tbuckley/cabot-search huggingface dataset:
Clinical biomarkers in resectable NSCLC
Authors: B. Khan
Journal: Thorax (2010)

In the last decade there have been small but real advances in the understanding and management of non-small cell lung cancer (NSCLC), with targeted treatments being a key innovation.

Hypoxia-induced upregulated tissue expression of carbonic anhydrase IX (CAIX) and elevated plasma CAIX levels are associated with more aggressive …
Regularization and Stylization of Medical Records
Authors: Burgess L. Gordon
Journal: JAMA (1970)

Medical documentation and transmission are impaired because of failures in the selection and tabulation of significant data at the source. Excessive narrative and lack of preciseness and specificity in the presentations pose serious difficulties in reference and interpretation. Suggestions for improvement evolved during the development of computer-oriented Current Medical Information and Terminology (CMIT). The Medical Record Form (MRF) is patterned after CMIT worksheets as used in the preparation of abstracts of textbooks and specialty journals . CMIT methodology is adaptable for MRF purposes, ie, in developing effective summaries of basic medical records to complement the original record, and to serve as input for computerization such as storage, indexing, retrieval, matching, differential diagnosis, and possible applications in data base development .
Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration
Authors: R Shaw
Journal: Cardiovascular Research (1997)

Objective: To study the ionic mechanisms of electrophysiologic changes in cell excitability and action potential duration during the acute phase of myocardial ischemia. Methods: Using an ionic-based theoretical model of the cardiac ventricular cell, the dynamic LRd model, we have simulated the three major component conditions of acute ischemia (elevated [K]o, acidosis and anoxia) at the level of individual ionic currents and ionic concentrations. The conditions were applied individually and in combination to identify ionic mechanisms responsible for reduced excitability at rest potentials, delayed recovery of excitability, and shortened action potential duration. Results: Increased extracellular potassium ([K]o) had the major effect on cell excitability by depolarizing resting membrane potential (Vrest), causing reduction in sodium channel availability. Acidosis caused a [K]o-independent reduction in maximum upstroke velocity, (dVm/dt)max. A transition from sodium-current dominated to calcium-current dominated upstroke occurred, and calcium current alone was able to sustain the upstroke, but only after sodium channels were almost completely (97%) inactivated. Acidic conditions prevented the transition to calcium dominated upstroke by acidic reduction of both sodium and calcium currents. Anoxia, simulated by lowering [ATP]i and activating the ATP-dependent potassium current, IK(ATP), was the only process that could decrease action potential duration by more than 50% and reproduce AP shape changes that are observed experimentally. Acidic or anoxic depression of the L-type calcium current could not reproduce the observed action potential shape changes and APD shortening. Delayed recovery of excitability, known as 'post-repolarization refractoriness', was determined by the voltage-dependent kinetics of sodium channel recovery; Vrest depolarization caused by elevated [K]o increased the time constant of (dVm/dt)max recovery from τ = 10.3 ms at [K]o=4.5 mM to τ = 81.4 ms at [K]o=12 mM, reflecting major slowing of sodium-channel recovery. Anoxia and acidosis had little affect on τ. Conclusions: The major conditions of acute ischemia, namely elevated [K]o, acidosis and anoxia, applied at the ionic channel level are sufficient to simulate the major electrical changes associated with ischemia. Depression of membrane excitability and delayed recovery of excitability in the single, unloaded cell are caused by elevated [K]o with additional excitability depression by acidosis. Major changes in action potential duration and shape can only be accounted for by anoxia-dependent opening of IK(ATP).
Detection and analysis of replicating hepatitis C virus RNA in hepatocellular carcinoma tissues
Authors: Masayuki Kurosaki, Nobuyuki Enomoto, Naoya Sakamoto, Yujiro Tanaka, Liang Tang, Yuji Hoshino, Namiki Izumi, Fumiaki Marumo, Chifumi Sato
Journal: Journal of Hepatology (1995)
Diseases of the alimentary system. Anorexia and loss of weight.
Authors: C Hawkins
Journal: BMJ (1976)

approach to the management of patients with head injuries admitted to hospital.Routine investigation of selected groups of patients may lead to an earlier diagnosis of traumatic intra- cranial lesions.This need not necessarily lean to an increase in the number of patients undergoing operation but, we hope, in appropriate cases, to earlier and more successful surgery.We gratefully acknowledge the collaboration of the division of neuroradiology, not only in the conduct of this study but in obtaining the original scans in the trying circumstances associated with the admission of acute head injuries.We also thank Professor Bryan Jennett for his interest and advice.
Inflammatory bowel disease and ankylosing spondylitis associated with cutaneous vasculitis, glomerulonephritis, and circulating IgA immune complexes.
Authors: A.J Peeters, A.W van den Wall Bake, M.R Daha, F.C Breeveld
Journal: Annals of the Rheumatic Diseases (1990)

Two patients both with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) developed leucocytoclastic vasculitis of the skin and nephropathy. Immunofluorescence studies showed that there was perivascular deposition of immunoglobulin A in the skin biopsy specimens of both patients and in the renal mesangium of one patient. Serum samples of the two patients contained IgA immune complexes. The absence of previous reports on such a combination of symptoms in IBD or AS suggests that these patients may have a disease entity which is distinct from uncomplicated IBD or AS, and which may combine the immunopathological features of both underlying disorders.
Noise-enhanced postural stability in subjects with functional ankle instability: Table 1
Authors: Scott E Ross
Journal: British Journal of Sports Medicine (2007)

Objective: To examine the effects of stochastic resonance (SR) stimulation on the postural stability of subjects with functional ankle instability (FAI). Design: Experimental research design. Setting: Sports medicine research laboratory. Participants: 12 subjects with FAI who reported a history of recurrent ankle sprains and “giving way” sensations at the ankle. Interventions: Subjects performed 20 s single-leg balance tests under SR stimulation at 0.05 mA and 0.01 mA and under control conditions. Testing order was randomised. Stimulators that delivered subsensory stimulation to ankle muscles and ligaments were worn. Subjects were blinded to the test conditions, as SR stimulation was subsensory and stimulators were turned off during the control condition. Main outcome measures: Anterior/posterior and medial/lateral centre-of-pressure velocities (COPVs) were combined to form a resultant vector (COPV-R). The COPV-R differences between the optimal SR stimulation and control conditions were analysed. Optimal SR stimulation was defined as the SR stimulation input intensity level (0.05 mA or 0.01 mA) that produced the greatest percentage improvement in postural stability compared with the control condition. Slower velocities indicated enhanced postural stability. Results: The optimal input intensity was 0.05 mA for nine subjects and 0.01 mA for the other three. The optimal SR stimulation significantly (p&lt;0.05) improved COPV-R compared with the control condition (6.60 (1.06) vs 7.20 (1.03) cm/s; mean (SD)). Conclusion: SR stimulation may enhance signal detection of sensorimotor signals associated with postural stability. This result has clinical relevance as improvements in postural instability associated with FAI may decrease ankle sprain injury.
Saving carbon and money
Authors: F. Godlee
Journal: BMJ (2012)

There’s a certain irony in healthcare’s substantial contribution to greenhouse gas emissions, given that climate change has been called the greatest threat to public health of the 21st century. The UK is among the world’s lowest carbon emitters relative to gross domestic product, says John Appleby (doi:10.1136/bmj.e376), and is also the only country committed to a legally binding reduction in emissions of 80% by 2050. So that’s something to feel good about. Except that it’s going to be a huge challenge, and healthcare is going to have to play its part.

Ray Moynihan describes how patients and professionals are taking the initiative, trying to save both carbon and money (doi:10.1136/bmj.d8360). An NHS …
Abstract 1806: The indolocarbazole derivative Go6976 suppresses the growth of leukemia cells with FLT3 mutations
Authors: Akira Yoshida, Kouichi Zokumasu, Takanori Ueda
Journal: Cancer Research (2012)

Abstract The FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase involved in hematopoietic progenitor cell development. Mutations of FLT3 have been reported in about a third of patients with acute myeloid leukemia (AML), and inhibitors of FLT3 are of clinical interest. Go6976 is an indolocarbazole inhibitor of the calcium-dependent isozymes of protein kinase C (PKC). In the present study, we demonstrated that Go6976 possesses a potent inhibitory activity against recombinant FLT3 using in vitro kinase assay. We also showed that Go6976 is a potent inhibitor of Aurora-B kinase. Go6976 significantly inhibited proliferation of leukemia MV4-11 cells having FLT3-internal tandem duplication (ITD). Cell growth inhibition by Go6976 occurred in parallel with the drug inhibiting FLT3 and its downstream signal pathways such as extracellular signal-regulated kinase1/2, STAT-5 and p38. The FLT3-independent myeloid leukemia HL-60 and U937 showed strong resistance to Go6976 treatment. Induction of massive apoptosis were observed upon treatment with Go6976 in MV4-11 cells associated with significant down-regulation with Survivin and Mcl-1 protein. Interestingly, Go6976 treatment also inhibited Survivin phosphorylation on Thr34, which is critical for its anti-apoptotic activity. This inhibition of Survivin phosphorylation occurred due to the direct suppression of Aurora-B by Go6976 treatment. These data indicate that Go6976 may have a unique therapeutic potential for patients with FLT3-driven leukemias. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1806. doi:1538-7445.AM2012-1806
Detection of Pelvic Deep Vein Thrombosis by Subcutaneous Radionuclide Venography Utilizing an Acupuncture Point
Authors: NAN-TSING CHIU, CHUNG-CHIENG WU, WEI-JEN YAO, KUO-FANG CHANG
Journal: Clinical Nuclear Medicine (1995)

The authors present a case of thrombosis involving the right common iliac vein evaluated with subcutaneous radionuclide venography (SCRNV) after injection at acupuncture points. SCRNV demonstrated interruption of venous flow to the right common femoral vein and right iliac vein with prominent collateral venous drainage into the contralateral deep veins. This technique, which is technically simple and relatively operator-independent, has the potential to become a screen or follow-up test for deep vein thrombosis.
SOME REMARKS ON THE MANAGEMENT OF VALVULAR CARDIAC DISEASE.
Authors: GEORGE L. COLE
Journal: JAMA (1896)

manufactures or produces defective blood cells or leucocytes.These leucocytes, following the general law of physiology, are either encysted or destroyed by the organism.When from any cause the blood- forming organs produce defective cells they are treated like other extraneous or foreign substances and de- stroyed, encapsulated or extruded.In the diseases mentioned this is, in all probability, the case; the imperfect leucocytes are extruded into the tissues and at different localities, such as the lungs, form nodules of dying or dead cells.These nodules set up a low grade of inflammatory reaction which may continue until infected by the bacilli or cast off by expectoration or destroyed by the phagocytes.Under these conditions the foci are present and constitute the same kind of pathologic seats as those following inflammatory dis- eases.
New horizons in medical ethics. Research investigations in children.
Authors: A W Franklin, A M Porter, D N Raine
Journal: BMJ (1973)

When, in the Declaration of Helsinki,' the doctor declares that "the Health of my Patient will be my first consideration," he does not abjure other considerations.His proper ambitions to enlarge his knowledge and to perfect his skills may lead him to practise medicine, not only as an art, but also as a scientific exercise, and as a result to make himself and his colleagues better doctors.He does not abjure either the laudable desire for fame and fortune, nor the somewhat less laudable pleasure that arises from the exercise of power.He should, however, recognize how these strong feelings may influence his judgement.The Declaration allows clinical research to be combined with professional care if there is therapeutic value for the patient, which is spelled out as saving life, re-establishing health, and alleviating suffering.The Medical Research Council2 widens the scope and seems to allow indirect as well as direct benefits for the actual patient by adding prevention of disease and "increased understanding of his case."Provided that he is not negligent, the registered doctor may hurt, maim by surgery, poison by drugs, or even bring about the death of his patient without penalty.The tacit understanding
Postmenopausal Hormone Replacement
Authors: Sally E. McNagny
Journal: Annals of Internal Medicine (1998)

Letters15 July 1998Postmenopausal Hormone ReplacementSally E. McNagny, MD, MPH, Nanette K. Wenger, MD, and Erica Frank, MD, MPHSally E. McNagny, MD, MPHEmory University; Atlanta, GA 30303Search for more papers by this author, Nanette K. Wenger, MDEmory University; Atlanta, GA 30303Search for more papers by this author, and Erica Frank, MD, MPHEmory University; Atlanta, GA 30303Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-2-199807150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Panico and colleagues predict that if the rate of death from ischemic heart disease continues to decrease, mortality rates for ischemic heart disease and breast cancer will become equivalent for U.S. women 50 to 70 years of age by 2008. From a population-based perspective, the greatest benefit of HRT is hypothesized to be cardiovascular risk reduction, and the greatest risk is an increase in breast cancer; therefore, a decrease in mortality from ischemic heart disease could greatly affect the risk–benefit ratio. This line of reasoning is interesting and potentially important, but we do not believe it is relevant ...References1. Nelson DE, Giovino GA, Emont SL, Brackbill R, Cameron LL, Peddicord J, et al. Trends in cigarette smoking among US physicians and nurses. JAMA. 1994; 271:1273-5. Google Scholar Author, Article, and Disclosure InformationAuthors: Sally E. McNagny, MD, MPH; Nanette K. Wenger, MD; Erica Frank, MD, MPHAffiliations: Emory University; Atlanta, GA 30303 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1998Volume 129, Issue 2 Page: 161 Keywords Behavior Breast cancer Cardiovascular disease risk Cardiovascular therapy Death rates Mortality Primary hypertension Reasoning Risk management Socioeconomic status ePublished: 15 August 2000 Issue Published: 15 July 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A c-Myc-MicroRNA functional feedback loop affects hepatocarcinogenesis
Authors: Han Han, Dan Sun, Wenjuan Li, Hongxing Shen, Yahui Zhu, Chen Li, Yuxing Chen, Longfeng Lu, Wenhua Li, Jinxiang Zhang, Yuan Tian, Youjun Li
Journal: Hepatology (2013)

Abstract c-Myc (Myc) plays an important role in normal liver development and tumorigenesis. We show here that Myc is pathologically activated in and essential for promoting human hepatocellular carcinoma (HCC). Myc induces HCC through a novel, microRNA (miRNA)-mediated feedback loop comprised of miR-148a-5p, miR-363-3p, and ubiquitin-specific protease 28 (USP28). Myc directly binds to conserved regions in the promoters of the two miRNAs and represses their expression. miR-148a-5p directly targets and inhibits Myc, whereas miR-363-3p destabilizes Myc by directly targeting and inhibiting USP28. Inhibition of miR-148a-5p or miR-363-3p induces hepatocellular tumorigenesis by promoting G1 to S phase progression, whereas activation of them has the opposite effects. The Myc-miRNA feedback loop is dysregulated in human HCC. Conclusion: These results define miR-148a-5p and miR-363-3p as negative regulators of Myc, thus revealing their heretofore unappreciated roles in hepatocarcinogenesis.
Abstract 1051: Atypical PKC and TGFβ receptors co-operate to phosphorylate Par6
Authors: Adrian Gunaratne, John Di Guglielmo
Journal: Cancer Research (2011)

Abstract Transforming growth factor beta (TGFβ) is involved in many aspects of cellular behavior including apoptosis and differentiation. In tumor cells, TGFβ signaling alters cell plasticity through a loss in apical-basal cell polarity and induces epithelial to mesenchymal transition (EMT). Integral to this process is the phosphorylation of a polarity protein, Par6, on a conserved serine residue (S345). Recent work has shown that phosphorylation of this site not only increases cell plasticity and EMT, but also promotes an invasive phenotype in breast cancer cells. Our work suggests that a polarity partner of Par6, atypical Protein Kinase C (aPKC), can also phosphorylate Par6 on this critical site to drive distinct cellular changes in non-small cell lung cancer (NSCLC) cells. Using co-immunoprecipitation studies and immunofluorescence microscopy, we show that aPKCι interacts with TGFβ receptors through the adaptor Par6, and that these proteins localize to the leading edge of migrating cells. Furthermore, co-expression of Par6 with TGFβ receptors results in increased phospho-Par6 levels as previously reported. However, we have also found that phosphorylation of Par6 increases in the presence of aPKC. aPKC kinase activity as well as association with Par6 were found to be important for Par6 phosphorylation as evidenced by a loss in phospho-Par6 using a kinase deficient mutant of PKCζ (PKCζ -KR) as well as a mutant of Par6 that does not bind aPKC (Par6-K19A). Furthermore, gene silencing of atypical PKC reduces TGFβ induced cell morphology changes, E-cadherin loss, and stress fiber production. Finally, gene silencing of atypical PKC was observed to reduce TGFβ dependent migration of NSCLC cells. In conclusion, our results indicate that atypical PKC cooperate with TGFβ receptors to regulate phospho-Par6 levels to drive an invasive phenotype of NSCLC cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1051. doi:10.1158/1538-7445.AM2011-1051
The cardiac and hemodynamic effects of insulin on non-diabetic American Indians: the strong heart study
Authors: A. Ilercil, M.J. Roman, M. Paranicas, M.J. O'Grady, T.K. Welty, R.R. Fabsitz, B.V. Howard, E.T. Lee, R.B. Devereux
Journal: Journal of the American College of Cardiology (1998)
The Problem of the Placebo Response in Clinical Trials for Psychiatric Disorders: Culprits, Possible Remedies, and a Novel Study Design Approach
Authors: Maurizio Fava, A. Eden Evins, David J. Dorer, David A. Schoenfeld
Journal: Psychotherapy and Psychosomatics (2003)

The placebo response is a major issue in clinical trials for psychiatric disorders. Possible contributing factors to this problem include diagnostic misclassification, issues concerning inclusion/exclusion criteria, outcome measures’ lack of sensitivity to change, measurement errors, poor quality of data entry and verification, waxing and waning of the natural course of illness, regression toward the mean phenomenon, patient and clinician expectations about the trial, study design issues, non-specific therapeutic effects, and high attrition. Over the past few decades, researchers have attempted to reduce the placebo effect in a variety of ways. Unfortunately, approaches with very little or no benefit have included restricting enrollment to selected populations, rater training, requirement of same rater, and placebo lead-in phases. Some benefits, although often marginal, have been derived from standardizing diagnostic procedures, managing clinicians’ overestimation of change, simplification of study visits and assessments, minimizing non-specific, therapeutic effects, extending trial duration, reducing number of sites, increasing the sensitivity of outcome measures, and reducing the number of treatment arms. Thus far, there has been no attempt to develop new study designs aimed at reducing the placebo effect. We are proposing a novel study design, called ‘Sequential Parallel Comparison Design’, suitable for double-blind, placebo-controlled trials in psychiatric disorders. This design is aimed at reducing both the overall placebo response rate and the sample size required for such trials. Its usefulness in clinical research needs to be tested empirically. If this study design were to be found to meet its stated goals, this could markedly facilitate the process of clinical development of new compounds for the treatment of psychiatric disorders.
Histology simulating reticulosis in secondary syphilis
Authors: REBECCA E.I. COCHRAN, JOHN THOMSON, K.A. FLEMING, ALEXANDRA M.M. STRONG
Journal: British Journal of Dermatology (1976)

Three cases of secondary syphilis are described in whom a skin biopsy was performed. In all, the histology bore a striking resemblance to that of malignant lymphoid neoplasm. The classical cutaneous manifestations of secondary syphilis are usually easy to diagnose, especially when there is a good clinical history and the appropriate investigations are positive. If, however, the eruption is not characteristic, a skin biopsy may be carried out. We should like to report three cases where the histological appearances in isolation would have been misleading.
HYPOTHESIS‐DETERMINANT FACTORS IN THE MANIFESTATIONS OF ATOPIC DISEASE
Authors: GEORGE W. BRASHER
Journal: Allergy (1977)

It is postulated that both the initiation and the perpetuation of atopic disease occur as a result of a complex interaction of a genetically determined IgE response, increased permeability of the gastrointestinal and respiratory tracts, and an inherent metabolic instability that may be either localized or generalized. These three factors vary as a function of age and serve to explain the complicated natural history of allergic manifestations in atopic persons.