tbuckley/cabot-search huggingface dataset:
Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain Injury
Authors: Tong-Min Wang, Guo-Ping Shen, Ming-Yuan Chen, Jiang-Bo Zhang, Ying Sun, Jing He, Wen-Qiong Xue, Xi-Zhao Li, Shao-Yi Huang, Xiao-Hui Zheng, Shao-Dan Zhang, Ye-Zhu Hu, Hai-De Qin, Jin-Xin Bei, Jun Ma, Jianbing Mu, Yin Yao Shugart, Wei-Hua Jia
Journal: JNCI Journal of the National Cancer Institute (2018)

Radiation-induced brain injury is a nonnegligible issue in the management of cancer patients treated by partial or whole brain irradiation. In particular, temporal lobe injury (TLI), a deleterious late complication in nasopharyngeal carcinoma, greatly affects the long-term life quality of these patients. Although genome-wide association studies (GWASs) have successfully identified single nucleotide polymorphisms (SNPs) associated with radiation toxicity, genetic variants contributing to the radiation-induced brain injury have not yet been assessed. We recruited and performed follow-up for a prospective observational cohort, Genetic Architecture of Radiotherapy Toxicity and Prognosis, using magnetic resonance imaging for TLI diagnosis. We conducted genome-wide association analysis in 1082 patients and validated the top associations in two independent cohorts of 1119 and 741 patients, respectively. All statistical tests were two-sided. We identified a promoter variant rs17111237 (A > G, minor allele frequency [MAF] = 0.14) in CEP128 associated with TLI risk (hazard ratio = 1.45, 95% confidence interval = 1.26 to 1.66, Pcombined=3.18 × 10–7) which is in moderate linkage disequilibrium (LD) with rs162171 (MAF = 0.18, R2 = 0.69), the top signal in CEP128 (hazard ratio = 1.46, 95% confidence interval = 1.29–1.66, Pcombined= 6.17 × 10–9). Combining the clinical variables with the top SNP, we divided the patients into different subgroups with varying risk with 5-year TLI-free rates ranging from 33.7% to 95.5%. CEP128, a key component of mother centriole, tightly interacts with multiple radiation-resistant genes and plays an important role in maintaining the functional cilia, which otherwise will lead to a malfunction of the neural network. We found that A > G alteration at rs17111237 impaired the promoter activity of CEP128 and knockdown of CEP128 decreased the clonogenic cell survival of U87 cells under radiation. Noteworthy, 12.7% (27/212) of the GWAS-based associated genes (P < .001) were enriched in the neurogenesis pathway. This three-stage study is the first GWAS of radiation-induced brain injury that implicates the genetic susceptibility gene CEP128 involved in TLI development and provides the novel insight into the underlying mechanisms of radiation-induced brain injury.
Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
Authors: Qingyi Ma, Zhen Zhao, Abhay P Sagare, Yingxi Wu, Min Wang, Nelly Chuqui Owens, Philip B Verghese, Joachim Herz, David M Holtzman, Berislav V Zlokovic
Journal: Molecular Neurodegeneration (2018)

Abstract Background Clearance at the blood-brain barrier (BBB) plays an important role in removal of Alzheimer’s amyloid-β (Aβ) toxin from brain both in humans and animal models. Apolipoprotein E (apoE), the major genetic risk factor for AD, disrupts Aβ clearance at the BBB. The cellular and molecular mechanisms, however, still remain unclear, particularly whether the BBB-associated brain capillary pericytes can contribute to removal of aggregated Aβ from brain capillaries, and whether removal of Aβ aggregates by pericytes requires apoE, and if so, is Aβ clearance on pericytes apoE isoform-specific. Methods We performed immunostaining for Aβ and pericyte biomarkers on brain capillaries (&lt; 6 μm in diameter) on tissue sections derived from AD patients and age-matched controls, and APP Swe/0 mice and littermate controls. Human Cy3-Aβ42 uptake by pericytes was studied on freshly isolated brain slices from control mice, pericyte LRP1-deficient mice ( Lrp lox/lox ;Cspg4-Cre ) and littermate controls. Clearance of aggregated Aβ42 by mouse pericytes was studied on multi-spot glass slides under different experimental conditions including pharmacologic and/or genetic inhibition of the low density lipoprotein receptor related protein 1 (LRP1), an apoE receptor, and/or silencing mouse endogenous Apoe in the presence and absence of human astrocyte-derived lipidated apoE3 or apoE4. Student’s t-test and one-way ANOVA followed by Bonferroni's post-hoc test were used for statistical analysis. Results First, we found that 35% and 60% of brain capillary pericytes accumulate Aβ in AD patients and 8.5-month-old APP Sw/0 mice, respectively, compared to negligible uptake in controls. Cy3-Aβ42 species were abundantly taken up by pericytes on cultured mouse brain slices via LRP1, as shown by both pharmacologic and genetic inhibition of LRP1 in pericytes. Mouse pericytes vigorously cleared aggregated Cy3-Aβ42 from multi-spot glass slides via LRP1, which was inhibited by pharmacologic and/or genetic knockdown of mouse endogenous apoE. Human astrocyte-derived lipidated apoE3, but not apoE4, normalized Aβ42 clearance by mouse pericytes with silenced mouse apoE. Conclusions Our data suggest that BBB-associated pericytes clear Aβ aggregates via an LRP1/apoE isoform-specific mechanism. These data support the role of LRP1/apoE interactions on pericytes as a potential therapeutic target for controlling Aβ clearance in AD.
GW29-e0690 Trimethylamine-N-oxide induces oxidative injure in H9C2 cells through suppression of the AMPK-PGC-1alpha pathway
Authors: Jiaying Li, Qingchun Zeng, Xi Yang, Zuheng Liu, Wenjun Xiong, Tianyu Xu, Qiong Zhan, Yujia Bai, Wenyan Lai, Hao Ren, Dingli Xu
Journal: Journal of the American College of Cardiology (2018)
AB0116 Adipose derived stem cellsuppressed synovial inflammation in skg/jcl mice in vivo and inflammatory cytokine in synovial fibroblast in vitro
Authors: H. Ueyama, T. Okano, K. Orita, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adipose derived stem cell (ADSC) is one of the stem cells produced by adipose tissue which can be collected easily and in large quantities. It has been reported the anti-inflammatory effect of ADSC in some disease models.<sup>1</sup> However, the effect of ADSC for synovitis such as rheumatoid arthritis (RA) is unknown. <h3>Objectives</h3> The aim of this study is to investigate the effects of ADSC for joint synovitis and cartilage degeneration in SKG/Jcl mice <i>in vivo</i> and the effects of ADSC for synovial fibroblast <i>in vitro</i>. <h3>Methods</h3> SKG/Jcl mice which developed auto-immune arthritis by adjuvant stimulation were used as RA animal model.<sup>2</sup><i>In vivo</i>, the intra-articular injections of ADSC (ADSC group; n=10) or PBS (PBS group, n=10) were performed to the bilateral knee of SKG mice with arthritis. The knee joint was histologically assessed with synovitis score and Mankin score at 2 weeks after ADSC injection. <i>In vitro</i>, the anti-inflammatory effect of ADSC for stimulated human synovial fibroblast was analysed by real-time RT-PCR. <h3>Results</h3> <i>In vivo</i>, the synovitis score and Mankin score were statistically lower in ADSC group (synovitis score 2.0±0.7 vs 6.0±1.6, p&lt;0.01 and Mankin score 2.2±0.8 vs 4.9±0.8, p&lt;0.01) (figure 1). <i>In vitro</i>, the expression of tumour necrosis factor-stimulated gene-6 (TSG-6), the anti-inflammatory cytokine, was significantly higher in ADSC than in synovial cell (p&lt;0.01). The inflammatory cytokine levels in stimulated synovial cell were significantly decreased by ADSC treatment (p&lt;0.01) (table 1). <h3>Conclusions</h3> This is the first report to show the anti-inflammatory effect of ADSC for synovitis in RA animal model. ADSC can be collected with a minimally invasive technique more easily than other mesenchymal stem cells. ADSC might have potential to be one of the RA treatment. <h3>References</h3> [1] Pers YM, et al. Adipose derived stem cells for regenerative therapy in osteoarticular diseases. Horm Mol Biol Clin Investig2016Dec 1;28(3):113–120. [2] Sakaguchi N, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature2003;426:454–60. <h3>Disclosure of Interest</h3> None declared
Interactions of cancer stem cell and immune microenvironment in non-small cell lung cancer (NSCLC)
Authors: F. Zhang, N. Dong, S. Torres, S. Calabuig Fariñas, R. Sirera Perez, M. Mosqueda, E. Escorihuela, E. Jantus-Lewintre, C. Camps
Journal: Annals of Oncology (2018)
Colder Weather and Fewer Sunlight Hours Increase Alcohol Consumption and Alcoholic Cirrhosis Worldwide
Authors: Meritxell Ventura‐Cots, Ariel E. Watts, Monica Cruz‐Lemini, Neil D. Shah, Nambi Ndugga, Peter McCann, A. S. Barritt, Anant Jain, Samhita Ravi, Carlos Fernandez‐Carrillo, Juan G. Abraldes, Jose Altamirano, Ramon Bataller
Journal: Hepatology (2018)

Risk of alcoholic cirrhosis is determined by genetic and environmental factors. We aimed to investigate if climate has a causal effect on alcohol consumption and its weight on alcoholic cirrhosis. We collected extensive data from 193 sovereign countries as well as 50 states and 3,144 counties in the United States. Data sources included World Health Organization, World Meteorological Organization, and the Institute on Health Metrics and Evaluation. Climate parameters comprised Koppen‐Geiger classification, average annual sunshine hours, and average annual temperature. Alcohol consumption data, pattern of drinking, health indicators, and alcohol‐attributable fraction (AAF) of cirrhosis were obtained. The global cohort revealed an inverse correlation between mean average temperature and average annual sunshine hours with liters of annual alcohol consumption per capita (Spearman’s rho −0.5 and −0.57, respectively). Moreover, the percentage of heavy episodic drinking and total drinkers among population inversely correlated with temperature −0.45 and −0.49 ( P &lt; 0.001) and sunshine hours −0.39 and −0.57 ( P &lt; 0.001). Importantly, AAF was inversely correlated with temperature −0.45 ( P &lt; 0.001) and sunshine hours −0.6 ( P &lt; 0.001). At a global level, all included parameters in the univariable and multivariable analysis showed an association with liters of alcohol consumption and drinkers among population once adjusted by potential confounders. In the multivariate analysis, liters of alcohol consumption associated with AAF. In the United States, colder climates showed a positive correlation with the age‐standardized prevalence of heavy and binge drinkers. Conclusion: These results suggest that colder climates may play a causal role on AAF mediated by alcohol consumption.
All-cause mortality risk associated with long-term exposure to ambient PM2·5 in China: a cohort study
Authors: Tiantian Li, Yi Zhang, Jiaonan Wang, Dandan Xu, Zhaoxue Yin, Huashuai Chen, Yuebin Lv, Jiesi Luo, Yi Zeng, Yang Liu, Patrick L Kinney, Xiaoming Shi
Journal: The Lancet Public Health (2018)

Evidence from cohort studies in North America and Europe indicates that long-term exposure to fine particulate matter (PM2·5) is associated with an increased mortality risk. However, this association has rarely been quantified at higher ambient concentrations. We estimated the hazard ratio (HR) for all-cause mortality from long-term exposure to PM2·5 in a well established Chinese cohort of older adults.The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a prospective cohort study of men and women aged 65 years and older enrolled in 2008 and followed up through 2014 for mortality events. We studied individuals for whom residential locations were available in 2008 for linkage to 1 km grids of PM2·5 concentrations, derived from satellite remote sensing. Cox proportional hazards models were used to estimate the effect of long-term exposure to PM2·5 on all-cause mortality, controlling for age, sex, smoking status, drinking status, physical activity, body-mass index, household income, marital status, and education. We then used our results to estimate premature mortality related to PM2·5 exposure in the population aged 65 years and older in China in 2010.13 344 individuals in the CLHLS cohort had data for all timepoints, yielding follow-up data for 49 440 person-years. In a 3-year window, these individuals were exposed to a median PM2·5 concentration of 50·7 μg/m3 (range 6·7-113·3). The overall HR for a 10 μg/m3 increase in this value was 1·08 (95% CI 1·06-1·09). In stratified analyses, HRs were higher in rural than in urban locations, in southern versus northern regions, and with exposure to lower versus higher PM2·5 concentrations. Based on the overall HR, we estimated that 1 765 820 people aged 65 years and older in China in 2010 had premature mortality related to PM2·5 exposure.Long-term exposure to PM2·5 is associated with an increased risk of all-cause mortality among adults aged 65 years and older in China, but the magnitude of the risk declines as the concentration of PM2·5 increases.National Natural Science Foundation of China, National High-Level Talents Special Support Plan of China for Young Talents, US National Aeronautics and Space Administration, and the Columbia University Global Policy Initiative.
Tuberculosis in the European Union and European Economic Area: a survey of national tuberculosis programmes
Authors: Simon M. Collin, Gerard de Vries, Knut Lönnroth, Giovanni Battista Migliori, Ibrahim Abubakar, Sarah R. Anderson, Dominik Zenner
Journal: European Respiratory Journal (2018)

How many European Union (EU) and European Economic Area (EEA) countries have national tuberculosis (TB) control plans/strategies, and what are the priority actions/populations and barriers to implementation? In order to answer this question, a survey of EU/EEA national TB programme leads was undertaken. The response rate was 100% (31 countries). 55% of countries reported having a national TB strategy, all of which were in implementation; five countries were preparing a strategy. 74% had a defined organisational TB control structure with central coordination and 19% had a costed programme budget; few organisational structures included patient/civil society representation. The most frequently mentioned priority TB control actions were: reaching vulnerable population groups (80%), screening for active TB in high-risk groups (63%), implementing electronic registries (60%), contact tracing and outbreak investigation (60%), and tackling multidrug-resistant TB (60%). Undocumented migrants were the most commonly (46%) identified priority population. Perceived obstacles to implementation included barriers related to care recipients (lack of TB knowledge, treatment seeking/adherence), care providers (including need for specialist training of nurses and doctors) and health system constraints (funding, communication between healthcare and social care systems). This survey has provided an insight into TB control programmes across the EU/EEA that will inform the development of a TB strategy toolkit for member states.
P3.11-14 Low Rates of Lung Cancer Screening Among Doctors in Mexico
Authors: O. Macedo-Pérez, S. Campos-Gomez, M. Enríquez-Aceves, F. Talavera-Caro, I. Lyra-González, K. Campos-Peralta, E. Jiménez-Fuentes
Journal: Journal of Thoracic Oncology (2018)
Progestin, Not Progesterone
Authors: Henry H. Lindner
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
MPs slam “outrageous” 25% uptake of flu vaccine among social care staff
Authors: Jacqui Thornton
Journal: BMJ (2018)

MPs have criticised the low uptake of flu vaccination among staff in social care settings, putting it at best around 25%, far lower than the rate among frontline NHS staff.1

The House of Commons Science and Technology Committee carried out an inquiry into uptake after the high burden of flu seen in 2017-18, high numbers of hospital admissions, and evidence of variable uptake of the flu vaccine.

In March 2018 the committee held a one-off oral evidence session on the flu vaccination programme and heard from Public Health England, …
Abstract 17519: Diabetes Does Not Influence Long-Term Coverage on Top of the Everolimus-Eluting Bioresorbable Vascular Scaffold: A Longitudinal Porcine Optical Coherence Tomography Study
Authors: Nienke S van Ditzhuijzen, Mie Kurata, Oana Sorop, Mieke van den Heuvel, Richard van Duin, Ilona Krabbendam-Peters, Jurgen Ligthart, Karen Witberg, Patrick Serruys, Richard Rapoza, Felix Zijlstra, Dirk Duncker, Evelyn Regar, Heleen van Beusekom
Journal: Circulation (2013)

Diabetes mellitus (DM) remains a risk factor for restenosis after percutaneous coronary intervention despite the success of drug eluting stents. Whether DM also affects the vascular response to res...
CLINICAL APPLICATIONS OF SYNTHETIC ANGIOTENSIN II ANALOGUE
Authors: Toshio Ogihara, Toshihide Yamamoto, Yuichi Kumahara
Journal: Circulation (1974)

[1-sarcosine, 8-isoleucine] angiotensin II ([sar1 ile8] A II), one of the synthetic angiotensin II analogs, is a potent and 'long-lasting angiotensin II antagonist, whose competitive antagonism against pressor action of angiotensin II has been demonstrated in laboratory animals. Herein preliminary results of clinical applications of this compound were presented. There were no appreciable changes in urinalysis, complete blood counts and other routine laboratory tests, 6 and 24 hours after i.v. administration of 0.25mg [sar1, ile8] A 11 in 5 normal men. Transient elevation of blood pressure was observed after i.v. injection of 0.25mg for five minutes but not after i.v. infusion of the same dose for 30 minutes. Dose-related blockade of angiotensin II induced hypertension. was seen by concomitant administration of [sar1, ile8 J A II. The anti-angiotensin 11 action of [sar1 ile8 J A 11 became manifest in 5 minutes after the initiation of [sar1, ile8] A 11 infusion and lasted as long as 1 hour after the cessation of the infusion. The effect of this compound was tested in selected kinds of human hypertension. No reduction of blood pressure was observed in 6 subjects with essential hypertension. One subject with malignant hypertension and one with angiography-proved unilateral renovascular hypertension showed more than 20mmHg reduction in both systolic and diastolic blood pressure, whose duration of hypertension was estimated to be less than one year. Seven other hypertensive subjects, renovascular or malignant, showed negative response and one other subject with renovascular hypertension showed intermediate response to [sar1, ile8] A II. It appears that [sar1, ile8] A 11 per se does not have property of reducing blood pressure and that it reduces blood pressure by conuteracting angiotensin II. It is suggested that angiotensin 11 is involved in the development and/or main-tenanee of human hypertension at least of relatively short duration, acompanied by elevated plasma renin activity.
Blistering Distal Dactylitis
Authors: Robert Kowtoniuk, Robert Bednarek, Michele Maroon
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review
Authors: Thomas Van den Broeck, Roderick C.N. van den Bergh, Nicolas Arfi, Tobias Gross, Lisa Moris, Erik Briers, Marcus Cumberbatch, Maria De Santis, Derya Tilki, Stefano Fanti, Nicola Fossati, Silke Gillessen, Jeremy P. Grummet, Ann M. Henry, Michael Lardas, Matthew Liew, Olivier Rouvière, Jakub Pecanka, Malcolm D. Mason, Ivo G. Schoots, Theo H. van Der Kwast, Henk G. van Der Poel, Thomas Wiegel, Peter-Paul M. Willemse, Yuhong Yuan, Thomas B. Lam, Philip Cornford, Nicolas Mottet
Journal: European Urology (2018)
Pathologic differential diagnosis of metastatic carcinoma in the liver
Authors: Jeong Hwan Park, Jung Ho Kim
Journal: Clinical and Molecular Hepatology (2018)

The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.
Impact of initial treatment (tx) on HRQoL and outcomes in patients (pts) with newly diagnosed multiple myeloma (NDMM) without intent for immediate transplant (SCT): Results from the Connect® MM registry
Authors: R. Abonour, R.M. Rifkin, C. Gasparetto, K. Toomey, B.G.M. Durie, J.W. Hardin, H.R. Terebelo, S. Jagannath, M. Narang, S. Ailawadhi, S. Srinivasan, A. Kitali, A. Agarwal, L. Wagner
Journal: Annals of Oncology (2018)
P3.16-09 High Preoperative D-Dimer Level Predicts Early Recurrence After Surgery for Non-Small Cell Lung Cancer
Authors: Y. Shiina, T. Nakajima, T. Kaiho, K. Ohashi, Y. Sata, A. Hata, T. Toyoda, T. Yamamoto, J. Morimoto, Y. Sakairi, H. Wada, H. Suziki, I. Yoshino
Journal: Journal of Thoracic Oncology (2018)