tbuckley/cabot-search huggingface dataset:
Abstract 3202: Deciphering the targets and mechanism of action of the natural product Tonantzitlolone in clear cell renal cell carcinomas
Authors: Carole Sourbier, Brad Scroggins, Philip Z. Mannes, John A. Beutler, W. Marston Linehan, Len Neckers
Journal: Cancer Research (2014)

Abstract Tonantzitlolone is a diterpene ester first extracted in 1990 from the native Mexican plant Stillingia sanguinolutea (Euphorbiaceae), which displays anti-tumor activity. Although its structure and total synthesis have been elucidated, its cellular target(s) and potential mechanism of action remain unknown. We identified Tonantzitlolone as a dual PKCα and PKCθ activator in vitro. However in clear cell renal cell carcinoma (CCRCC), its activity was mostly PKCθ-dependent. Through activation of PKCθ, Tonantzitlolone induced an insulin-resistant phenotype by inhibiting IRS1 and the PI3K/Akt pathway. Simultaneously, Tonantzitlolone activated the transcription factor heat shock factor 1 (HSF1), driving glucose dependency. Thus, similar to the selective PKCθ activator Englerin A, Tonantzitlolone induces a metabolic catastrophe in CCRCC, starving the cells of glucose while increasing their glycolytic dependency, ultimately leading to cell death. Citation Format: Carole Sourbier, Brad Scroggins, Philip Z. Mannes, John A. Beutler, W. Marston Linehan, Len Neckers. Deciphering the targets and mechanism of action of the natural product Tonantzitlolone in clear cell renal cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3202. doi:10.1158/1538-7445.AM2014-3202
A pharmacological effect of oestrone on human epidermis
Authors: P. SHAHRAD, R. MARKS
Journal: British Journal of Dermatology (1977)

Journal Article A pharmacological effect of oestrone on human epidermis Get access P. SHAHRAD, P. SHAHRAD Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff Search for other works by this author on: Oxford Academic Google Scholar R. MARKS R. MARKS Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff Dr R.Marks, Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 4, 1 October 1977, Pages 383–386, https://doi.org/10.1111/j.1365-2133.1977.tb14245.x Published: 01 October 1977
MULTIPURPOSE BRACE: A USEFUL ADJUNCT IN REHABILITATION
Authors: William Benham Snow
Journal: JAMA (1952)

This multipurpose brace consists of two tubular lateral bars, both of which are adjustable in length. The adjustment is simple, speedy, and secure, without any screw attachments or special tools. The upper end of the brace consists of a half ring, padded and leather covered, which can tilt laterally to accommodate to the lengthening of either side bar. The lower ends of the side bars fit on a narrow flat metal bar covered with a thin weight bearing rubber pad. This is placed anterior to the heel of the shoe and can be strapped in place. There are padded straps attached to the side bars to serve as supports for the calf and thigh, as is usual in permanent braces. An ingenious knee pad can be strapped anterior to the patella. The half ring at the thigh can serve as the upper end of the brace if the side bars
Shoe-fitting by X-rays
Authors: W. G. Booth
Journal: BMJ (1956)

That investors should diversify their portfolios is a core principle of modern finance. Yet there are some periods in which diversification is undesirable. When the portfolio’s main growth engine performs well, investors prefer the opposite of diversification. An ideal complement to the growth engine would provide diversification when it performs poorly and unification when it performs well. Numerous studies have presented evidence of asymmetric correlations between assets. Unfortunately, this asymmetry is often of the undesirable variety: It is characterized by downside unification and upside diversification. In other words, diversification often disappears when it is most needed. In this article, the authors highlight a fundamental flaw in the way some prior studies have measured correlation asymmetry. Because they estimate downside correlations from subsamples in which both assets perform poorly, they ignore instances of successful diversification (i.e., periods in which one asset’s gains offset the other’s losses). The authors propose instead that investors measure what matters: the degree to which a given asset diversifies the main growth engine when it underperforms. This approach yields starkly different conclusions, particularly for asset pairs with low full-sample correlation. The authors review correlation mathematics, highlight the flaw in prior studies, motivate the correct approach, and present an empirical analysis of correlation asymmetry across major asset classes. <b>TOPICS:</b>Portfolio theory, portfolio construction, quantitative methods, statistical methods, performance measurement <b>Key Findings</b> ▪ There is strong empirical evidence that asset class correlations are asymmetric, which poses complications in portfolio construction. ▪ Investors prefer diversification when a portfolio’s main growth engine performs poorly and unification when it performs well. ▪ To measure correlation asymmetry caused by nonnormality, investors must adjust for changes in correlation that arise mathematically when part of a sample is excluded. ▪ Unlike prior research, investors should condition correlations on the performance of a single asset, not two assets.
France abandons fines to control health costs
Authors: A. Dorozynski
Journal: BMJ (1999)

A key plank in the French government's plans to control health costs-the introduction of collective fines for doctors spending more than their allocated budgets-has been halted after being judged unconstitutional.

The Conseil Constitutionnel, the body ruling on the constitutionality of parliamentary procedures and legislation in France, has judged that a planned system of collective fines for doctors if their health spending exceeds the annual amount budgeted by parliament …
Urine Biomarkers Predict the Cause of Glomerular Disease
Authors: Sanju A. Varghese, T. Brian Powell, Milos N. Budisavljevic, Jim C. Oates, John R. Raymond, Jonas S. Almeida, John M. Arthur
Journal: Journal of the American Society of Nephrology (2007)

Diagnosis of the type of glomerular disease that causes the nephrotic syndrome is necessary for appropriate treatment and typically requires a renal biopsy. The goal of this study was to identify candidate protein biomarkers to diagnose glomerular diseases. Proteomic methods and informatic analysis were used to identify patterns of urine proteins that are characteristic of the diseases. Urine proteins were separated by two-dimensional electrophoresis in 32 patients with FSGS, lupus nephritis, membranous nephropathy, or diabetic nephropathy. Protein abundances from 16 patients were used to train an artificial neural network to create a prediction algorithm. The remaining 16 patients were used as an external validation set to test the accuracy of the prediction algorithm. In the validation set, the model predicted the presence of the diseases with sensitivities between 75 and 86% and specificities from 92 to 67%. The probability of obtaining these results in the novel set by chance is 5 x 10(-8). Twenty-one gel spots were most important for the differentiation of the diseases. The spots were cut from the gel, and 20 were identified by mass spectrometry as charge forms of 11 plasma proteins: Orosomucoid, transferrin, alpha-1 microglobulin, zinc alpha-2 glycoprotein, alpha-1 antitrypsin, complement factor B, haptoglobin, transthyretin, plasma retinol binding protein, albumin, and hemopexin. These data show that diseases that cause nephrotic syndrome change glomerular protein permeability in characteristic patterns. The fingerprint of urine protein charge forms identifies the glomerular disease. The identified proteins are candidate biomarkers that can be tested in assays that are more amenable to clinical testing.
Typhoid Fever Obscured by Inadequate Chlortetracycline Therapy
Authors: Philip R. Steinmetz
Journal: New England Journal of Medicine (1959)

IT is usually possible to rule out typhoid fever in the differential diagnosis of a fever of unknown origin in the first few weeks. Culture methods are likely to demonstrate the organism in the blood and some time later in the stool or urine. In the third week the rise in serum agglutinins may be significant enough to help the clinician who entertained the diagnosis on epidemiologic and clinical grounds but had been unable to isolate the typhoid bacillus.A case of severe typhoid fever in which neither a clinical nor a bacteriologic diagnosis could be made for more than . . .
Objective Evaluation of Endoscopy Skills during Training
Authors: Oliver W. Cass, Martin L. Freeman, Craig J. Peine, Richard T. Zera, Gerald R. Onstad
Journal: Annals of Internal Medicine (1993)

To evaluate the number of supervised gastrointestinal endoscopic procedures required to achieve initial competency using a simple objective grading system.Prospective, cross-sectional study.A gastroenterology and surgical training program at a large, university-affiliated county hospital.Seven gastroenterology fellows and five fourth-year surgery residents.Trainees were graded postprocedure using a microcomputer program. Grading criteria for esophagogastroduodenoscopy included entering the esophagus (esophageal intubation), traversing the pylorus into the duodenum, and recognizing whether the upper gastrointestinal tract was abnormal. Criteria for colonoscopy were traversing the splenic flexure, intubating the cecum, and recognizing whether the colon was abnormal.When presented with a case mix representative of practice, esophageal intubation did not reach 90% until more than 100 procedures had been done. Cecal intubation remained at only 84% after 100 procedures.More than 100 supervised upper gastrointestinal endoscopies or colonoscopies are necessary to achieve technical competence in gastrointestinal endoscopy.
A BRIEF REPORT OF THE NEBRASKA EPIDEMIC OF POLIOMYELITIS
Authors: H. M. McCLANAHAN
Journal: JAMA (1910)

This epidemic occurred during the summer of 1909. In proportion to the population it was greatly more extensive than the epidemic in New York City of 1907. My report is based on personal letters received from fifty-eight physicians, a number of whom I have seen personally. I have been greatly aided by Drs. H. W. Orr and W. H. Wilson of Lincoln, Nebraska, and hereby acknowledge my appreciation of their courtesy. Dr. Orr investigated the epidemic with a view to determining chiefly the nature and extent of the resulting paralysis. His paper was recently read before the American Orthopedic Society. Dr. Orr wrote directly to the people and received replies from 213 families, reporting on 345 cases. The total number of cases reported to him was 619. A brief summary is as follows: Fully recovered, 151; not reported, 195; died, 91; one arm affected, 21: one leg, 53; side, 7; both
Abstract 4803: Cancer-associated fibroblast promotes gastric cancer invasion and epithelial-mesenchymal transition via the IL-6/JAK/STAT3 signaling pathway
Authors: Liping Su, Xiongyan Wu, Quan Zhou, Chenchen Wang, Bingya Liu
Journal: Cancer Research (2014)

Abstract Objectives: The molecular mechanisms involved in the regulation of gastric cancer progression by CAFs are still unclear. The aim of the present study was to determine if CAFs can enhance the tumor epithelial-to-mesenchymal transition (EMT) and invasion of gastric cancer cells, and link CAFs with activation of the IL-6/JAK/ STAT3 signaling pathway in the progression of gastric cancer. Methods: Fibroblasts were isolated from gastric cancer. The identification of CAFs was defined by immunofluorescence staining and qRT-PCR. IL-6 expression in CAFs and gastric cancer cells was detected by qRT-PCR and ELISA. EMT and activation of Stat3 pathway in gastric cancer cells were detected by realtime PCR and western blot. Cell invasion assays were performed by using 8 μm transwell chambers. Results: IL-6 expression in gastric cancer tissue was significantly higher than that in adjacent non-tumor tissue (3.450ng/g vs 2.665ng/g,P&amp;lt;0.01). Using real time RT-PCR and ELISA, we found IL-6 expression was significantly higher in CAFs compared to that in gastric cancer cells. Co-culture with CAFs in a transwell system induced EMT of gastric cancer cells, which was demonstrated by decreased expression of E-cadherin and α-catenin, and increased expression of Twist1, MMP2 and ZEB2. However, deprivation of IL-6 using a neutralizing antibody or inhibition Stat3 activation with AG490 impaired the EMT of gastric cancer cells. Gastric cancer cells co-cultured with CAFs showed enhanced ability of migration and invasion than gastric cancer cells alone. However, adding neutralizing IL-6 antibody or AG490 into the co-culture system led to significantly decreased invasion (P &amp;lt; 0.05) of SGC-7901 cells. Moreover, IL-6 secreted from CAFs activated the JAK/STAT3 pathway in gastric cancer cells, however, EMT and invasion of gastric cancer cells was inhibited when IL-6/JAK/STAT3 pathway was blocked. Conclusions: CAFs induced EMT and invasion of gastric cancer cells through activation of the IL-6/JAK/STAT3 pathway. Citation Format: Liping Su, Xiongyan Wu, Quan Zhou, Chenchen Wang, Bingya Liu. Cancer-associated fibroblast promotes gastric cancer invasion and epithelial-mesenchymal transition via the IL-6/JAK/STAT3 signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4803. doi:10.1158/1538-7445.AM2014-4803
Modernising the NHS: Patient care: access
Authors: M. Murray
Journal: BMJ (2000)

This is the fifth of seven articles 

Delays for access to care plague our healthcare systems. These delays cause patient dissatisfaction, contribute to staff dissatisfaction, and may lead to worsening clinical outcomes. They are also expensive: patients often consume scarce resources while waiting, there is a cost in maintaining any waiting list; the longer the wait the higher the “fail to show” rate, which represents unused capacity; and, finally, there is the risk that patients waiting will arrive with a more costly clinical condition.

Access to care can be improved. Improving access involves looking at system flexibility or capacity. There are three fundamental methods of gaining capacity in a system of care.

#### Summary points

Delays plague all healthcare systems, causing discontent, consuming resources, and worsening clinical outcomes

Most waiting systems rely on distinguishing between urgent and routine cases and so maintain two queues

Real improvements in access come about when there is only one queue and it is short enough to ensure prompt treatment for urgent cases

Improving access involves determining the demand and applying resources to match it or reduce it

Firstly, many current systems are characterised by schedules that are filled far in advance of the delivery of care or service. Demand arises from the population served. This demand is generally stratified into “urgent” and “routine” queues. Urgent demand is managed by overfilling an already saturated schedule or by sending that demand to another venue for resolution. Routine demand is put to the end of the queue. Overfilling a full schedule or sending demand to another venue or to the end of the queue infuriates patients, overburdens providers of care, and often just postpones the needed care or service.

Secondly, other systems gain capacity by predicting demand for urgent care or service and holding capacity in anticipation of this need. …
Effect of pentoxifylline on early proliferation and phenotypic modulation of fibrogenic cells in two rat models of liver fibrosis and on cultured hepatic stellate cells
Authors: Alexis Desmoulière, Guoxiong Xu, Andréa M.A Costa, Ibrahim M Yousef, Giulio Gabbiani, Beatriz Tuchweber
Journal: Journal of Hepatology (1999)
Breastfeeding in Women With Epilepsy
Authors: Paul C. Van Ness
Journal: JAMA Neurology (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Simple measures could save “millions” of newborns
Authors: Pat Hagan
Journal: BMJ (2001)

Millions of deaths of infants in developing countries could be prevented if governments and international agencies promoted cheap and simple measures to protect babies in the very early stages of life, according to a new report.

The report, State of the World's Newborns , argues that high death rates could be reduced by such practices as exclusive breast feeding, keeping babies warm, and ensuring that there are skilled attendants at the birth. By combining these with other measures, such as ensuring that delivery environments are hygienic and that mothers receive basic health care and advice, thousands of unnecessary deaths …
Environmental Hazards
Authors: Richard L. Woodward
Journal: New England Journal of Medicine (1966)

THE problem of water pollution is a part of many problems and a problem with many parts. It is involved in the larger question of waste management and control of environmental pollution. It is an important feature of the general problem of urban design. It is closely related to the larger problem of water resource utilization and conservation. It is, in part, a problem of public health. It has important economic aspects. It is affected by changing industrial technology and will require technologic innovation for its solution. Social and political demands and constraints have a great effect on the nature . . .
Amoebic Liver Abscess in Great Britain
Authors: J. W. Paulley
Journal: BMJ (1961)

AMOEBIC HEPATITIS BRITISIIMEDICAL JOURNAL to explain on the basis of only one case.Nevertheless, it is possible for E. histolytica to reach the ascitic fluid by the blood or lymphatic circulation or by infiltration of the peritoneum.The striking improvement in the patient's condition after anti-amoebic therapy also confirms the nature of the disease.The therapeutic test often gives the only valid evidence of amoebic disease.In explaining why no abscess developed in the liver during the long course of the disease it must be remembered that many different factors are related to the formation of the lesions of hepatic amoebiasis.Seneca (1956) mentioned that liver lesions produced by malaria, syphilis, alcohol, malnutrition, or trauma may predispose to the develop- ment of liver abscess.It must also be assumed that the majority of amoebae do not survive in the liver when the organ is intact.Summary An unusual case of chronic non-suppurative diffuse amoebic hepatitis has been described.Entamoeba histolytica was found in needle and surgical liver biopsies as well as in a liver abscess which developed in an experimental animal after injection of ascitic fluid.The mechanism of the disease process is discussed.
Induction of IFN type I biology following therapy determines clinical response to rituximab in rheumatoid arthritis
Authors: S. Vosslamber, H. G. Raterman, T. C. T. M. van der Pouw Kraan, M. W. J. Schreurs, B. M. E. von Blomberg, M. T. Nurmohamed, W. F. Lems, B. A. C. Dijkmans, A. E. Voskuyl, C. L. Verweij
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Despite the fact that rituximab depletes B cells in all treated rheumatoid arthritis (RA) patients, not all patients show a favorable clinical response. The goal of this study was to provide insight into the pharmacological changes in the peripheral blood that are associated with clinical response to rituximab using genome-wide gene expression profiling. <h3>Methods</h3> Gene-expression profiling was performed on peripheral blood RNA from 13 RA patients (test group) using Illumina HumanHT beadchip microarrays. An independent group of nine patients was used for validation using Taq-man qPCR. Clinical responder status was determined after 6 months using ΔDAS28 and EULAR response criteria. Significance analysis of microarrays, gene set enrichment analysis and metacore ontology analysis were used for data analysis and interpretation. <h3>Results</h3> Pharmacogenomic studies in 13 RA patients demonstrated marked interindividual differences in the pharmacological responses at 3 months after the start of therapy with rituximab. Interestingly, only differences in the regulation of the type I interferon (IFN) -response genes at 3 months after therapy correlated with the ΔDAS28 response. Good responders (ΔDAS &gt;1.2; n=7) exhibited a selective increase in the expression of type I IFN-response genes, whereas this activity was not or hardly changed in non-responders (ΔDAS &lt;1.2; n=6) after 3 months (p = 0.0040 at a cut-off of 0.15 fold (log2 based) induction). Similar results were obtained using EULAR response criteria. The increase in type I IFN-activity in the good responders correlated with a low baseline level. The association between an increased type I IFN-response activity and clinical response is validated in an independent cohort of nine patients (four responders and five non-responders, p = 0.0317). <h3>Conclusions</h3> A good clinical response to rituximab in RA is associated with a selective increase in type I IFN-response activity in RA patients. This finding may provide insight in the biological mechanism underlying the therapeutic response of rituximab.
Ultrashort peptide nanofibrous hydrogels for the acceleration of healing of burn wounds
Authors: Yihua Loo, Yong-Chiat Wong, Elijah Z. Cai, Chuan-Han Ang, Ashvin Raju, Anupama Lakshmanan, Alvin G. Koh, Hui J. Zhou, Thiam-Chye Lim, Shabbir M. Moochhala, Charlotte A.E. Hauser
Journal: Biomaterials (2014)
Development and initial validation of a simple clinical decision tool to predict the presence of heart failure in primary care: the MICE (Male, Infarction, Crepitations, Edema, MICE) rule
Authors: Andrea K. Roalfe, Jonathan Mant, Jenny A. Doust, Pelham Barton, Martin R. Cowie, Paul Glasziou, David Mant, Richard J. McManus, Roger Holder, Jonathan J. Deeks, Robert N. Doughty, Arno W. Hoes, Kate Fletcher, F.D. Richard Hobbs
Journal: European Journal of Heart Failure (2012)
Erratum: Corrigendum: Genomic signatures to guide the use of chemotherapeutics
Authors: Anil Potti, Holly K Dressman, Andrea Bild, Richard F Riedel, Gina Chan, Robyn Sayer, Janiel Cragun, Hope Cottrill, Michael J Kelley, Rebecca Petersen, David Harpole, Jeffrey Marks, Andrew Berchuck, Geoffrey S Ginsburg, Phillip Febbo, Johnathan Lancaster, Joseph R Nevins
Journal: Nature Medicine (2008)