tbuckley/cabot-search huggingface dataset:
Automated Quantitative Analysis (AQUA) of In Situ Protein Expression, Antibody Concentration, and Prognosis
Authors: Anthony McCabe, Marisa Dolled-Filhart, Robert L. Camp, David L. Rimm
Journal: JNCI Journal of the National Cancer Institute (2005)

Disparate results in the immunohistochemistry literature regarding the relationship between biomarker expression and patient outcome decrease the credibility of tissue biomarker studies. We investigated whether some of these disparities result from subjective optimization of antibody concentration.We used the automated quantitative analysis (AQUA) system and various concentrations of antibodies against HER2 (1 : 500 to 1 : 8000 dilutions), p53 (1 : 50 to 1 : 800 dilutions), and estrogen receptor (ER; 1 : 100 and 1 : 1000 dilutions) to assess expression of HER2 and p53 in a tissue microarray containing specimens from 250 breast cancer patients with long-term survival data available. HER2 expression in the tissue microarray was also assessed by conventional immunohistochemistry. Relative risk (RR) of disease-specific mortality was assessed for every cutpoint with the X-tile program. Cumulative disease-specific survival was assessed by the Kaplan-Meier method. All statistical tests were two-sided.For HER2 and p53 and an optimal cutpoint, when a high antibody concentration (i.e., 1 : 500 dilution) was used with the AQUA system, low expression was associated with poorer survival than high expression; however, when a low antibody concentration (i.e., 1 : 8000 dilution) was used, high expression was associated with poorer survival. For example, for a 1 : 8000 dilution of HER2 antibody and high expression defined as the top 15% of HER2 expression, high HER2 expression was associated with increased disease-specific mortality (RR = 1.98, 95% confidence interval [CI] = 1.21 to 3.23; P = .007), compared with low expression. However, for a 1 : 500 dilution of HER2 antibody and high expression defined as the top 85% of HER2 expression, high HER2 expression was associated with decreased disease-specific mortality (RR = 0.47, 95% CI = 0.29 to 0.76; P = .002), compared with low HER2 expression.Biomarker antibody concentration appears to dramatically affect the apparent relationship between biomarker expression and outcome.
PCO2 and [K+]p in Metabolic Acidosis
Authors: Horacio J. Adrogue[Combining Acute Accent], Nicolaos E. Madias
Journal: Journal of the American Society of Nephrology (2004)

Studies by Schwartz and colleagues at Tufts University School of Medicine in the 1960s described the “whole-body” acid-base response ( i.e. , secondary changes in plasma [HCO3−] to graded degrees of acute respiratory acidosis and acute respiratory alkalosis in humans ([1,2][1][⇓][2]).
The P2X7 receptor–pannexin-1 complex decreases muscarinic acetylcholine receptor–mediated seizure susceptibility in mice
Authors: Ji-Eun Kim, Tae-Cheon Kang
Journal: Journal of Clinical Investigation (2011)

Pannexin-1 (Panx1) plays a role in the release of ATP and glutamate in neurons and astrocytes. Panx1 can be opened at the resting membrane potential by extracellular ATP via the P2X7 receptor (P2X7R). Panx1 opening has been shown to induce neuronal death and aberrant firing, but its role in neuronal activity has not been established. Here, we report the role of the P2X7R-Panx1 complex in regulating muscarinic acetylcholine 1 (M1) receptor function. P2X7R knockout (P2X7–/–) mice showed greater susceptibility to seizures induced by pilocarpine (PILO), an M1 receptor agonist, than their WT littermates, despite having similar levels of hippocampal M1 receptor expression. This hypersensitivity to PILO in the P2X7–/– mice did not involve the GABA or glutamate system. Both administration of P2X7R antagonists and gene silencing of P2X7R or Panx1 in WT mice increased PILO-induced seizure susceptibility in a process mediated by PKC via intracellular Ca2+ release. Therefore, we suggest that the P2X7R-Panx1 complex may play an important role as a negative modulator of M1 receptor–mediated seizure activity in vivo.
Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model
Authors: X. Hong, L. Liu, M. Wang, K. Ding, Y. Fan, B. Ma, B. Lal, B. Tyler, A. Mangraviti, S. Wang, J. Wong, J. Laterra, J. Zhou
Journal: Neuro-Oncology (2013)

The inability of structural MRI to accurately measure tumor response to therapy complicates care management for patients with gliomas. The purpose of this study was to assess the potential of several noninvasive functional and molecular MRI biomarkers for the assessment of glioma response to radiotherapy.Fourteen U87 tumor-bearing rats were irradiated using a small-animal radiation research platform (40 or 20 Gy), and 6 rats were used as controls. MRI was performed on a 4.7 T animal scanner, preradiation treatment, as well as at 3, 6, 9, and 14 days postradiation. Image features of the tumors, as well as tumor volumes and animal survival, were quantitatively compared.Structural MRI showed that all irradiated tumors still grew in size during the initial days postradiation. The apparent diffusion coefficient (ADC) values of tumors increased significantly postradiation (40 and 20 Gy), except at day 3 postradiation, compared with preradiation. The tumor blood flow decreased significantly postradiation (40 and 20 Gy), but the relative blood flow (tumor vs contralateral) did not show a significant change at most time points postradiation. The amide proton transfer weighted (APTw) signals of the tumor decreased significantly at all time points postradiation (40 Gy), and also at day 9 postradiation (20 Gy). The blood flow and APTw maps demonstrated tumor features that were similar to those seen on gadolinium-enhanced T1-weighted images.Tumor ADC, blood flow, and APTw were all useful imaging biomarkers by which to predict glioma response to radiotherapy. The APTw signal was most promising for early response assessment in this model.
PWE-025 Post-radiotherapy pharyngeal/proximal oesophageal strictures in head and neck malignancy: outcome of endoscopic bougie dilation
Authors: R Sringeri, L Priestnall, R Cullen, N C Fisher
Journal: Gut (2012)

<h3>Introduction</h3> Chemo-radiotherapy is the standard of care for most patients with head and neck malignancy. Radiotherapy may lead to dysphagia due to pharyngeal/proximal oesophageal strictures. Endoscopic management of these strictures with antegrade dilation by using Savary Gilliard bougie dilators is described in literature.<sup>1 2</sup> Our aim was to review the outcome in patients referred for bougie dilation for radiotherapy induced strictures. <h3>Methods</h3> It is a retrospective case notes review. <h3>Results</h3> 11 patients underwent bougie dilation of radiotherapy induced strictures in last 4 years. Nine male, two female patients with median age of 71 years. Five patients had laryngeal cancer and six had oropharyngeal cancer. All patients had radiotherapy where four had concurrent chemotherapy. Five patients required flouroscopy and seven patients required nase endoscope. Median size of initial bougie size was 11 mm and final bougie size was 17 mm. Mean number of procedures per patient was 4. No complications noted. While three patients had good response, six had borderline and two had none. Median interval from completion of radiotherapy to index procedure was 2.5 years with range from 2 months to 12 years. <h3>Conclusion</h3> Savary Gilliard bougie dilation appears to be safe and well tolerated method for dilating pharyngeal/proximal oesophageal strictures secondary to radiotherapy treatment for head and neck cancer. While symptom improvement varied among patients probably early intervention might benefit the patient. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Ahlawat SK</b>, Al-Kawas FH. Endoscopic management of upper esophageal strictures after treatment of head and neck malignancy. <i>Gastrointest Endosc</i> 2008;<b>68</b>:19–24. 2. <b>Dhir V</b>, Vege SS, Mohandas KM, <i>et al.</i> Dilation of proximal esophageal strictures following therapy for head and neck cancer: experience with Savary Gilliard dilators. <i>J Surg Oncol</i> 1996;<b>63</b>:187–90.
Clinical studies in medical journals
Authors: J P Griffin
Journal: Journal of the Royal Society of Medicine (2007)

By couching the discussion of Blair and Bush in terms of hubris and nemesis, Lord Owen 1 has avoided the pitfall of diagnosis from afar while still highlighting serious problems with the two world leaders (JRSM November 2006).He does dip his toe into psychodynamics citing Freud and Justin Frank, but, by and large, he sticks to discussing behaviour and its relation to hubris and power.As a politician, Lord Owen is qualified to discuss the political leaders he has encountered.As a physician, should he be making medical judgments on political leaders?Simon Wessely has questions about this and about whether or not psychiatrists should venture beyond the consulting room. 2 Should psychiatrists limit their judgments to patients they have examined?The American Psychiatric Association says 'yes' and Dr Wessely cites data to support that view.But the question remains, can psychiatrists and neuroscientists, with the help of philosophers, provide useful insights that contribute to the understanding of leaders and their followers?I believe that we should try.We should bring whatever scientific data there may be to counter ideology, blind faith and the intoxicating effects of power.It is true hubris often comes with power.Even though we do not have a psychiatric diagnosis for hubris, it is a psychological entity and as such should potentially be understood by science, as are other psychological phenomena.We do not diagnose those that we have not personally examined and we cannot diagnose an entire population, but perhaps we can bring clinical and scientific insights to help understand destructive behaviour As scientists and clinicians, we too must guard against hubris.Hopefully our colleagues will help us with that.JRMS should be applauded for exploring the issue.
Standardisation of lung function testing: the authors' replies to readers' comments
Authors: M. R. Miller, J. Hankinson, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, P. Enright, C. van der Grinten, P. Gustafsson, R. Jensen, N. MacIntyre, R. T. McKay, O. F. Pedersen, R. Pellegrino, G. Viegi, J. Wanger
Journal: European Respiratory Journal (2010)

<h3>Objective</h3> Sjogren9s Syndrome (SS) has significant impact on health-related quality of life (HRQL). We sought to evaluate how the Patient Reported Outcome Measurement Information System (PROMIS) domains in SS may supplement the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI). <h3>Methods</h3> A cross-sectional evaluation was performed on consecutive adult patients during visits to a Sjogren9s clinic between March 2018-February 2020. Each patient completed PROMIS short forms related to HRQL, the ESSPRI, and had a clinical assessment. Patients were either classified as SS by 2016 ACR/EULAR criteria or "sicca not otherwise specified (NOS)" and used as a comparison group. Uni- and multivariable linear regression (MVR) models were used to evaluate predictors of PROMIS fatigue, pain interference (PI), and social participation (SP). <h3>Results</h3> 227 SS and 85 patients with sicca NOS were included and did not differ in ESSPRI domains; 26% of the SS and 20% of the sicca NOS group had concurrent autoimmune disease. In SS, PROMIS PI, fatigue, and physical function were at least ½ SD worse than US population normative values. PROMIS PI (r=0.72) and fatigue (r=0.80) highly correlated with ESSPRI pain and fatigue sub-domains. Fatigue and PI, but not dryness or mood disturbance, were the strongest predictors of SP in MVR. <h3>Conclusion</h3> In our SS cohort, PROMIS instruments identified a high disease burden of PI, fatigue, and physical function. Fatigue strongly predicted SP. PROMIS PI and fatigue scores correlated highly with respective ESSPRI domains. PROMIS instruments should be considered to identify relevant HQRL patterns in SS.
PPARγ but not PPARα Ligands Are Potent Repressors of Major Histocompatibility Complex Class II Induction in Atheroma-Associated Cells
Authors: Brenda R. Kwak, Samir Myit, Flore Mulhaupt, Niels Veillard, Nathalie Rufer, Eddy Roosnek, François Mach
Journal: Circulation Research (2002)

Peroxisome proliferator-activated receptors (PPARs) are essential in glucose and lipid metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as diabetes and dyslipidemia. Conversely, antidiabetic glitazones and hypolipidemic fibrate drugs, known as PPARγ and PPARα ligands, respectively, reduce the process of atherosclerotic lesion formation, which involves chronic immunoinflammatory processes. Major histocompatibility complex class II (MHC-II) molecules, expressed on the surface of specialized cells, are directly involved in the activation of T lymphocytes and in the control of the immune response. Interestingly, expression of MHC-II has recently been observed in atherosclerotic plaques, and it can be induced by the proinflammatory cytokine interferon-γ (IFN-γ) in vascular cells. To explore a possible role for PPAR ligands in the regulation of the immune response, we investigated whether PPAR activation affects MHC-II expression in atheroma-associated cells. In the present study, we demonstrate that PPARγ but not PPARα ligands act as inhibitors of IFN-γ–induced MHC-II expression and thus as repressors of MHC-II–mediated T-cell activation. All different types of PPARγ ligands tested inhibit MHC-II. This effect of PPARγ ligands is due to a specific inhibition of promoter IV of CIITA and does not concern constitutive expression of MHC-II. Thus, the beneficial effects of antidiabetic PPARγ activators on atherosclerotic plaque development may be partly explained by their repression of MHC-II expression and subsequent inhibition of T-lymphocyte activation.
Endocrine Treatment of Cancer
Authors: Tim Gulliford, Richard J Epstein
Journal: Journal of the Royal Society of Medicine (1996)

Cancer has been treated by hormonal manipulation for over 100 years. Although therapeutic progress during this period has resulted mainly from clinical observation, more rational treatment approaches are now emerging from insights into the molecular basis of hormone-responsiveness. Among these are the recognition that hormonal signalling effects are transduced via specific receptor proteins, and the possibility that tumour lysis by hormonal therapies is effected by triggering of a programmed cell death pathway. Clinical progress has already been achieved through basic advances: receptor assays, for example, now permit prediction of treatment benefit in various settings. However, much remains to be learned about the mechanism and application of hormonal anticancer treatments.
A New Scoring System to Determine Thromboembolic Risk After Heart Valve Replacement
Authors: Eric G. Butchart, Adrian Ionescu, Nicola Payne, John Giddings, Gary L. Grunkemeier, Alan G. Fraser
Journal: Circulation (2003)

Objective— To determine the most important inflammatory and hematologic predictors of thromboembolism (TE) in patients undergoing valve replacement (VR) to be used in conjunction with clinical risk factors for preoperative risk profiling. Methods and Results— Preoperative and immediately postoperative clinical, echocardiographic, hematologic, biochemical and microbiological parameters were examined prospectively in 370 patients undergoing VR (249 AVR, 93 MVR, 28 DVR). Mean follow-up was 4.4 years (max 6.6 years; total 1566 pt/yrs), and 96 TE events were documented (28 major and 68 minor). INR data were collected on all patients. Laboratory values were considered elevated if they exceeded the 80 th percentile of those of 70 controls with the same distribution of age and gender. IgA antibody to Chlamydia pneumoniae (CP)≥1:64 was considered indicative of significant infection. Predictors of TE on multivariate analysis following AVR were (hazard ratios): CP infection (2.6), previous TE (2.5), raised eosinophils (2.4), cancer history (2.1), postoperative infection (2.0), hypertension (2.0), CABG × 3/4 (2.0), and diabetes (1.9). Predictors of TE following MVR/DVR were raised mean platelet volume (4.0), raised factor VII (3.1), CP infection (2.7), previous mitral valvotomy (2.5), raised fibrinogen (2.2), and raised reticulocytes (2.0). These risk factors were additive when present in the same patient, enabling a scoring system to be developed that accurately predicted risk of TE based on number of risk factors. Conclusions— Selected blood tests and clinical risk factors provide a scoring system that accurately predicts TE risk and may guide prosthesis choice and antithrombotic management.
Sport science and medicine in tennis
Authors: Babette M Pluim, Stuart Miller, David Dines, Per A H F Renström, Gary Windler, Bill Norris, Kathleen Ann Stroia, Amber Donaldson, Kathy Martin
Journal: British Journal of Sports Medicine (2007)

administering medicines to children N comprehensive guidance covering neonates to adolescents For more information please go to bnfc.
Impact of a Children's Health Insurance Program on Newly Enrolled Children
Authors: Judith R. Lave
Journal: JAMA (1998)

Context.-Although there is considerable interest in decreasing the number of US children who do not have health insurance, there is little information on the effect that health insurance has on children and their families.Objective.-Todetermine the impact of children's health insurance programs on access to health care and on other aspects of the lives of the children and their families.Design.-A before-after design with a control group.The families of newly enrolled children were interviewed by telephone using an identical survey instrument at baseline, at 6 months, and at 12 months after enrollment into the program.A second group of families of newly enrolled children were interviewed 12 months after the initial interviews to form a comparison sample.Setting.-The 29 counties of western Pennsylvania, an area with a population of 4.1 million people.Subjects.-Atotal of 887 families of newly enrolled children were randomly selected to be interviewed; 88.3% agreed to participate.Of these, 659 (84%) responded to all 3 interviews.The study population consists of 1031 newly enrolled children.The children were further classified into those who were continuously enrolled in the programs.The 330 comparison families had 460 newly enrolled children.Main Outcome Measures.-Thefollowing access measures were examined: whether the child had a usual source of medical or dental care; the number of physician visits, emergency department visits, and dentist visits; and whether the child had experienced unmet need, delayed care, or both for 6 types of care.Other indicators were restrictions on the child's usual activities and the impact of being insured or uninsured on the families.Results.-Access to health care services after enrollment in the program improved: at 12 months after enrollment, 99% of the children had a regular source of medical care, and 85% had a regular dentist, up from 89% and 60%, respectively, at baseline.The proportion of children reporting any unmet need or delayed care in the past 6 months decreased from 57% at baseline to 16% at 12 months.The proportion of children seeing a physician increased from 59% to 64%, while the proportion visiting an emergency department decreased from 22% to 17%.Since the comparison children were similar to the newly enrolled children at enrollment into the insurance programs, these findings can be attributed to the program.Restrictions on childhood activities because of lack of health insurance were eliminated.Parents reported that having health insurance reduced the amount of family stress, enabled children to get the care they needed, and eased family burdens.Conclusions.-Extendinghealth insurance to uninsured children had a major positive impact on children and their families.In western Pennsylvania, health insurance did not lead to excessive utilization but to more appropriate utilization.
Modeling Defibrillation of the Heart: Approaches and Insights
Authors: Natalia Trayanova, Jason Constantino, Takashi Ashihara, Gernot Plank
Journal: IEEE Reviews in Biomedical Engineering (2011)

Cardiac defibrillation, as accomplished nowadays by automatic, implantable devices (ICDs), constitutes the most important means of combating sudden cardiac death. While ICD therapy has proved to be efficient and reliable, defibrillation is a traumatic experience. Thus, research on defibrillation mechanisms, particularly aimed at lowering defibrillation voltage, remains an important topic. Advancing our understanding towards a full appreciation of the mechanisms by which a shock interacts with the heart is the most promising approach to achieve this goal. The aim of this paper is to assess the current state-of-the-art in ventricular defibrillation modeling, focusing on both numerical modeling approaches and major insights that have been obtained using defibrillation models, primarily those of realistic ventricular geometry. The paper showcases the contributions that modeling and simulation have made to our understanding of the defibrillation process. The review thus provides an example of biophysically based computational modeling of the heart (i.e., cardiac defibrillation) that has advanced the understanding of cardiac electrophysiological interaction at the organ level and has the potential to contribute to the betterment of the clinical practice of defibrillation.