bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease
Authors: Vinereanu Dragos , Wang Alice , Mulder Hillary , Lopes Renato D , Jansky Petr , Lewis Basil S , Gersh Bernard J , Avezum Alvaro , Hanna Michael , Held Claes , Wallentin Lars , Granger Christopher B , Alexander John H
Published: January 2018

Objective

To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.

Methods

There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.

Results

Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.

Conclusions

In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.

Clinical trial registration

ARISTOTLE clinical trial numberNCT00412984.
Incidence, predictors and clinical outcomes of residual stenosis after aortic valve-in-valve
Authors: Bleiziffer Sabine , Erlebach Magdalena , Simonato Matheus , Pibarot Philippe , Webb John , Capek Lukas , Windecker Stephan , George Isaac , Sinning Jan-Malte , Horlick Eric , Napodano Massimo , Holzhey David M , Petursson Petur , Cerillo Alfredo , Bonaros Nikolaos , Ferrari Enrico , Cohen Mauricio G , Baquero Giselle , Jones Tara L , Kalra Ankur , Reardon Michael J , Chhatriwalla Adnan , Gama Ribeiro Vasco , Alnasser Sami , Van Mieghem Nicolas M , Rustenbach Christian Jörg , Schofer Joachim , Garcia Santiago , Zeus Tobias , Champagnac Didier , Bekeredjian Raffi , Kornowski Ran , Lange Rüdiger , Dvir Danny
Published: January 2018

Objective

We aimed to analyse the incidence of prosthesis–patient mismatch (PPM) and elevated gradients after aortic valve in valve (ViV), and to evaluate predictors and associations with clinical outcomes of this adverse event.

Methods

A total of 910 aortic ViV patients were investigated. Elevated residual gradients were defined as ≥20 mm Hg. PPM was identified based on the indexed effective orifice area (EOA), measured by echocardiography, and patient body mass index (BMI). Moderate and severe PPM (cases) were defined by European Association of Cardiovascular Imaging (EACVI) criteria and compared with patients without PPM (controls).

Results

Moderate or greater PPM was found in 61% of the patients, and severe in 24.6%. Elevated residual gradients were found in 27.9%. Independent risk factors for the occurrence of lower indexed EOA and therefore severe PPM were higher gradients of the failed bioprosthesis at baseline (unstandardised beta −0.023; 95% CI −0.032 to –0.014; P<0.001), a stented (vs a stentless) surgical bioprosthesis (unstandardised beta −0.11; 95% CI −0.161 to –0.071; P<0.001), higher BMI (unstandardised beta −0.01; 95% CI −0.013 to –0.007; P<0.001) and implantation of a SAPIEN/SAPIEN XT/SAPIEN 3 transcatheter device (unstandardised beta −0.064; 95% CI −0.095 to –0.032; P<0.001). Neither severe PPM nor elevated gradients had an association with VARC II-defined outcomes or 1-year survival (90.9% severe vs 91.5% moderate vs 89.3% none, P=0.44).

Conclusions

Severe PPM and elevated gradients after aortic ViV are very common but were not associated with short-term survival and clinical outcomes. The long-term effect of poor post-ViV haemodynamics on clinical outcomes requires further evaluation.
Effectiveness of comprehensive social support interventions among elderly patients with tuberculosis in communities in China: a community-based trial
Authors: Li Xuhui , Wang Bin , Tan Dixin , Li Mengyu , Zhang Dandan , Tang Cong , Cai Xiaonan , Yan Yaqiong , Zhang Sheng , Jin Bo , Yu Songlin , Liang Xunchang , Chu Qian , Xu Yihua
Published: January 2018

Background

With the increasing of ageing population, tuberculosis in the elderly brings a challenge for the tuberculosis (TB) control in China. Enough social support can promote the treatment adherence and outcome of the elderly patients with TB. Exploring effective interventions to improve the social support of patients is of great significance for TB management and control.

Methods

A community-based, repeated measurement trial was conducted. Patients with TB >65 years of age were allocated into the intervention or control group. Patients in the intervention group received comprehensive social support interventions, while those in the control group received health education alone. The social support level of patients was measured at baseline and at the first, third and sixth months during the intervention to assess the effectiveness of comprehensive social support interventions.

Results

A total of 201 patients were recruited into the study. Compared with the control group, social support for patients in the intervention group increased significantly over time (βgroup*time=0.61, P<0.01) in the following three dimensions: objective support (βgroup*time=0.15, P<0.05), subjective support (βgroup*time=0.32, P<0.05) and support utilisation (βgroup*time=0.16, P<0.05). The change in the scores in the control group was not statistically significant.

Conclusions

The intervention programme in communities, including health education, psychotherapy and family and community support interventions, can improve the social support for elderly patients with TB compared with single health education.

Trial registration number

ChiCTR-IOR-16009232
Prevalence of invehicle smoking and secondhand smoke exposure in Uruguay
Authors: Llambi Laura , Barros Mary , Parodi Carolina , Pippo Antonella , Nunez Virginia , Colomar Mercedes , Ciganda Alvaro , Cavalleri Fiorella , Goyeneche Juan J , Aleman Alicia
Published: January 2018

Introduction

Protection from secondhand smoke (SHS) is one of the fundamental principles of the WHO Framework Convention for Tobacco Control. Objective data on SHS exposure in vehicles in South America is scarce. This study aimed to estimate prevalence of smoking inside vehicles.

Methods

The point prevalence of smoking in vehicles was observed, and a method for estimating smoking prevalence was piloted.

Results

We observed 10 011 vehicles. In 219 (2.2%; 95% CI 1.91 to 2.49) of them, smoking was observed, and in 29.2% of these, another person was exposed to SHS. According to the ‘expansion factor’ we constructed, direct observation detected one of six to one to nine vehicles in which smoking occurred. The observed prevalence of smoking in vehicles (2.2%) could reflect a real prevalence between 12% and 19%. In 29.2% (95% CI 23.6 to 35.5) and 4.6% (95% CI 2.2 to 8.3) of vehicles in which smoking was observed, another adult or a child, respectively, was exposed to SHS.

Conclusions

Smoking was estimated to occur in 12%–19% of vehicles, with involuntary exposure in one of three of vehicles observed. These data underscore a need for new public policies to eliminate SHS in vehicles to protect public health.
An Improved Biologically-Inspired Image Fusion Method
Authors: Wang Yuqing , Wang Yong
Published: January 2018

A biologically inspired image fusion mechanism is analyzed in this paper. A pseudo-color image fusion method is proposed based on the improvement of a traditional method. The proposed model describes the fusion process using several abstract definitions which correspond to the detailed behaviors of neurons. Firstly, the infrared image and visible image are respectively ON against enhanced and OFF against enhanced. Secondly, we feed back the enhanced visible images given by the ON-antagonism system to the active cells in the center-surrounding antagonism receptive field. The fused [Formula: see text]VIS[Formula: see text]IR signal are obtained by feeding back the OFF-enhanced infrared image to the corresponding surrounding-depressing neurons. Then we feed back the enhanced visible signal from OFF-antagonism system to the depressing cells in the center-surrounding antagonism receptive field. The ON-enhanced infrared image is taken as the input signal of the corresponding active cells in the neurons, then the cell response of infrared-enhance-visible is produced in the process, it is denoted as [Formula: see text]IR[Formula: see text]VIS. The three kinds of signal are considered as R, G and B components in the output composite image. Finally, some experiments are performed in order to evaluate the performance of the proposed method. The information entropy, average gradient and objective image fusion measure are used to assess the performance of the proposed method objectively. Some traditional digital signal processing-based fusion methods are also evaluated for comparison in the experiments. In this paper, the Quantitative assessment indices show that the proposed fusion model is superior to the classical Waxman’s model, and some of its performance is better than the other image fusion methods.
Visual Neural Network Model for Welding Deviation Prediction Based on Weld Pool Centroid
Authors: Ding Dukun
Published: January 2018

To solve the problem in the process of weld seam tracking, a new prediction model for welding deviation based on the weld pool image centroid has been proposed in the paper. First, some weld images under different weld currents were captured by a vision sensor. A composite filter system, which is composed of narrow-band and neutral filters, is used to reduce the disturbance of weld arc. So, several clear weld pool images can be obtained. Then a frontier of weld pool is chosen to be the processing region. Median filter and gray transformation operations are used to enhance the contrast of processing region. On this basis, the variation trend of centroid difference [Formula: see text] and welding deviation [Formula: see text] were analyzed. The centroid difference value [Formula: see text] and the weld current [Formula: see text] were determined to be welding status parameters. Moreover, a BP neural network was set up, which was composed of three layers. Next, elastic gradient descent method was used to be the training function. So a prediction model between the welding status parameters [Formula: see text] and [Formula: see text] and the welding deviation [Formula: see text] was set up. In the end of the paper, several experiments were performed to test the accuracy of the setup prediction model. The results showed that prediction values of welding deviation calculated by the vision model are fit to the real measured values. The final errors of the vision model under the weld current 70[Formula: see text]A and 73[Formula: see text]A were 0.033[Formula: see text]mm and 0.027[Formula: see text]mm, which showed excellent accuracy, environmental suitability and intelligence of the model.
Performance Comparison Between Current-Mode Signaling and Voltage-Mode Signaling for Single-Walled Carbon Nanotube Bundle Interconnects
Authors: Zhao Songjie , Pan Zhongliang
Published: January 2018

Compared with the traditional copper material, carbon nanotube (CNT) has been identified as one of the most potential materials for interconnects in nanometer regime due to higher performance. However, for CNT interconnects, most of the researches focus on voltage-mode signaling (VMS) scheme, whereas current-mode signaling scheme (CMS) is meagerly investigated. The paper proposes an equivalent circuit model of two-line coupled single-walled CNT bundle interconnects, which is applicable to both CMS and VMS schemes. In addition, the model takes capacitive and inductive crosstalk into consideration. In CMS and VMS interconnects, the performance of victim line in the time domain is studied according to decoupling technique and ABCD parameter matrix approach at local, intermediate and global levels, respectively. The influence of aggressor line on victim line is discussed because of dynamic crosstalk and functional crosstalk. Furthermore, the paper comparatively analyzes the performance advantage between CMS interconnects and VMS interconnects. The results show that CMS interconnects have lower output voltage swing and propagation delay than VMS interconnects in the same condition. In terms of noise, CMS scheme has higher advantage for lesser noise peak, noise width and noise area. Moreover, it is found that the results obtained by ABCD parameter matrix approach have great consistency with Advanced Design System simulation results.
Specific Heat Investigation in Iron-Based Superconductors
Authors: Pradhan B. , Goi S. K. , Mishra R. N.
Published: January 2018

We have proposed a mean field theoretical model in the coexistence of superconductivity and Jahn–Teller (JT) effect for the study of specific heat in iron-based superconductors in the presence of an external magnetic field. The superconducting (SC) gap and lattice strain energy expressions are calculated using Zubarev’s technique of double-time electron Green’s function and solved numerically. The specific heat jump at the critical temperatures are observed. Keeping fixed the SC transition temperature at 28[Formula: see text]K for the iron pnictide [Formula: see text] like superconductors, the coefficient of electronic specific heat [Formula: see text] at low temperatures is determined to be 5.75[Formula: see text]mJ/mol[Formula: see text]K2 in the pure SC state and 4.76[Formula: see text]mJ/mol[Formula: see text]K2 in the coexistence state of SC and JT effect which are in agreement with some experimental results. The effect of the external magnetic field on the specific heat is studied.
Enzymes in Lipid Modification
Authors: Bornscheuer Uwe T.
Published: January 2018

This article reviews the application of enzymes in lipid modification. Lipases are the most established biocatalysts used for the synthesis of structured triacylglycerols, fats, and margarine and for the release of flavoring fatty acids for food applications. In addition, the various enzymes, such as P450 monooxygenases, hydratases, lipoxygenases, and certain lyases, used for oxyfunctionalization and the phospholipases used for degumming are covered. Basic aspects of enzyme catalysis and the modern tools used for their discovery and improvement by protein engineering provide insight into how suitable biocatalysts can be identified and optimized for an application. In addition to isolated enzymes, whole-cell engineered microorganisms are also used for lipid modification. Thus, the polyunsaturated fatty acid EPA (eicosapentaenoic acid) can be produced in a yeast using sugar as a renewable resource.
Formation, Structure, and Functionality of Interfacial Layers in Food Emulsions
Authors: Berton-Carabin Claire C. , Sagis Leonard , Schroën Karin
Published: January 2018

Emulsions, i.e., the dispersion of liquid droplets in a nonmiscible liquid phase, are overwhelmingly present in food products. In such systems, both liquid phases (generally, oil and water) are separated by a narrow region, the oil-water interface. Despite the fact that this interface is very thin (in the nanometer range), it represents a large surface area and controls to a great extent the physicochemical stability of emulsions. This review provides an overview of the aspects that govern the composition, structure, and mechanical properties of interfaces in food emulsions, taking into account the complexity of such systems (presence of numerous surface-active molecules, influence of processing steps, and dynamic evolution due to chemical changes). We also review methods that have conventionally, or recently, been used to study liquid-liquid interfaces at various scales. Finally, we focus on the link between interfacial properties and the physical, chemical, and digestive stability of emulsions at different levels and point out trends to control stability via interfacial engineering.
Dietary Advanced Glycosylation End-Products (dAGEs) and Melanoidins Formed through the Maillard Reaction: Physiological Consequences of their Intake
Authors: Delgado-Andrade Cristina , Fogliano Vincenzo
Published: January 2018

The main purpose of this review is to clarify whether the consumption of food rich in melanoidins and dietary advanced glycosylation end-products (dAGEs) is harmful or beneficial for human health. There are conflicting results on their harmful effects in the literature, partly due to a methodological issue in how dAGEs are determined in food. Melanoidins have positive functions particularly within the gastrointestinal tract, whereas the intake of dAGEs has controversial physiological consequences. Most of the in vivo intervention trials were done comparing boiled versus roasted diet (low and high dAGE, respectively). However, these studies can be biased by different lipid oxidation and by different calorie density of foods in the two conditions. The attraction that humans have to cooked foods is linked to the benefits they have had during mankind's evolution. The goal for food technologists is to design low-energy-dense products that can satisfy humans’ attraction to rewarding cooked foods.
ERα-Mediated Nuclear Sequestration of RSK2 Is Required for ER+ Breast Cancer Tumorigenesis
Authors: Ludwik Katarzyna A. , McDonald Oliver G. , Brenin David R. , Lannigan Deborah A.
Published: January 2018

Although ribosomal protein S6 kinase A3 (RSK2) activation status positively correlates with patient responses to antiestrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of estrogen receptor–positive (ER+) breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N terminus to activate a proneoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status. ER+ tumor growth was strongly dependent on nuclear RSK2, and transgenic mice engineered to stably express nuclear RSK2 in the mammary gland developed high-grade ductal carcinoma in situ. Mammary cells isolated from the transgenic model and introduced systemically successfully disseminated and established metastatic lesions. Antiestrogens disrupted the interaction between RSK2 and ERα, driving RSK2 into the cytoplasm and impairing tumor formation. These findings establish RSK2 as an obligate participant of ERα-mediated transcriptional programs, tumorigenesis, and divergent patient responses to antiestrogen therapies.

Significance: Nuclear accumulation of active RSK drives a protumorigenic transcriptional program and renders ER+ breast cancer susceptible to endocrine-based therapies. Cancer Res; 78(8); 2014–25. ©2018 AACR.
Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors
Authors: Asiedu Michael K. , Thomas Charles F. , Dong Jie , Schulte Sandra C. , Khadka Prasidda , Sun Zhifu , Kosari Farhad , Jen Jin , Molina Julian , Vasmatzis George , Kuang Ray , Aubry Marie Christine , Yang Ping , Wigle Dennis A.
Published: January 2018

Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors.

Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum.

Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1. The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1. Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C>T and T>C transitions with a minor contribution of T>G transversions.

Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res; 24(7); 1691–704. ©2018 AACR.
High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Authors: Diets Illja J. , Waanders Esmé , Ligtenberg Marjolijn J. , van Bladel Diede A.G. , Kamping Eveline J. , Hoogerbrugge Peter M. , Hopman Saskia , Olderode-Berends Maran J. , Gerkes Erica H. , Koolen David A. , Marcelis Carlo , Santen Gijs W. , van Belzen Martine J. , Mordaunt Dylan , McGregor Lesley , Thompson Elizabeth , Kattamis Antonis , Pastorczak Agata , Mlynarski Wojciech , Ilencikova Denisa , van Silfhout Anneke Vulto- , Gardeitchik Thatjana , de Bont Eveline S. , Loeffen Jan , Wagner Anja , Mensenkamp Arjen R. , Kuiper Roland P. , Hoogerbrugge Nicoline , Jongmans Marjolijn C.
Published: January 2018

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer.

Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome.

Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein–Taybi syndrome, ARID1A-based Coffin–Siris syndrome, ACTB-based Baraitser–Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition.

Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. Clin Cancer Res; 24(7); 1594–603. ©2018 AACR.
Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Authors: Bellone Stefania , Buza Natalia , Choi Jungmin , Zammataro Luca , Gay Laurie , Elvin Julia , Rimm David L. , Liu Yuting , Ratner Elena S. , Schwartz Peter E. , Santin Alessandro D.
Published: January 2018

Purpose: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed.

Patients and Methods: We describe a heavily pretreated patient with ovarian cancer with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune checkpoint inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (i.e., automated quantitative analysis, AQUA) and whole-exome sequencing (WES) techniques.

Results: The patient harbored a recurrent/metastatic radiation and chemotherapy-resistant high-grade ovarian carcinoma with clear cell features. While progressing on any standard treatment modality, she demonstrated a remarkable complete response to the anti-PD1 immune checkpoint inhibitor pembrolizumab. WES results were notable for the presence a relative low number of mutations (tumor mutation load/Mb = 4.31, total mutations = 164) and a peculiar structural variant disrupting the 3′ region of the PD-L1 gene causing aberrant PD-L1 surface expression as confirmed by IHC and AQUA technology. Heavy infiltration of the PD-L1–mutated and PD-L1–overexpressing tumor with T-cell lymphocytes (i.e., CD4+/CD8+ TIL), CD68+ macrophages, and CD20+ B cells was detected in the surgical specimen strongly suggesting immune evasion as a key mechanism of tumor growth and survival. Patient's complete clinical responses remain unchanged at the time of the writing of this report with no significant side effects reported to date.

Conclusions: Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring PD-L1 gene structural variations causing aberrant PD-L1 expression. Clin Cancer Res; 24(14); 3282–91. ©2018 AACR.

See related commentary by Lheureux, p. 3233
Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by PELP1/AIB1 Complexes
Authors: Truong Thu H. , Hu Hsiangyu , Temiz Nuri A. , Hagen Kyla M. , Girard Brian J. , Brady Nicholas J. , Schwertfeger Kathryn L. , Lange Carol A. , Ostrander Julie H.
Published: January 2018

Proline, glutamic acid, leucine-rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, interacting partners unique to cytoplasmic PELP1 and the mechanisms by which these interactions promote oncogenic PELP1 signaling were sought. AIB1 (amplified in breast cancer 1; also known as SRC-3 or NCOA3) was identified as a novel binding partner of cytoplasmic PELP1 in both estrogen receptor–positive (ER+) and ER-negative cell lines. Cytoplasmic PELP1 expression elevated basal phosphorylation levels (i.e., activation) of AIB1 at Thr24, enhanced ALDH+ tumorsphere formation, and upregulated specific target genes independently of hormone stimulation. Direct manipulation of AIB1 levels using shRNA abrogated cytoplasmic PELP1-induced tumorsphere formation and downregulated cytoplasmic PELP1-specific target genes. SI-2, an AIB1 inhibitor, limited the PELP1/AIB1 interaction and decreased cytoplasmic PELP1-induced tumorsphere formation. Similar results were observed in a murine-derived MMTV-AIB1 tumor cell line. Furthermore, in vivo syngeneic tumor studies revealed that PELP1 knockdown resulted in increased survival of tumor-bearing mice as compared with mice injected with control cells.

Implications: These data demonstrate that cytoplasmic PELP1/AIB1–containing complexes function to promote advanced cancer phenotypes, including outgrowth of stem-like cells, associated with estrogen-independent breast cancer progression. Mol Cancer Res; 16(4); 707–19. ©2018 AACR.
What Can Google Inform Us about People's Interests regarding Dental Caries in Different Populations?
Authors: Aguirre Patricia Estefania , Coelho Melina , Oliveira Thaís , Rios Daniela , Cruvinel Agnes Fátima , Cruvinel Thiago
Published: January 2018

The diagnosis or suspicion of dental caries can lead people to seek additional information on the Internet through the use of structured queries in search engine tools. This action generates a considerable volume of data, which can be analyzed to provide a better understanding of the public's behavior linked to the consumption of oral health information. This study aimed to assess the volume and profile of web searches on dental caries-related queries performed by Google users from different countries. The monthly variation of the Search Volume Index (SVI) for dental caries was obtained in Google Trends for the period between January 2004 and September 2016. The validity of SVI data was assessed by their levels of stability and correlation with the disability-adjusted life-years (DALYs) for permanent teeth. In all countries, a trend of an increasing interest of Google users in dental caries issues was revealed by the comparison of the means observed in the predictive models and those in the last 12 months. The interest levels varied throughout the year, with the observation of the highest SVI values in the spring and the lowest in the summer. The most popular queries were markedly associated with symptoms and treatments, with a little interest in prevention. In conclusion, the use of Internet data mining could be helpful in establishing the dental needs of specific population groups in a near real-time, since the web consumption of dental information is increasing in importance and appears to have a direct relation with untreated dental caries.
Clinical Characteristics and Allergen Sensitization Patterns of Patients with Local Allergic Rhinitis in Southern China
Authors: Tao Xiao Yao , Ng Chew Lip , Chen Dong , Lin Zhi Bin , Wu Shu Lian , Liang Mei Jun , Li Chun Wei , Xu Rui
Published: January 2018

Background: Local allergic rhinitis (LAR) is characterized by the production of specific IgE (sIgE) in the nasal mucosa without evidence of systemic atopy. The characteristics of LAR in Caucasians have been well documented. LAR is understudied in China, with prevalence, patient demographics, symptomatology, and the allergen sensitization profile being poorly understood. The purpose of this study is to investigate the demographics, characteristics, and allergen sensitization profile of patients with LAR in Southern China. Methods: A total of 194 patients with rhinitis and 13 healthy subjects were enrolled in the current study. The patients' demographic data, clinical history, and symptoms were recorded. Local and systemic sIgE to a wide panel of specific allergens were measured in the nasal secretion and serum samples. Results: Among the rhinitis patients, 115 were classified as allergic rhinitis (AR; 59.3%), 15 as LAR (7.7%), and 64 as non-AR (33.0%). The demographic characteristics, duration, frequency, and severity of symptoms were similar, although LAR exhibited higher symptom scores for nasal itch. Monosensitization was the predominant pattern of sensitization in both AR (109 out of 115, 95%) and LAR (14 out of 15, 93%). House dust mite was the dominant allergen in AR patients (109 out of 115, 95%), while pollen was the dominant allergen in LAR patients (11 out of 15, 73%). Conclusion: The prevalence of LAR patients in Southern China was 7.7%. Pollen was the most common sensitizing allergen for the local LAR patients, which differs from Caucasian studies, in which house dust mite was the dominant sensitizing allergen. Monosensitization was the predominant pattern in both AR and LAR.
Clinical Heterogeneity in Familial IgA Nephropathy
Authors: Fennelly Neil K. , Kennedy Claire , Jenkinson Allan C. , Connaughton Dervla M. , Stapleton Caragh , Dorman Anthony M. , Doyle Brendan , Conlon Peter J.
Published: January 2018

Background: IgA nephropathy is the most common primary glomerulonephritis worldwide and a significant cause of end-stage renal disease (ESRD). While most cases of IgA nephropathy are considered sporadic, familial cases have been reported. Methods: We performed a national audit of 1,809 patients attending renal clinics and dialysis units to identify a family history among patients with kidney disease. We reviewed all renal biopsies performed at our institution spanning a 30-year period. Paediatric cases were not included. Results: We identified 14 families involving 41 affected individuals with biopsy-proven IgA nephropathy and at least one other member with either biopsy-proven IgA nephropathy or ESRD. Detailed family histories were obtained, medical records reviewed and family pedigrees constructed. Retrospective application of the MESTC criteria to all familial IgA biopsies was performed. Seven families had 2 or more members with biopsy-proven IgA nephropathy, equating to 23 (1.8%) of 1,283 biopsies with IgA nephropathy over the last 30 years. A complex inheritance pattern was observed, with autosomal dominant and autosomal recessive families identified with varying penetrance. There was a male preponderance (68%), and a complex heterogeneity in the clinical and histopathological features of familial IgA patients (age range 16–60 years; creatinine range 60–350 μmol/L). We observed a high rate (66%) of progression to ESRD, with a mean time to progression of 5.13 years (SD 1.8 years; range 2–8 years). Among those patients who had undergone transplantation, recurrence of disease was reported in 5 (50%) cases. Conclusion: These data suggests familial aggregation of IgA nephropathy, confirm the clinical and histopathological heterogeneity and raise the possibility of monogenic inheritance.
Non-Invasive Diagnostic Criteria for Hepatocellular Carcinoma in Hepatitis B Virus-Endemic Areas: Is Cirrhosis Indispensable?
Authors: Huang Xiao-wen , Liao Bing , Huang Yang , Liang Jin-yu , Shan Quan-yuan , Shen Shun-li , Xie Xiao-yan , Lu Ming-de , Chen Li-da , Wang Wei
Published: January 2018

Aim: To confirm whether cirrhosis is indispensable for the non-invasive diagnostic criteria for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-endemic areas. Methods: Between January 2014 and December 2014, a total of 409 patients with pathologically proven focal liver lesions who underwent contrast-enhanced ultrasound (CEUS) were recruited from our institution. Clinical liver cirrhosis, HBV/HCV infection and HCC-typical vascular pattern of the targeted lesion on CEUS were evaluated. The following 3 criteria were applied to these patients to diagnose HCC: criterion 1, clinical liver cirrhosis and HCC-typical vascular pattern; criterion 2, HBV/HCV infection and HCC-typical vascular pattern; criterion 3, HBV/HCV infection or clinical liver cirrhosis and HCC-typical vascular pattern. Pathological reports were considered the gold standard. Results: A total of 311 patients had confirmed HCC by pathology. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and area under the ROC curve for criterion 1 were 29.6, 90.8, 44.3, 91.1, 28.9, and 0.60% respectively. For criterion 2, they were 83.3, 74.5, 81.2, 91.2, 58.4, and 0.79%, respectively, and for criterion 3, they were 86.2, 72.5, 82.9, 90.9, 62.3, and 0.79% respectively. Conclusions: In HBV-endemic areas, when using the HBV/HCV infection instead of cirrhosis as the precondition of the non-invasive diagnostic criteria for HCC, we should be aware of the potential false positive. Cirrhosis still plays an important role in the non-invasive diagnostic criteria for HCC because of the high specificity.
Metabolomics in Sepsis and Its Impact on Public Health
Authors: Evangelatos Nikolaos , Bauer Pia , Reumann Matthias , Satyamoorthy Kapaettu , Lehrach Hans , Brand Angela
Published: January 2018

Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of “-omics” technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an “-omics” technology further down in the “-omics” cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software.
A formação da nação brasileira
Authors: Oberacker Junior Carlos H.
Published: January 2018

A nossa finalidade era a de demonstrar que a formação da nação brasileira tenha sido um processo meramente histórico, liberto das interdependências antecedentes biológicas e raciais. Supomos que o conseguimos através destas considerações. Pretendemos, ao mesmo tempo, esboçar a importância do conceito "nação" para a historiografia brasileira. A idéia de nação, a nosso ver, não só permite uma exposição mais segura e mais panorâmica da história brasileira, mas também oferece o critério justo para aquilatar e apreciar os acontecimentos e as personalidades históricas, que só chegam a adquirir importância e significação por terem comparticipado e por estarem relacionadas com a formação da nação brasileira. Melhor e mais ampla explanação do assunto nos reservamos fazer em outros trabalhos.(último parágrafo do texto)
A propósito de Sevilha e o Atlântico no século XVI e meados do século XVII
Authors: Garcia Rozendo Sampaio
Published: January 2018

Depois que Fernand Paul Braudel publicou o seu admirável' "La Mediterranée au temps de Philippe II", inaugurando a via dos estudos dos mares do ponto de vista da história da economia, seria natural que se lançassem pesquisadores da têmpera dos Chaunu na busca do Atlântico espanhol, no período complementar. Apenas temos em mãos os dois primeiros exemplares duma, série monumental de oito volumes e já estamos prelibando o prazer da leitura dos restantes, bem como antevemos o despertar do interêsse pelo estudo do Atlântico português nessa mesma fase que animará, por certo, algum historiador dessa escola a ampliar os quadros dos conhecimentos de uma época apaixonante sob diversos prismas.
A ação dos bandeirantes paulistas no Nordeste - algumas achegas para o seu estudo
Authors: Coulter Antonia Fernanda de Almeida
Published: January 2018

(1. parágrafo do texto)O estudo do bandeirismo paulista no Nordeste não constitui, como é sabido, assunto inédito. Das andanças dos sertanistas paulistas pelo Nordeste estão crivados os trabalhos de Taunay, de Borges de Barros, de Basílio Magalhães, Inácio Accioli, Capistrano e tantos outros. A documentação apresentada por Borges de Barros nos Anais do Arquivo Histórico e Museu do Estado da Bahia nos volumes 1 a 5 é particularmente sugestiva.
Notas para o estudo das relações dos banqueiros alemães com o empreendimento colonial dos países ibéricos na América no século XVI
Authors: Schorer Maria Thereza
Published: January 2018

(primeiras cinco linhas do texto)"No fim do século XV e no comêço do século seguinte a Europa passou por incisivas transformações que há muito vinham se manifestando. Os ideais do Renascimento, os problemas religiosos, as novas teorias econômicas abalaram a consciência do homem ainda quase completamente prêso aos ideais medievais. (...)"
Resenha do livro 'El Epitome de Pinelo, primera bibliografia del Nuevo Mundo.'
Authors: Paula Eurípedes Simões de
Published: January 2018

CARLO, Agustin Millares. El Epitome de Pinelo, primera bibliografia del Nuevo Mundo. União Panamericana. Washington. 1958. XLIV + 186 + XII.
Aristóteles e os índios americanos: um estudo de preconceito de raça no Mundo Moderno
Authors: Hanke Lewis
Published: January 2018

(Primeiras linhas do texto)"Escritos recentes, sôbre a conquista espanhola da América bem ilustram o velho axioma que o trabalho do historiador nunca está pronto e que a história do passado precisa ser constantemente revista. (...)"
O crescimento de uma cidade francesa: Tolosa
Authors: Wolff Philippe
Published: January 2018

(Primeiras linhas do texto)"O desenvolvimento das cidades francesas apresenta evidentemente ao geógrafo um quadro muito diferente da imagem que lhe oferecem as cidades do Novo Mundo. Elas são, na maioria das vêzes, muito antigas; muitas delas poderiam, como recentemente Paris, festejar seus bi-milenários. (...)"
João Henrique Böhm, o fundador do exército brasileiro
Authors: Oberacker Junior Carlos H.
Published: January 2018

(Primeiras linhas do texto)"Durante a Guerra dos Sete Anos, quando em 17 de agôsto de 1761 as potências sob os Bourbons — França, Espanha e Parma — firmaram o chamado Pacto de Família para quebrantar o poderio inglês, exigiram por uma espécie de ultimatum a Portugal, aliado da Inglaterra, que fizesse parte dêsse Pacto, e acabaram por declarar guerra à nação insular, com a qual a França já em 1756 disputava a hegemonia mundial. (...)"
Resenha do livro "Caminhos e Fronteiras"
Authors: Steiner Maria Helena C. de Figueiredo
Published: January 2018

HOLANDA, Sérgio Buarque de. Caminhos e Fronteiras, Livraria José Olímpio Editôra, Rio de Janeiro, 1957, 334 págs. 25 ilustrações fora do texto.
Resumo do livro "The last stand of chinese conservatism. The T'ung-Chih Restoration"
Authors: Campos Pedro Moacyr
Published: January 2018

WRIGHT, Mary Clabaugh. The last stand of chinese conservatism. The T'ung-Chih Restoration, 1862-1874. Stanford University Press, Stanford, Califórnia, 1957, 426 págs.
Marcondes de Sousa e a historiografia contemporânea portuguesa
Authors: Levillier Roberto
Published: January 2018

A Revista de História de São Paulo acaba de reunir, sob o título de Algumas achegas à história dos descobrimentos marítimos (2), vinte artigos nela publicados sôbre êsse tema, pelo seu colabolador o Prof. T. O. Marcondes de Souza. Destaca-se nesses artigos o crítico penetrante, habituado a servir à cultura com erudição, valentia e elevados propósitos. Tais qualidades são duplamente apreciados neste caso porque a Revista de História (3) de São Paulo, órgão oficial do Departamento de História da Faculdade de Filosofia, Ciências e Letras da Universidade de São Paulo, é lida por um grande número de seus alunos e ex-alunos.
Memória histórica de São Sebastião (VII)
Authors: Almeida Antônio Paulino de
Published: January 2018

VULTOS NOTÁVEIS E PRIMEIROS TRONCOS DA FAMÍLIA SEBASTIANENSE. Como comprovante do que afirmamos na Introdução dêste modesto trabalho, e muito de propósito, escolhemos o presente capítulo para a sua parte final.
O café na evolução de São Paulo
Authors: Fernandes Florestan
Published: January 2018

Ninguém ignora que o café foi o principal fator do desenvolvimento econômico e da prosperidade de São Paulo. Graças ao café, a vida econômica de São Paulo saiu do marasmo em que se mantinha durante o fim do século XVIII e a primeira metade do século XIX e integrou-se, ràpidamente, no sistema econômico tropical, com profundas transformações no cenário natural e humano da região. O fenômeno ocorreu com tamanha rapidez, que mesmo os observadores mais argutos acaba-ram representando o café como um "fator" de povoamento, de enriquecimento e de progresso.
Noções de Numismática Brasileira (IV)
Authors: Coimbra Álvaro da Veiga
Published: January 2018

(Continuação)REINADO DE D. MARIA I E D. PEDRO III. 1777-1799. Emissões do reinado de D. Maria I e D. Pedro III. A moedagem de D. Maria I, viúva. Legendas e divisas das moedas de D. Maria I e D. Pedro III. A moedagem dêste reinado compreende duas fases distintas: 1a. A que vai de 24 de fevereiro de 1700, em que por morte de seu pai, o rei D. José I, sua filha D. Maria I, ascende ao trono e se prolonga até 25 de maio de 1786, data do falecimento de seu marido e tio, D. Pedro III. 2a. A viuvez e vai até 1799, quando D. João, Príncipe Regente, assume em caráter definitivo o govêrno, o que já vinha fazendo desde 2 de fevereiro de 1792, dado o precário estado de saúde da soberana.
Resenha de: Latin America: a History
Authors: Daglione Vivaldo Wenceslau Flor
Published: January 2018

THOMAS (Alfred Barnaby). — Latin America. A History. The Macmillan Company. New York, 1956 (1a. edição). 801 páginas.
Aspectos do comércio dos domínios portugueses no período de 1808 a 1821
Authors: Pantaleão Olga
Published: January 2018

A história do Império português, no que diz respeito à organização e às relações comerciais, oferece, no período de 1808 a 1821, aspectos interessantes. Aproveitando documentos existentes no Arquivo Nacional (Rio de Janeiro), principalmente documentos sôbre o movimento do comércio marítimo, pudemos fazer as observações que apresentamos neste trabalho.
Resenha de: Os Prologômenos ou Filosofia Social
Authors: Daglione Vivaldo Wenceslau Flor
Published: January 2018

IBN KHALDUN. — Os Prologômenos ou Filosofia Social. Tradução integral direta do árabe por José Khoury e Angelina Bierrenbach Khoury. Introdução de Jamil Almansur Haddad. Tomo primeiro. Instituto Brasileiro de Filosofia. Editora Comercial Safady Ltda. São Paulo, 1958. 568 páginas. Brochura.
História da Palestina nos tempos do Novo Testamento
Authors: Mehlmann João
Published: January 2018

Em 334 a. C. Alexandre Magno, levando consigo 32.000 soldados ,de infantaria e 5.000 de cavalaria, enceta sua campanha contra a Pérsia . A batalha do Grânico, ainda no mesmo ano, abre-lhe as 'portas de tôda a Ásia Menor, a de Issos, em 333, as da Mesopotâmia ao oriente, e as da Síria, da Fenícia, da Palestina e do Egito ao sul . Prefere conquistar 'em primeiro lugar as terras banhadas pelo Mediterrâneo, para anular a superioriade naval do inimigo. Desce, pois, ao sul, e toma a cidade de Tiro depois de um assédio de sete meses, assédio que fêz com que Tiro, de ilha que,era, ficasse daí em diante ligada à terra (1) . Gaza resiste dois meses. A visita de Alexandre a Jerusalém, de que fala Flávio José (A. 11, 8, 4 § 325- 5 §339). é provàvelmente invenção do espírito nacional judaico, empenhado em ligar de algum modo a capital e o templo iao gran-de conquistador (2) .
A expedição portuguesa ao Brasil em 1501-1502 e Amerigo Vespucci
Authors: Souza Thomaz Oscar Marcondes de
Published: January 2018

O único cronista português que dá notícia do envio, pelo rei D. Manuel, de uma expedição exploradora ao litoral brasileiro em 1501 é Antônio Gaivão, na sua obra publicada em Lisboa em 1563 sob o título: Tratado dos Descobrimentos.
O café e a industrialização da cidade de São Paulo
Authors: Cardoso Fernando Henrique
Published: January 2018

A afirmação de que o café é responsável pelo surto de industrialização de São Paulo é uma destas meio verdades que tém o dom de seduzir quantos pensem sôbre o problema, e logo tornou-se lugar comum na pena dos escritores que analisaram o processo de industrialização da cidade ou a expansão da lavoura cafeeira.