. Although these differ somewhat for the two genes, substantial overlap and cooperativity exist. The enforced expression of these two genes was also associated with the differential deregulation of some previously described c-Myc target genes, indicating the presence of a complex molecular circuitry. These observations argue that, despite the great diversity of gene regulation by c-Myc, many, although not all, of its functions can be phenocopied by a small subset of key downstream target genes. The approach described here should permit the identification of other target genes capable of further c-Myc–independent complementation.
The Extracellular Matrix Glycoprotein Tenascin-C Is Beneficial for Spinal Cord Regeneration
Authors: Jian Chen, Hyun Joon Lee, Igor Jakovcevski, Ronak Shah, Neha Bhagat, Gabriele Loers, Hsing-Yin Liu, Sally Meiners, Grit Taschenberger, Sebastian Kügler, Andrey Irintchev, Melitta Schachner
Journal: Molecular Therapy (2010)

Tenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC(-/-)) mice in comparison to wild-type (TNC(+/+)) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC(-/-) mice was normalized to TNC(+/+) levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury.
Clostridium difficile infection in the community: a zoonotic disease?
Authors: M.P.M. Hensgens, E.C. Keessen, M.M. Squire, T.V. Riley, M.G.J. Koene, E. de Boer, L.J.A. Lipman, E.J. Kuijper
Journal: Clinical Microbiology and Infection (2012)
Statistics notes: Cronbach's alpha
Authors: J M. Bland, D. G Altman
Journal: BMJ (1997)

Many quantities of interest in medicine, such as anxiety or degree of handicap, are impossible to measure explicitly. Instead, we ask a series of questions and combine the answers into a single numerical value. Often this is done by simply adding a score from each answer. For example, the mini-HAQ is a measure of impairment developed for patients with cervical myelopathy.1 This has 10 items (table 1)) recording the degree of difficulty experienced in carrying out daily activities. Each item is scored from 1 (no difficulty) to 4 (can't do). The scores on the 10 items are summed to give the mini-HAQ score.

View this table:

Table 1 
Mini-HAQ scale in 249 severely impaired subjects



When items are used to form a scale they need to have internal consistency. The …
Simulation-based robot-assisted surgical training: A health economic evaluation
Authors: Shabnam Rehman, Syed Johar Raza, Andrew P. Stegemann, Kevin Zeeck, Rakeeba Din, Amanda Llewellyn, Lynn Dio, Michael Trznadel, Yong Won Seo, Ashirwad J. Chowriappa, Thenkurussi Kesavadas, Kamran Ahmed, Khurshid A. Guru
Journal: International Journal of Surgery (2013)

To determine the overall cost effectiveness of surgical skills training on Robotic Surgical Simulator (RoSS). This study evaluates the cost analysis of utilizing RoSS for robot-assisted surgical training, at Roswell Park Center for Robotic Surgery. Trainees were queried for time spent on the RoSS console over a period of 1 year, starting from June 2010 to June 2011. Time spent was converted to training time consumed on robotic console, resulting in loss of OR time and revenue. The mechanical durability of the RoSS was also determined. 105 trainees spent 361 h on the RoSS. This duration converted to 73 robot-assisted radical prostatectomy cases, and 72 animal lab sessions. RoSS prevented a potential loss of $600,000, while 72 animal labs would have cost more than $ 72,000 without including initial robot installation, annual maintenance and personnel expenses. The mechanical durability testing determined breakdown at 180 and 360 h for master control and pinch device, which were repaired under warranty. RoSS is a cost effective surgical simulator for implementation of a simulation-based robot-assisted surgical training program.
Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice
Authors: Neta Barashi, Ido D. Weiss, Ori Wald, Hanna Wald, Katia Beider, Michal Abraham, Shiri Klein, Daniel Goldenberg, Jonathan Axelrod, Eli Pikarsky, Rinat Abramovitch, Evelyne Zeira, Eithan Galun, Amnon Peled
Journal: Hepatology (2013)

Human hepatocellular carcinoma (HCC) is an inflammation-induced cancer, which is the third-leading cause of cancer mortality worldwide. We investigated the role of the chemokine receptors, CCR5 and CCR1, in regulating inflammation and tumorigenesis in an inflammation-induced HCC model in mice. Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mice spontaneously develop chronic cholestatic hepatitis and fibrosis that is eventually followed by HCC. We generated two new strains from the Mdr2-KO mouse, the Mdr2:CCR5 and the Mdr2:CCR1 double knockouts (DKOs), and set out to compare inflammation and tumorigenesis among these strains. We found that in Mdr2-KO mice lacking the chemokine receptor, CCR5 (Mdr2:CCR5 DKO mice), but not CCR1 (Mdr2:CCR1 DKO), macrophage recruitment and trafficking to the liver was significantly reduced. Furthermore, in the absence of CCR5, reduced inflammation was also associated with reduced periductal accumulation of CD24+ oval cells and abrogation of fibrosis. DKO mice for Mdr2 and CCR5 exhibited a significant decrease in tumor incidence and size. Conclusions: Our results indicate that CCR5 has a critical role in both the development and progression of liver cancer. Therefore, we propose that a CCR5 antagonist can serve for HCC cancer prevention and treatment. (Hepatology 2013;53:1021–1030)