tbuckley/cabot-search huggingface dataset:
Cigarettes and drugs in Northern Ireland
Authors: J. Robshaw
Journal: BMJ (1996)

Telling patients there is nothing wrong Randomised controlled trials are needed EDrroR,-It is still unclear from the literature whether investigative tests reassure patients with anxieties about the presence of serious disease.' 2 Ray Fitzpatrick discusses some of the possible reasons for this, including psychiatric morbidity, poor communication, and the "wild card effects" mentioned in the study by I G McDonald and colleagues.3Other psychological processes in patients are
Abstract 16824: Fully Validated Mri-Based Computational Models of Swine Hearts With Post-Infarction Ventricular Tachycardia
Authors: Dongdong Deng, Hermenegild Arevalo, Henry Halperin, Natalia Trayanova
Journal: Circulation (2014)

Background:  Identification of the optimal ablation sites in hearts with infarct related ventricular tachycardia (VT) remains difficult to achieve with the current catheter based mapping techniques. Limitations arise for ambiguities in determining the location(s) of reentrant pathways arising from the infarct zone. The goal of this study was to develop fully validated, individualized computer models of infarcted swine hearts that can be used to predict the characteristics of infarct related VT and where it is localized, and thus the optimal targets of ablation.   Methods:  In 5 pigs 10 weeks post infarction, VT was induced via programmed electrical stimulation. Epicardial sock electrodes were used to record electrical activity. The heart was then explanted and imaged using contrast enhanced MRI. The images were segmented to identify myocardium, semi viable gray zone (GZ), and scar based on pixel intensity. GZ was modeled as a region with longer APD and increased anisotropy, and scar as passive tissue. VT induction was simulated in the models following the experimental protocol.   Results:  All 5 pigs were inducible for VT with mean cycle length of 186±30 ms. In 3 pigs VT manifested as centrifugal activity; the other 2 pigs had epicardial reentry (Fig top row). Models were successfully constructed from MRI (2 nd  row). The models were inducible for VTs with morphologies and cycle lengths (187±33 ms) that matched well with the experiment (3 rd  row). Simulations also revealed that in the cases of centrifugal activity, the underlying VT reentrant circuits were located intramurally within the ventricular wall where they were not detectable from surface recordings alone (Fig A 4 th  row).   Conclusions:  These results demonstrate that MRI-based computer models of hearts with myocardial infarction provide a unique opportunity to predict and analyze VT resulting for from specific infarct zone architecture, and thus may assist clinicians in identifying and ablating the reentrant circuit(s).
Abstract 11255: Collagelin Analogs Target Collagen and Identify Myocardial Fibrosis
Authors: Cynthia A Davies-Venn, Sung-Jin Lee, Insook Kim, Heejung Kim, Zhengsheng Yao, Craig A Emter, Chang H Paik, David A Bluemke
Journal: Circulation (2014)

Introduction:  Myocardial fibrosis is a common adverse condition associated with heart failure and remodeling. At present, there is a need for molecular imaging methods to detect fibrosis.   Hypothesis:  Analogs of collagelin (a 22 amino acid peptide mimetic of glycoprotein GPVI), named CRPA monomer and collagelin dimer, provide specific molecular binding to collagen in cardiac fibrosis.   Methods:  Collagelin analog binding was tested by Blitz interferometry analysis, ELISA on a collagen coated well plate using luminescence detection, Cu64-CRPA autoradiography and staining of myocardial tissues with suspected fibrosis. Tissue samples were obtained from MI rats (n=15); swine with heart failure (n=15), either untreated or treated with enzyme inhibitors Saxagliptin or Tadalafil; as well as human MI tissue. In ex-vivo binding assays, 8μm sections were stained with biotin-CRPA, followed by streptavidin-horseradish peroxidase and visualized by DAB stain. Percent fibrosis was validated by picrosirius red and analyzed by ImageJ.   Results:  Blitz analysis was used to assess association and dissociation curves for CRPA and collagelin dimer binding to collagen. By ELISA, a concentration dependent increase in luminescence showed CRPA consistently bound collagen. A blocking study with excess unlabeled CRPA showed a decrease in biotin-CRPA binding, suggesting peptide specificity. Autoradiography and biotin-CRPA histology of rats 5 weeks post infarct identified 15-20% fibrosis at the edge of the myocardial tissue. In swine, untreated controls showed fiber disarray and increased CRPA and picrosirius red staining, while drug treated groups showed minimal staining. CRPA also showed specificity to infarcted tissue from human myocardium and picrosirius red confirmed location of fibrosis.   Conclusion:  CRPA monomer and collagelin dimer bind myocardial fibrosis. Collagelin analogs have potential utility as molecular probes for identifying myocardial fibrosis.
COPD in women: susceptibility or vulnerability?
Authors: Raúl H. Sansores, Alejandra Ramírez-Venegas
Journal: European Respiratory Journal (2015)

The concepts of susceptibility and vulnerability are intertwined because vulnerability is sometimes a consequence of being susceptible. Women are more likely to be susceptible to chronic obstructive pulmonary disease (COPD) than men [1]. As many women continue to smoke during pregnancy, the impact of tobacco in women can begin before birth [2], because maternal smoking during pregnancy may increase the risk of childhood respiratory diseases [3] and reduce lung function [2]. Indeed, this susceptibility starts before women become smokers. For example, women with specific genotype variants are at a significantly increased risk of becoming heavy smokers [4], while those women with the haplotype TAS2R38 (proline-alanine-valine) have a genetic propensity to experience heightened bitter taste perception and an increased preference for menthol cigarettes [5]. Recent findings of the Global Youth Tobacco survey on adolescents aged 13–15 years showed that young girls smoke as much as young boys [6]. The early onset of smoking may have a greater deleterious impact on lung function among girls [7] because their lungs are smaller than those of males. Accordingly, the same exposure to a given number of cigarettes smoked can lead to more deleterious effects in women [8]. In this regard, once young females become smokers, addiction may be reinforced by both nicotine and the sensory and social contexts of smoking. Motivations associated with gender can provoke women to have different cues for smoking compared with males [9]; therefore, women are more vulnerable to the social context of smoking and can easily become involved in the nicotine addictive process, along with consequent disease risks. Women are both more susceptible and more vulnerable than men when it comes to COPD <http://ow.ly/UhMQ3>
Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci
Authors: Eilis Hannon, Helen Spiers, Joana Viana, Ruth Pidsley, Joe Burrage, Therese M Murphy, Claire Troakes, Gustavo Turecki, Michael C O'Donovan, Leonard C Schalkwyk, Nicholas J Bray, Jonathan Mill
Journal: Nature Neuroscience (2015)
Successful treatment with an anti-PD-1 antibody for progressing brain metastases in renal cell cancer
Authors: C. Rothermundt, C. Hader, S. Gillessen
Journal: Annals of Oncology (2015)

Efficacy of anti-PD-1 antibody was demonstrated in a patient with metastatic renal cell cancer on systemic steroids for progressive and symptomatic brain metastases.
Characterization of chiral tamoxifen analogs
Authors: Brian J. Kennedy, Peter Reczek, Gokul Das, Ralph J. Bernacki, Huw Davies, William Mungall
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1219 

Characterization of Chiral Tamoxifen Analogs Tamoxifen (TAM), a non-steroidal selective estrogen receptor modulator (SERM), is used for the treatment of estrogen receptor (ER) positive breast cancer. There are limitations however to its usefulness including a 4-fold increase of endometrial carcinoma associated with long term usage in postmenopausal women and the development of resistance. Based on these problems we have synthesized and evaluate a series of new chiral tamoxifen analogs. These stereo-selective chiral derivatives differ from TAM by replacement of the central double bond with a cyclopropyl moiety, introducing two chiral centers within the molecule. We hypothesize that novel chiral TAM analogs will demonstrate tissue specific activity through ER isotype (α and β) selectivity as well as inducing unique ligand-ER complex conformations. Our studies aim to direct the syntheses of future chiral TAM analogs by determining what effects altering the size, hydrophobicity and stereochemistry of a molecule have on its interaction with ER isotypes. Once characterized, these analogs are not only potential therapeutic agents, but become tools with which to assess SERM-ER interactions. Growth inhibitory properties were analyzed using MCF7-S (ER+ breast cancer cell line), its sublines TAM resistant MCF7/LCC2, Faslodex resistant MCF7/LCC9 (Brunner et al., Cancer Res. 57:3486, 1997) and the ER- breast cancer cell line BT-20. Cell growth was assessed using the sulforhodamine B colorimetric assay. Analog 99149 was found to be 3-fold more potent than TAM and 99148 (its enantiomer) using MCF7-S, while 02009 was found to be 2-fold more potent than TAM against resistant LCC2 cells. Isolated ER competitive binding data correlates ERα binding affinity with growth inhibitive activity in MCF7-S cells. Similar experiments performed with ERβ did not correlate with cell growth inhibitory activity. This suggests that ERα plays a vital role in SERM growth inhibitory activity in MCF7-S cells. Reporter plasmid XETL containing an estrogen response element (ERE) linked to a luciferase gene, enabled the evaluation of direct inhibition of ERE mediated gene expression. MCF7-S cells were transiently transfected with XETL and treated with 100nM of E2 and/or 2μM of TAM or analogs. Agent 99149 was found to be less potent than TAM in inhibiting ERE mediated transcription. This does not directly correlate with the growth inhibitory effects suggesting that the greater antiproliferative activity seen with 99149 may be due to drug effects other than inhibition of ERE gene expression. Structure-function relationships are being analyzed within a set of ten tamoxifen analogs. (This work is supported by NCI Student Training Grant CA09072-28)
Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure
Authors: Rajeshwar P. Mookerjee, Marco Pavesi, Karen Louise Thomsen, Gautam Mehta, Jane Macnaughtan, Flemming Bendtsen, Minneke Coenraad, Jan Sperl, Pere Gines, Richard Moreau, Vicente Arroyo, Rajiv Jalan
Journal: Journal of Hepatology (2015)
Antimicrobial susceptibility of stenotrophomonas maltophilia isolated from respiratory specimens from a tertiary care center in Pakistan
Authors: Kauser Jabeen, Joveria Farooqi, Muhammad Irfan, Erum Khan, Rumina Hasan
Journal: European Respiratory Journal (2013)

Stenotrophomonas maltophilia (SM) is an opportunistic pathogen that results in serious infections including pneumonia in hospitalized patients. Management of these infections is difficult due to intrinsic resistance of SM to various antimicrobials. Acquired resistance to first line agents have also been reported with increasing frequency. This study evaluates antimicrobial resistance of SM isolated from respiratory specimens at a tertiary care hospital of Pakistan from 2008-2012.  Methods:  The study was conducted at the Aga Khan University Hospital, Karachi, Pakistan. During the study period SM isolates were identified using standard methodology. SM strains isolated from respiratory specimens (sputum, tracheal aspirates, bronchoalveolar lavage) were included. Duplicate isolates from same patients were excluded. Antimicrobial susceptibilities were determined using disc diffusion and were interpreted according to Clinical Laboratory Standards Institute (CLSI) criteria.  Results: A total of 288 isolates from 288 hospitalized patients were obtained from respiratory specimens during the study period. 13/288 (4.5%) of these patients had concomitant bacteremia. 190 patients were male and 98 patients were females. 4.9% of the isolates were resistant to cotrimoxazole, 39.9% of the isolates were resistant to ceftazidime and 9.6% of the isolates were resistant to ciprofloxacin. Resistance was not observed against colistin.  Conclusion: Due to low resistance, cotrimoxazole remains the first line drug for the management of respiratory tract infections due to SM in our setup. A high resistance to ceftazidime precludes the use of this drug for empirical management.
Association of Epstein-Barr virus antibody levels with precancerous gastric lesions in a high risk cohort
Authors: Charles Rabkin, Wei-cheng You, Evelyne Lennette, Mitchell Gail, Aaron Schetter
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1748 

The ubiquitous Epstein Barr virus (EBV) has been implicated in a variety of cancers and increasing evidence supports a role in gastric cancer. Viral DNA is detectable in 5-15% of gastric tumors from different geographic regions and EBV antibody titers increase prior to diagnosis of EBV-positive tumors. This study evaluated the association between EBV antibody titers and the precancerous gastric lesions: chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). Sera were obtained 3 years after diagnosis of either CAG (n=71) or DYS (n=112) in a cohort study from Linqu, China. Immunoglubulin G antibody titers to EBV nuclear antigen (EBNA) and viral capsid antigen (VCA) were determined by 2-fold serial dilutions using immunofluorescence assays. Histologic progression and regression were assessed by gastroscopic examinations at the time of phlebotomy and at follow-up 2 years later. Odds ratios (OR) for greater than median antibody titers were age- and sex-adjusted by multivariable logistic regression. 19/71 (27%) CAG subjects had worse histology and 64/112 (57%) DYS subjects had improved histology on the first examination; 37 subjects progressed and 34 subjects regressed between the two examinations. Subjects with new or persistent DYS tended to have high (>1:320) anti-EBNA titers, particularly at the 2 year follow-up, with OR 3.3 (p trend not significant) and 4.2 (p trend=.05), respectively. Subjects with histologic progression between examinations tended to have both high anti-EBNA and high (>1:640) anti-VCA titers, particularly among those with IM at phlebotomy, with OR 5.7 (p=.01) and 3.8 (p=.05), respectively. Subjects who regressed between examinations were non-signficantly less likely to have high anti-EBNA and anti-VCA titers. These observations are consistent with a role for EBV reactivation at an early phase of gastric carcinogenesis. Future studies incorporating viral DNA detection could potentially reveal stronger associations with a subset of precancerous gastric lesions, as previously found with EBV-positive gastric cancer.
The current state of introduction of human papillomavirus vaccination into national immunisation schedules in Europe: first results of the VENICE2 2010 survey
Authors: F Dorleans, C Giambi, L Dematte, S Cotter, P Stefanoff, J Mereckiene, D O’Flanagan, P L Lopalco, F D'Ancona, D Lévy-Bruhl, Collective on behalf of the VENICE 2 project gatekeepers group
Journal: Eurosurveillance (2010)

The Venice 2 human papillomavirus vaccination survey evaluates the state of introduction of the HPV vaccination into the national immunisation schedules in the 29 participating countries. As of July 2010, 18 countries have integrated this vaccination. The vaccination policy and achievements vary among those countries regarding target age groups, delivery infrastructures and vaccination coverage reached. Financial constraints remain the major obstacle for the 11 countries who have not yet introduced the vaccination.
Primary care for children in the 21st century [editorial]
Authors: Hall D, Sowden D
Journal: BMJ (2005)

The British model of general practice is rightly admired. Explicit responsibility for a defined population facilitates a public health dimension to health care. The training emphasises teamwork consultation skills management of undifferentiated symptoms and the integration of psychosocial and biological aspects of health and illness in the context of the family and community. These skills are crucial for working with children and young people and the recently published national service framework for children has a whole section on primary care. Therefore to question the future of children’s health care in general practice may seem perverse but there are several causes for concern.  (excerpt)
Treatment failure in case of typhoid fever imported from India to Czech Republic, December 2008 - January 2009
Authors: L Lukáčová, I Orságová, A Zjevíková, E Chmelařová
Journal: Eurosurveillance (2009)

In this report we describe a case of typhoid fever in a Czech patient with history of travel to India and discuss antibiotic treatment failure which led to the relapse of fever.
Evidence of a Christmas spirit network in the brain: functional MRI study
Authors: Anders Hougaard, Ulrich Lindberg, Nanna Arngrim, Henrik B W Larsson, Jes Olesen, Faisal Mohammad Amin, Messoud Ashina, Bryan T Haddock
Journal: BMJ (2015)

To detect and localise the Christmas spirit in the human brain.Single blinded, cross cultural group study with functional magnetic resonance imaging (fMRI).Functional imaging unit and department of clinical physiology, nuclear medicine and PET in Denmark.10 healthy people from the Copenhagen area who routinely celebrate Christmas and 10 healthy people living in the same area who have no Christmas traditions.Brain activation unique to the group with Christmas traditions during visual stimulation with images with a Christmas theme.Functional brain scans optimised for detection of the blood oxygen level dependent (BOLD) response were performed while participants viewed a series of images with Christmas themes interleaved with neutral images having similar characteristics but containing nothing that symbolises Christmas. After scanning, participants answered a questionnaire about their Christmas traditions and the associations they have with Christmas. Brain activation maps from scanning were analysed for Christmas related activation in the "Christmas" and "non-Christmas" groups individually. Subsequently, differences between the two groups were calculated to determine Christmas specific brain activation.Significant clusters of increased BOLD activation in the sensory motor cortex, the premotor and primary motor cortex, and the parietal lobule (inferior and superior) were found in scans of people who celebrate Christmas with positive associations compared with scans in a group having no Christmas traditions and neutral associations. These cerebral areas have been associated with spirituality, somatic senses, and recognition of facial emotion among many other functions.There is a "Christmas spirit network" in the human brain comprising several cortical areas. This network had a significantly higher activation in a people who celebrate Christmas with positive associations as opposed to a people who have no Christmas traditions and neutral associations. Further research is necessary to understand this and other potential holiday circuits in the brain. Although merry and intriguing, these findings should be interpreted with caution.
Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I
Authors: Cristina Martin-Higueras, Sergio Luis-Lima, Eduardo Salido
Journal: Molecular Therapy (2015)

Primary hyperoxaluria type 1 (PH1) is caused by deficient alanine-glyoxylate aminotransferase, the human peroxisomal enzyme that detoxifies glyoxylate. Glycolate is one of the best-known substrates leading to glyoxylate production, via peroxisomal glycolate oxidase (GO). Using genetically modified mice, we herein report GO as a safe and efficient target for substrate reduction therapy (SRT) in PH1. We first generated a GO-deficient mouse (Hao1(-/-)) that presented high urine glycolate levels but no additional phenotype. Next, we produced double KO mice (Agxt1(-/-) Hao1(-/-)) that showed low levels of oxalate excretion compared with hyperoxaluric mice model (Agxt1(-/-)). Previous studies have identified some GO inhibitors, such as 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST). We herein report that CCPST inhibits GO in Agxt1(-/-) hepatocytes and significantly reduces their oxalate production, starting at 25 µM. We also tested the ability of orally administered CCPST to reduce oxalate excretion in Agxt1(-/-) mice, showing that 30-50% reduction in urine oxalate can be achieved. In summary, we present proof-of-concept evidence for SRT in PH1. These encouraging results should be followed by a medicinal chemistry programme that might yield more potent GO inhibitors and eventually could result in a pharmacological treatment for this rare and severe inborn error of metabolism.
Abstract ES5-2: Second primary cancers among breast cancer survivors: Incidence and risk factors
Authors: Christopher I. Li
Journal: Cancer Research (2015)

Abstract Five-year survival after invasive breast cancer is now at 90% and an estimated 2.97 million U.S. women are breast cancer survivors. The high incidence of invasive breast cancer, with over 220,000 U.S. women newly diagnosed every year, coupled with continued advances in survival has resulted in an ever increasing number of women at risk of developing a second primary cancer. Indeed, 41% of all second primary cancers diagnosed among U.S. women occur among breast cancer survivors and approximately 10% of breast cancer survivors will develop a second primary cancer. The four most common sites of second primary cancer, breast, lung, colon and endometrium, account for 70% of these second primaries. The appreciable risk of second primary cancer in breast cancer survivors is well-documented, yet relatively little is known about the etiologic and molecular determinants of these second primaries and little to no information on second primary cancer risk has been incorporated into preventive efforts and clinical care because of this evidence gap. This presentation will provide information on the following: 1. Descriptive epidemiology of second primary cancers among breast cancer survivors, 2. Review of the literature on risk factors for second primary breast cancer, and 3. Briefly describe the limited knowledge regarding risk factors for non-breast second primary breast cancers. Further studies of factors contributing to second primary cancers among breast cancer survivors can 1. Define the relationships between therapies for a first breast cancer and risk of these second cancers; 2. Clarify contributions of patient/clinical factors including modifiable exposures; and 3. Molecular profiling of first primary breast tumors aimed at distinguishing those at high vs. low risk of second primaries could advance approaches to risk stratification, tailored surveillance, treatment choice, and preventive interventions. Citation Format: Christopher I. Li. Second primary cancers among breast cancer survivors: Incidence and risk factors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES5-2.
Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy
Authors: Madhav V. Dhodapkar, Rachael Sexton, Rituparna Das, Kavita M. Dhodapkar, Lin Zhang, Ranjini Sundaram, Sonal Soni, John J. Crowley, Robert Z. Orlowski, Bart Barlogie
Journal: Blood (2015)