tbuckley/cabot-search huggingface dataset:
Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial
Authors: Edward Chow, Yvette M van der Linden, Daniel Roos, William F Hartsell, Peter Hoskin, Jackson S Y Wu, Michael D Brundage, Abdenour Nabid, Caroline J A Tissing-Tan, Bing Oei, Scott Babington, William F Demas, Carolyn F Wilson, Ralph M Meyer, Bingshu E Chen, Rebecca K S Wong
Journal: The Lancet Oncology (2013)
Endotoxin levels in homes and classrooms of Dutch school children and respiratory health
Authors: José H. Jacobs, Esmeralda J.M. Krop, Siegfried de Wind, Jack Spithoven, Dick J.J. Heederik
Journal: European Respiratory Journal (2012)

Several studies describe indoor pollutant exposure in homes and to a lesser extent in schools. Population studies that include both environments are sparse. This study aims to assess endotoxin levels in primary schools and homes of children. Endotoxin was also studied in relation to asthma and sensitisation. 10 schools with (index) and without (reference) dampness were selected, based on reports and inspections. Cases and controls were selected from 169 homes based on the presence or absence of asthma-like symptoms of children. Classroom and bedroom airborne settled dust was sampled using electrostatic dust fall collectors. Average endotoxin levels in schools ranged from 2178 to 6914 endotoxin units (EU)·m −2 per week compared with 462–1285 EU·m −2 per week in homes. After mutual adjustment for home and school endotoxin, school endotoxin was positively associated with nonatopic asthma (OR 1.11, 95% CI 0.97–1.27), while no associations with endotoxin were found at home. The high endotoxin levels in schools compared with homes indicate that exposure at school can contribute considerably to environmental endotoxin exposure of children and teachers. Our results also suggest that endotoxin in schools may be associated with nonatopic asthmatic symptoms in pupils, although the results require reproduction because of the modest sample size.
STUDIES CONCERNING THE SITE OF RENIN FORMATION IN THE KIDNEY
Authors: Meyer Friedman, Alex Kaplan
Journal: The Journal of Experimental Medicine (1943)

1. The administration of tartrate to adult rabbits was found to produce in some of them, a profound and widespread necrosis of the proximal convoluted tubular epithelium without affecting the other portions of the nephrons. 2. The markedly damaged kidneys were found to be almost completely devoid of pressor substance (renin), indicating that in the mammalian kidney, the epithelium of the proximal convoluted tubules is concerned in the formation or storage of renin.
Role of Survivin in EGFR Inhibitor–Induced Apoptosis in Non–Small Cell Lung Cancers Positive for <i>EGFR</i> Mutations
Authors: Kunio Okamoto, Isamu Okamoto, Wataru Okamoto, Kaoru Tanaka, Ken Takezawa, Kiyoko Kuwata, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Cancer Research (2010)

Abstract The molecular mechanism by which epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKI) induce apoptosis in non–small cell-lung cancer (NSCLC) cells that are positive for activating mutations of the EGFR remains unclear. In this study, we report the effects of the EGFR-TKI gefitinib on expression of the antiapoptotic protein survivin that have functional consequences in EGFR mutation–positive NSCLC cells. Immunoblot analysis revealed that gefitinib downregulated survivin expression, likely through inhibition of the PI3K-AKT signaling pathway, in NSCLC cells positive for EGFR mutation. Stable overexpression of survivin attenuated gefitinib-induced apoptosis and also inhibited the antitumor effect of gefitinib in human tumor xenografts. Furthermore, the combination of survivin overexpression with inhibition of the gefitinib-induced upregulation of the proapoptotic protein BIM attenuated gefitinib-induced apoptosis to a greater extent than either approach alone. Our results indicate that downregulation of survivin plays a pivotal role in gefitinib-induced apoptosis in EGFR mutation–positive NSCLC cells. Furthermore, they suggest that simultaneous interruption of the PI3K-AKT-survivin and MEK-ERK-BIM signaling pathways is responsible for EGFR-TKI–induced apoptotic death in these cells. Cancer Res; 70(24); 10402–10. ©2010 AACR.
Low dose prednisolone or oestrogen in the treatment of women with late onset or persistent acne vulgaris
Authors: C.R. DARLEY, J.W. MOORE, G.M. BESSER, D.D. MUNRO, J.D. KIRBY
Journal: British Journal of Dermatology (1983)

Women with persistent or late onset acne vulgaris were divided into two treatment groups. The first received continuous low dose prednisolone to suppress ACTH-dependent androgen secretion and the second was treated with cyclical oestrogens with medroxyprogesterone to elevate sex hormone binding globulin (SHBG). In both groups there was a significant improvement in the severity of the acne after 4 months' treatment. Although pre-existing hormonal abnormalities were corrected, the improvement in the acne did not correlate with the baseline hormone levels. However, suitable oestrogen-progesterone combinations or low dose prednisolone may be given, alone or in combination, to suppress free circulating androgens in these patients with a high probability of improving their acne.
Inability of chronic chemical sympathectomy to induce coronary collateral growth or development: studies in the rat heart in vivo
Authors: M. P MAXWELL, D. J HEARSE, D. M YELLON, J. M DOWNEY
Journal: Cardiovascular Research (1989)

The influence of chronic chemical sympathectomy on the extent of coronary collateral flow delivered to a zone of regional ischaemia following an acute coronary artery occlusion was examined in the rat. Male rats were randomly assigned to either 6-hydroxydopamine treated or vehicle treated groups (n = 20 in each group). Drug treated animals were injected with 6-hydroxydopamine intravenously as follows: day 1, 10 mg.kg-1; day 2, 50 mg.kg-1; days 7, 8, 14, 15, 21, 28, 35 and 42, 100 mg.kg-1. Control animals were injected in a similar manner with vehicle solution. On day 43, animals were anaesthetised, and their hearts were excised and perfused in the Langendorff mode at a perfusion pressure of 10 kPa. After 5 min the left main coronary artery was ligated and after a further 5 min, 153Gd labelled microspheres (10 microCi, 15 microns diameter) were infused via a side arm on the aortic cannula. This was followed within 3 min by the infusion of 3H-desmethylimipramine (5 microCi) via the same route. Disulphine blue dye was injected via the side arm within 1 min of the desmethylimipramine injection so as to delineate the perfused from the ischaemic region. The hearts were frozen in liquid nitrogen and freeze dried. The dried hearts were separated into ischaemic and non-ischaemic tissue on the basis of the blue dye coloration. The weighed samples were assessed for gamma and beta activity and the ratio of radioactive counts.g-1 in the ischaemic tissue to that of the non-ischaemic tissue was taken as an index of relative coronary collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Reduced Positive Selection in Vector-Borne RNA Viruses
Authors: Christopher H. Woelk, Edward C. Holmes
Journal: Molecular Biology and Evolution (2002)

RNA viruses evolve at greatly elevated rates compared with their DNA counterparts. This is principally due to the high mutation rate associated with RNA polymerase, which introduces approximately one error per genome during each round of viral replication, a rate some two orders of magnitude higher than observed in DNA viruses (Drake et al. 1998). The potential for rapid evolutionary change is thought to provide RNA viruses with unparalleled adaptability (Domingo and Holland 1997), so that a solution can quickly be found to any evolutionary problem, such as those posed by antiviral therapy. Conversely, studies of long-term rates of nucleotide substitution suggest that certain aspects of viral biology, particularly transmission mode, may impose constraints on RNA virus evolution. In particular, reduced rates of nonsynonymous substitution have been recorded in some RNA viruses transmitted by arthropod vectors (Jenkins et al. 2002), suggesting that the requirement to replicate in disparate hosts, like mammals and invertebrates, imposes greater selective constraints than on viruses that only infect phylogenetically similar species (Scott, Weaver, and Mallampalli 1994; Weaver et al. 1999). However, this theory remains controversial, as reiterated by experimental studies of vesicular stomatitis virus (VSV) in cell culture which showed that alternate replication in insect and mammalian cells did not reduce the rate at which mutations appeared or limit fitness increases (Novella et al. 1999). To determine whether vector-borne RNA viruses evolve in the same manner as viruses transmitted by other routes (including blood-borne, fecal-oral, respiratory, sexual, and vertical), and to investigate the nature of selection in viruses in general, we analyzed selection pressures in a wide variety of viruses that infect human populations. The sequences of surface structural (envelope glycoprotein or outer capsid) and internal structural (core capsid or nucleoprotein) genes were collected from all human-associated viruses available on GenBank or the Los Alamos National Laboratory in the case of the human immunodeficiency virus type 1 (HIV-1) (http:// www.hiv.lanl.gov). In the case of the surface genes, sufficiently large intraspecific data sets were available from 45 viruses (18 vector-borne, 27 nonvector-borne). Of
PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts
Authors: David G Molleví, Alvaro Aytes, Mireia Berdiel, Laura Padullés, Maria Martínez-Iniesta, Xavier Sanjuan, Ramon Salazar, Alberto Villanueva
Journal: Molecular Cancer (2009)

We isolate and culture carcinoma-associated fibroblasts (CAFs) from primary tumour (CAFpt), CAFs from corresponding synchronous liver metastasis (CAFlm) as well as normal colonic fibroblasts (NCF) from the same patient. From these cultures, conditioned media (CM) was obtained. Culture of a wide panel of colorectal and pancreatic cell lines in CM from CAFlm resulted in overexpression of mRNA PRL-3 and higher overexpression in CAFs than in non-activated fibroblasts. Moreover PRL-3 mRNA expression correlates with expression of alpha-SMA and deposition of collagen fibrils in the stroma. We demonstrate that products secreted by CAFs trigger PRL-3 overexpression in cancer cells. Identification of these factors may contribute to new stroma-targeted therapies for desmoplastic tumours.
Ethical Philanthropy in Academic Psychiatry
Authors: Laura Weiss Roberts
Journal: American Journal of Psychiatry (2006)

From an ethical perspective, psychiatrists cannot accept gifts of significant monetary value from their patients. This guideline raises important questions regarding institutional practices related to gift-giving in academic psychiatry. The first aim of this article is to explain the ethical tensions and shared ethical commitments of the professions of psychiatry and philanthropy. The second aim is to outline a series of steps that may be undertaken to assure ethical philanthropic practices within an institution, including the establishment of a committed advisory workgroup and the creation of ground rules and safeguards for gift-giving. Each situation should be evaluated for "ethical risk," and specific measures to safeguard donors should be considered.The author outlines methods to manage, minimize, or eliminate conflict of interest issues, including identification and disclosure of conflicting interests, role separation, goal clarification, confidentiality protections, proper timing, and ongoing oversight. Three case illustrations are provided and discussed.The process of institutional engagement, dialogue, and shared problem-solving is especially important. A shared, constructive ethic will be attained only if leaders and diverse stakeholders communicate the value of the new approach through their words, expectations, and actions.Through these efforts, greater attention will be given to the concerns of people with mental illness, and academic institutions may be better able to fulfill their responsibilities to this important but neglected population now and in the future.
Who misses the second step of evaluation in tuberculosis contact screening?
Authors: F. Soares Pires, C. Pinto, R. Duarte
Journal: European Respiratory Journal (2011)

called multiple-trigger) wheeze are indeed distinct disease entities [3][4][5]10].However, a clear limitation of the study is the fact that the results are based on parental report of triggers.Replication of the study or the analysis using alternative methods of documentation would be beneficial.Our findings provide support for an old concept proposing that infection and allergy can cause airway narrowing in susceptible individuals, either by acting directly (as trigger factors) or by induction of bronchial hyperresponsiveness (as inducing factors).Exercise, in contrast, is merely a trigger, which leads to airway narrowing only in the presence of bronchial hyperresponsiveness caused by other factors (fig.1).Finally and most importantly, our observation that there was no evidence of dependence between viral and allergic triggers suggests that the mechanisms underlying allergen-and infection-related wheeze might be independent.This supports the notion that exclusive viral wheeze and allergic wheeze are distinct phenotypes which differ in their aetiology [10].This work should lead to further metabolomic and physiological studies in order to confirm the characteristics of different phenotypes of wheezing disease in young children.
Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer
Authors: H G. Welch
Journal: BMJ (2002)

Few stories in medicine are as sobering as the American experience with autologous bone marrow transplantation (ABMT) for treating breast cancer. It is a story of young women dying from aggressive disease, well meaning physicians trying to be equally aggressive in treating it, and lawyers arguing that insurers should pay the bill. It is also a story of professional interests, weak research, financial gain, politics, and fraud. Because of its potential relevance to complex cancer therapies currently in development (such as gene therapy) we recount here the story and its lessons.

#### Summary points

For over 10 years bone marrow transplantation for breast cancer was seen as an example of the general dilemma about who should pay for costly new life saving therapies

This characterisation obscured the more basic question: Did it work?

Intermediate outcomes and inadequate controls made preliminary evidence misleading

Statements by physicians in the literature and the general press reinforced the presumption of benefit, as did the decision of government bodies to mandate insurance coverage

The findings of major randomised trials did not support the use of the therapy

This experience provides lessons relevant to complex cancer therapies currently in development

Bone marrow transplantation was first performed to treat primary bone marrow disorders, but in the late 1970s it started to be used also for “rescuing” patients (using their own marrow) after supralethal chemotherapy or radiation for solid tumours.1 By the mid-1980s there were strong proponents for using it this way in advanced breast cancer—on the basis that higher chemotherapy doses would be expected to kill more tumour cells. The enthusiasm for this hypothesis was evident in comments made to the New York Times in 1989 by the head of the breast cancer section at the National Cancer Institute: “The evidence is absolutely convincing that the dose intensity is …
CD14 Tobacco Gene–Environment Interaction Modifies Asthma Severity and Immunoglobulin E Levels in Latinos with Asthma
Authors: Shweta Choudhry, Pedro C. Avila, Sylvette Nazario, Ngim Ung, Jennifer Kho, Jose R. Rodriguez-Santana, Jesus Casal, Hui-Ju Tsai, Alfonso Torres, Elad Ziv, Monica Toscano, Jody Senter Sylvia, MariaElena Alioto, Michael Salazar, Ivan Gomez, Joanne K. Fagan, Jorge Salas, Craig Lilly, Henry Matallana, Richard A. Castro, Moises Selman, Scott T. Weiss, Jean G. Ford, Jeffrey M. Drazen, William Rodriguez-Cintron, Rocio Chapela, Edwin K. Silverman, Esteban González Burchard
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14.To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families.We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1 using both family-based (p = 0.0009) and cross-sectional cohort (p = 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity.Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma.
A white thing
Authors: J. van Brake
Journal: Behavioral and Brain Sciences (1998)

I have no problem with Millikan's saying that Mama, milk, and mouse are substances, but I do not see why this list cannot be extended with white, red cows, things, vovetas, lhenxa, GRUE, and so on. In the right circumstances, given the right training, the characteristics of substances that Millikan provides work equally well for each of them.
Biological and clinical implications of retinoic acid-responsive genes in human hepatocellular carcinoma cells
Authors: Keita Kanki, Yuji Akechi, Chisa Ueda, Hiroyuki Tsuchiya, Hiroki Shimizu, Naoki Ishijima, Kan Toriguchi, Etsuro Hatano, Kanenori Endo, Yasuaki Hirooka, Goshi Shiota
Journal: Journal of Hepatology (2013)
Development of phenotype algorithms using electronic medical records and incorporating natural language processing
Authors: K. P. Liao, T. Cai, G. K. Savova, S. N. Murphy, E. W. Karlson, A. N. Ananthakrishnan, V. S. Gainer, S. Y. Shaw, Z. Xia, P. Szolovits, S. Churchill, I. Kohane
Journal: BMJ (2015)

Electronic medical records are emerging as a major source of data for clinical and translational research studies, although phenotypes of interest need to be accurately defined first. This article provides an overview of how to develop a phenotype algorithm from electronic medical records, incorporating modern informatics and biostatistics methods.
Nodal upstaging after thoracoscopic versus open lobectomy
Authors: Ulrik Sartipy
Journal: Thorax (2013)

Nodal upstaging after thoracoscopic versus open lobectomyIn this nationwide database study from Denmark, nodal upstaging and survival after thoracoscopic and open lobectomy for clinical stage I non-small cell lung cancer (NSCLC) was investigated.Clinical data for all patients diagnosed with lung cancer in Denmark are obligatorily reported to the national Danish Lung Cancer Registry (DLCR).Cross-linkage with the DLCR and other national registers is used to validate completeness of data and survival status is obtained from the Centralised Civil Registry.Surgery for lung cancer in Denmark is only performed by thoracic surgeons at four university hospitals.The DLCR was used to identify 1513 patients who underwent lobectomy for clinical stage I NSCLC between 2007 and 2011.Thoracoscopic lobectomy was performed in 47% and thoracotomy was used in 53%.The use of a minimally invasive approach increased gradually during the study period.Information regarding sex, age, Charlson comorbidity index, use of positron-emission tomography, the preoperative staging method, clinical TNM (cTNM), surgical approach (thoracoscopic or open), lobe resected, number of lymph node stations harvested, pathological TNM ( pTNM), final histology, and survival time was collected from the DLCR.Nodal upstaging (the discovery of lymph node metastases in the surgical samples of patients clinically staged to be node negative) was identified by comparing cTNM with pTNM and occurred in 281 patients (18.6%) and was significantly more frequent after thoracotomy (24.6% vs 11.9%; p<0.001).Although crude estimates of survival during a median follow-up of 28 months favoured a less invasive procedure, the adjusted survival showed no difference between thoracoscopic and open surgery (HR 0.98; 95% CI 0.80 to 1.22).By design, the study was limited by selection bias due to the non-randomised treatment allocation, that is, the operative approach was at the discretion of the surgeon, and the reason for selecting either thoracoscopic or open lobectomy was not recorded in the register.Moreover, neither the rate nor the reason for intraoperative conversion from thoracoscopic to open procedure was available from the DLCR.Previous studies have questioned the efficacy of the surgical lymph node evaluation during minimally invasive lobectomies for NSCLC.Node evaluation is important because the findings may affect the decision for adjuvant chemotherapy.Nodal upstaging was more common after open lobectomy in this study, although survival was similar between treatment groups.
Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure
Authors: Stefano Ghio, Antonello Gavazzi, Carlo Campana, Corinna Inserra, Catherine Klersy, Roberta Sebastiani, Eloisa Arbustini, Franco Recusani, Luigi Tavazzi
Journal: Journal of the American College of Cardiology (2001)