bluuebunny/crossref_metadata_2025 huggingface dataset:
Estudio normativo de la familiaridad subjetiva en niños de segundo grado de Educación Primaria en Medellín (Colombia)
Authors: Aristizábal Cataño Paula Alejandra , Muñetón Ayala Mercedes Amparo , Tamayo Pineda Estefanía
Published: September 2018

El objetivo de este estudio, consistió en evaluar la familiaridad subjetiva (FS) de 827 palabras en 187 niños de segundo grado de educación primaria de la ciudad de Medellín. Las palabras, fueron extraídas de diferentes textos escolares y se ajustaron a tres parámetros psicolingüísticos: consistencia ortográfica, estructura silábica y longitud. En la prueba realizada, los niños debían indicar si conocían nada, poco, mucho o muchísimo cada una de las palabras seleccionadas. De acuerdo con esto, se asignó un valor numérico a cada palabra. Un análisis estadístico de las medianas de las palabras, permitió seleccionar 405 palabras con FS alta y 422 palabras con FS baja. Los resultados, muestran que los parámetros psicolingüísticos propuestos se relacionan con la FS.
Tríada oscura de personalidad, satisfacción laboral y cinismo organizacional: un modelo estructural
Authors: Salessi Solana , Omar Alicia
Published: September 2018

Se analizó el impacto del cinismo organizacional sobre las relaciones entre la tríada oscura (maquiavelismo, narcisismo, psicopatía) y la satisfacción laboral, en una muestra de 343 trabajadores argentinos. Se plantearon hipótesis sobre relaciones directas e indirectas que fueron probadas mediante análisis de ecuaciones estructurales. Los resultados confirmaron que la tríada predice el cinismo (maquiavelismo: ϒ = 0.39, p < 0.01; psicopatía: ϒ = 0.22, p < 0.01; narcisismo: ϒ = 0.14; p < 0.05), y que el cinismo mediatiza completamente las relaciones entre la tríada y la satisfacción laboral (maquiavelismo: z = -4.51, p < 0.001; psicopatía: z = -3.24, p < 0.001; narcisismo: z = -1.78, p < 0.05). Se discuten las implicancias prácticas de los hallazgos y se sugieren nuevas líneas de investigación futura.
Staged excision of primary periocular basal cell carcinoma: absence of residual tumour in re-excised specimens: a 10-year series
Authors: McGrath Lindsay A , Meeney Adam , Currie Zanna I , Mudhar Hardeep Singh , Tan Jennifer H
Published: September 2018

Aims

The aim is to study staged periocular basal cell carcinoma (BCC) excision in a tertiary oculoplastic referral centre in Sheffield, UK. In particular, we examined patients with close or positive margins and no tumour seen on re-excision to identify demographics and tumour characteristics in this population.

Methods

A retrospective review of medical records of 437 cases of staged periocular BCC excisions over a 10-year period (2007–2017) was carried out. Patients had surgical excision with 3 mm clinically clear margins. Staged excision was performed for all cases included in this study. Standard reconstruction techniques were employed. Histopathology was analysed for tumour type, subtype and stage.

Results

Over the 10-year period, of the 437 periocular BCCs, 156 had close or involved margins. Residual tumour was found in 29 (18.6%), whereas in 122 eyelids of 120 patients (78.2%) no residual tumour was identified on histological examination. Micronodular (54.1%) and nodular (23.7%) growth patterns of BCC, as well as lower eyelid location (72.1%), were the most prevalent in this population. Two patients (1.6%) had recurrence of BCC over a mean follow-up of 57 months (range 1–125 months).

Conclusions

A significant proportion of BCCs transected on initial excision show no residual tumour in the re-excision specimens. In the interval between initial excision and re-excision, there may be eradication of the residual tumour. The exact mechanisms for this are unclear, however, and re-excision remains the appropriate recommended course in the presence of involved surgical margins of periocular BCC, particularly when high-risk tumour subtypes are encountered.
Clubfoot treatment in 2015: a global perspective
Authors: Owen Rosalind M , Capper Beth , Lavy Christopher
Published: September 2018

Introduction

Clubfoot affects around 174 000 children born annually, with approximately 90% of these in low-income and middle-income countries (LMIC). Untreated clubfoot causes life-long impairment, affecting individuals’ ability to walk and participate in society. The minimally invasive Ponseti treatment is highly effective and has grown in acceptance globally. The objective of this cross-sectional study is to quantify the numbers of countries providing services for clubfoot and children accessing these.

Method

In 2015–2016, expected cases of clubfoot were calculated for all countries, using an incidence rate of 1.24/1000 births. Informants were sought from all LMIC, and participants completed a standardised survey about services for clubfoot in their countries in 2015. Data collected were analysed using simple numerical analysis, country coverage levels, trends over time and by income group. Qualitative data were analysed thematically.

Results

Responses were received from 55 countries, in which 79% of all expected cases of clubfoot were born. More than 24 000 children with clubfoot were enrolled for Ponseti treatment in 2015. Coverage was less than 25% in the majority of countries. There were higher levels of response and coverage within the lowest income country group. 31 countries reported a national programme for clubfoot, with the majority provided through public–private partnerships.

Conclusion

This is the first study to describe global provision of, and access to, treatment services for children with clubfoot. The numbers of children accessing Ponseti treatment for clubfoot in LMIC has risen steadily since 2005. However, coverage remains low, and we estimate that less than 15% of children born with clubfoot in LMIC start treatment. More action to promote the rollout of national clubfoot programmes, build capacity for treatment and enable access and adherence to treatment in order to radically increase coverage and effectiveness is essential and urgent in order to prevent permanent disability caused by clubfoot.
Twenty-three year-old with pleuritic chest pain
Authors: Gopaul Karina P , Parry Helen M , Cullington Damien
Published: September 2018

Clinical introduction

A 23-year-old woman followed at another medical centre for congenital heart disease (CHD) presented to our emergency clinic with 3 weeks of bilateral pleuritic chest pain. She returned from holiday in Greece 6 weeks earlier where a tattoo and nasal piercing had been performed. There was no history of night sweats or fever.

Her temperature was 37.5°C, heart rate 120 beats/min, oxygen saturations 94% on room air and blood pressure 110/74. Her chest was clear and there was systolic murmur on auscultation. The chest radiograph showed peripheral bilateral lower zone atelectasis. The ECG demonstrated sinus tachycardia. The haemoglobin was 11.2 g/dL, white cell count 10.18×109/L, C-reactive protein 67 mg/L (normal <5 mg/L) and D dimer=430 ng/mL (normal <230 ng/mL).

A pulmonary embolus was suspected and a CT pulmonary angiogram was performed (figure 1).

Question

Based on the CT findings, what is the most likely underlying congenital heart lesion in this patient?

Bicuspid aortic valve

Coarctation of the aorta

Fontan circulation

Parachute mitral valve

Ventricular septal defect

Figure 1

CT pulmonary angiogram (coronal views).
Mortalities, amyloidosis and other diseases in free‐living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands
Authors: Blackett Tiffany Anne , Simpson Vic R , Haugland Sean , Everest David J , Muir Clare F , Smith Kenneth C , Mill Aileen C
Published: September 2018

Between 2007 and 2014, 337 free‐living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands, were examined post mortem as part of a mortality and disease surveillance scheme. Road traffic accidents (RTAs) were attributable for 50.7 per cent (171/337) of the casualties, 34.4 per cent (116/337) succumbed to diseases including fatal exudative dermatitis (FED), 7.1 per cent (24/337) to predation, 6.5 per cent (22/337) to other trauma and 1.2 per cent (4/337) to suspected poisoning. Cat predation accounted for 5 per cent (17/337) of mortalities. Pathologies were diverse and individual animals were often identified with more than one disease process. Squirrelpox virus (SQPV) particles were not detected in selected cases examined by transmission electron microscopy (TEM). Amyloid was identified in 19.3 per cent (65/337) of squirrels, often in conjunction with inflammatory lesions like hepatic capillariasis. A consistent cause of amyloid accumulation was not identified, although there was a significant association of amyloidosis with hepatic capillariasis and FED. In addition to RTAs, amyloidosis and FED have been identified as important causes of squirrel morbidity and mortality on Jersey, while the underlying aetiology and predisposing factors for these two disease complexes are presently unclear. Disease, fragmented woodlands, an increasingly suburban habitat, along with various anthropogenic factors, may jeopardise the long‐term viability of this island red squirrel population.
Critical Sequences and Resource Links Optimization in Resource-Constrained Project Scheduling
Authors: Cui Wan-An
Published: September 2018

In order to identify critical activities and critical sequences under resource availability constraints, resource dependencies need to be established. By doing this, project managers and practitioners can focus their limited energy on specific activities and paths during the execution of a project schedule, thus guaranteeing that the project gets finished on time and with the available resources. This study proposes various rules to judge the superiority or inferiority of the methods of dependencies’ creation. The total number of critical sequences which is one of these rules, directly influences the degree of difficulty in controlling the whole project — a major concern for project managers. This study classifies activities in a resource-constrained project schedule on the basis of the relationships between activities and develops the basic idea behind the optimization of resource dependencies. Specifically, two mathematical models to minimize the total number of critical sequences and that of resource links through the table translation method are proposed. A computation example shows great improvement in the number of critical sequences, critical activities and resource links and gives effective results while solving the problems in the previous research. Moreover, simulations using J30, J60, and J120 instances by Kolisch highlight the high computing speed when searching for the actual minimum number of critical sequences and resource links thanks to the table translation method.
An Auction Approach for Cost and Schedule Management of IT Outsourcing Project
Authors: Lu Fuqiang , Hu Yanli , Bi Hualing , Huang Min , Zhao Meng
Published: September 2018

Cost and schedule management are important issues in an information technology outsourcing project. Generally, a client does not know much about market quotation and ability of vendors. Thus, an efficient approach should select a suitable vendor for the project with balanced cost and schedule. In this study, an improved standard English auction (ISEA) is designed, in which the multi-attribute situation is considered, and multi-attribute utility theory (MAUT) is introduced. A new auction protocol and a utility increment function are proposed, respectively. Finally, numerical examples are designed to demonstrate the auction process and its operation. Some insights are found: The ISEA is competent to describe the cost and schedule management process in an auction approach. The optimal incremental utility for client and vendor are found, and the proposed auction protocol is a mechanism for the client and vendor to obtain win–win results. The completely consistent results can be obtained from different size cases, which indicates that the validity of the designed auction mechanism and the effect of the utility increase function on the negotiation results.
Konjac Glucomannan Derived Carbon Aerogels for Multifunctional Applications
Authors: Lian Jie , Li Jiwei , Wang Liang , Cheng Ru , Tian Xiuquan , Li Xue , Zhou Jian , Duan Tao , Zhu Wenkun
Published: September 2018

Environmental and energy issues have always been a hot topic of global research. Oil leakage has caused great damage to the environment, affecting a wide area and it is difficult to clean up. In most cases, carbon-based adsorbents are typically utilized to remove oil spills because of their economic benefits and high adsorbent efficiency. At the same time, its excellent material properties can also be used for the preparation of supercapacitors. In this paper, the carbon aerogels were prepared by the one-step method. The prepared materials endowed a 3D network structure with a huge number of micropores and mesoporous, and the material is light-weight, stable, hydrophobic and has affinity for oil (17.02[Formula: see text]g/g) to the KGM carbon aerogel. Through the physic-chemical characterization, the KGM carbon aerogel shows specific surface area is 689[Formula: see text]m2/g, high water contact angle (136.64[Formula: see text]) and excellent reusability (more than 15 cycle times). In addition, we also discussed the electrochemical properties of the material and obtained the specific electrical capacity of 139[Formula: see text]F/g under the condition of 1[Formula: see text]A/g.
Modeling Alzheimer’s Disease Progression with Fused Laplacian Sparse Group Lasso
Authors: Liu Xiaoli , Cao Peng , Gonçalves André R. , Zhao Dazhe , Banerjee Arindam
Published: September 2018

Alzheimer’s disease (AD), the most common type of dementia, not only imposes a huge financial burden on the health care system, but also a psychological and emotional burden on patients and their families. There is thus an urgent need to infer trajectories of cognitive performance over time and identify biomarkers predictive of the progression. In this article, we propose the multi-task learning with fused Laplacian sparse group lasso model, which can identify biomarkers closely related to cognitive measures due to its sparsity-inducing property, and model the disease progression with a general weighted (undirected) dependency graphs among the tasks. An efficient alternative directions method of multipliers based optimization algorithm is derived to solve the proposed non-smooth objective formulation. The effectiveness of the proposed model is demonstrated by its superior prediction performance over multiple state-of-the-art methods and accurate identification of compact sets of cognition-relevant imaging biomarkers that are consistent with prior medical studies.
Stability and Robustness in Influence Maximization
Authors: He Xinran , Kempe David
Published: September 2018

In the well-studied Influence Maximization problem, the goal is to identify a set of
k
nodes in a social network whose joint influence on the network is maximized. A large body of recent work has justified research on Influence Maximization models and algorithms with their potential to create societal or economic value. However, in order to live up to this potential, the algorithms must be robust to large amounts of noise, for they require quantitative estimates of the influence, which individuals exert on each other; ground truth for such quantities is inaccessible, and even decent estimates are very difficult to obtain.

We begin to address this concern formally. First, we exhibit simple inputs on which even very small estimation errors may mislead every algorithm into highly suboptimal solutions. Motivated by this observation, we propose the Perturbation Interval model as a framework to characterize the stability of Influence Maximization against noise in the inferred diffusion network. Analyzing the susceptibility of specific instances to estimation errors leads to a clean algorithmic question, which we term the Influence Difference Maximization problem. However, the objective function of Influence Difference Maximization is NP-hard to approximate within a factor of
O
(
n
1−ϵ)
for any ϵ > 0.

Given the infeasibility of diagnosing instability algorithmically, we focus on finding influential users robustly across multiple diffusion settings. We define a Robust Influence Maximization framework wherein an algorithm is presented with a set of influence functions. The algorithm’s goal is to identify a set of
k
nodes who are simultaneously influential for all influence functions, compared to the (function-specific) optimum solutions. We show strong approximation hardness results for this problem unless the algorithm gets to select at least a logarithmic factor more seeds than the optimum solution. However, when enough extra seeds may be selected, we show that techniques of Krause et al. can be used to approximate the optimum robust influence to within a factor of 1−1/
e
. We evaluate this bicriteria approximation algorithm against natural heuristics on several real-world datasets. Our experiments indicate that the worst-case hardness does not necessarily translate into bad performance on real-world datasets; all algorithms perform fairly well.
Report on the 2nd International Workshop on Recent Trends in News Information Retrieval (NewsIR'18)
Authors: Albakour1 Dyaa , Corney David , Gonzalo Julio , Martinez1 Miguel , Poblete Barbara , Vlachos Andreas
Published: September 2018

The news industry has undergone a revolution in the past decade, with substantial changes continuing to this day. News consumption habits are changing due to the increase in the volume of news and the variety of sources. Readers need new mechanisms to cope with this vast volume of information in order to not only find a signal in the noise, but also to understand what is happening in the world given the multiple points of view describing events. These challenges in journalism relate to Information Retrieval (IR) and Natural Language Processing (NLP) fields such as: verification of a source's reliability; the integration of news with other sources of information; real-time processing of both news content and social streams; de-duplication of stories; and entity detection and disambiguation. Although IR and NLP have been applied to news for decades, the changing nature of the space requires fresh approaches and a closer collaboration with our colleagues from the journalism environment. Following the success of the previous version of the workshop (NewsIR'16), the goal of this workshop, held in conjunction with ECIR 2018, is to continue to stimulate such discussion between the communities and to share interesting approaches to solve real user problems. A total number of 19 submissions were received and reviewed, of which 12 were accepted for presentation. In addition to that, we had over 30 registered participants in the workshop who were pleased to attend the two keynote talks given by well-known experts in the field - Edgar Meij (from industry) and Peter Tolmie (from academia) and oral and poster presentations from the accepted papers. The workshop also included a breakout session to discuss ideas for a future data challenge in news IR and closed with a focused panel discussion to reflect on the day. In summary, several ideas were presented in the workshop on solving complex information needs in the news domain. In addition, the workshop concluded with suggestions of important challenges and shared tasks to work on as a community for News IR.
ECIR 2018
Authors: Jorge Alípio , Campos Ricardo , Jatowt Adam , Nunes Sérgio , Rocha Conceição , Cordeiro João Paulo , Pasquali Arian , Mangaravite Vitor
Published: September 2018

The 1st International Workshop on Narrative Extraction from Texts (Text2Story 2018) was held in conjunction with the 40th European Conference on Information Retrieval, ECIR 2018, Grenoble on the 26 th March 2018. The workshop aimed to help foster the collaboration of researchers on a wide range of multidisciplinary issues related to the text-to-narrativestructure. The program consisted of two keynote talks, six research presentations, a poster session and a slot for demo presentations. This report briefly summarizes the workshop. More information about the workshop is available at http://text2story18.inesctec.pt
Approaches for Enriching and Improving Textual Knowledge Bases
Authors: Fetahu Besnik
Published: September 2018

Verifiability is one of the core editing principles in Wikipedia, where editors are encouraged to provide citations for the added statements. Statements can be any arbitrary piece of text, ranging from a sentence up to a paragraph. However, in many cases, citations are either outdated, missing, or link to non-existing references (e.g. dead URL, moved content etc.). In total, 20% of the cases such citations refer to news articles and represent the second most cited source. Even in cases where citations are provided, there are no explicit indicators for the span of a citation for a given piece of text. In addition to issues related with the verifiability principle, many Wikipedia entity pages are incomplete, with relevant information that is already available in online news sources missing. Even for the already existing citations, there is often a delay between the news publication time and the reference time. In this thesis, we address the aforementioned issues and propose automated approaches that enforce the verifiability principle in Wikipedia, and suggest relevant and missing news references for further enriching Wikipedia entity pages. To this end we make the following contributions as part of this thesis [1, 2, 3, 4]
Mutual Coupling Reduction Using a Protruded Ground Branch Structure in a Compact UWB Owl-Shaped MIMO Antenna
Authors: Mchbal A. , Amar Touhami N. , Elftouh H. , Dkiouak A.
Published: September 2018

A compact ultra-wideband (UWB) multiple input-multiple output (MIMO) antenna with high isolation is designed for UWB applications. The proposed MIMO antenna consists of two identical monopole antenna elements. To enhance the impedance matching, three slots are formed on the ground plane. The arc structure as well as the semicircle with an open-end slot is employed on the radiating elements the fact which helps to extend the impedance bandwidth of the monopole antenna from 3.1 up to 10.6 GHz, which corresponds to the UWB band. A ground branch decoupling structure is introduced between the two elements to reduce the mutual coupling. Simulation and measurement results show a bandwidth range from 3.1 to 11.12 GHz with |S11_|<−15 dB, |S21_|<−20 dB, and ECC < 0.002.
Common DNA Variants Accurately Rank an Individual of Extreme Height
Authors: Sexton Corinne E. , Ebbert Mark T. W. , Miller Ryan H. , Ferrel Meganne , Tschanz Jo Ann T. , Corcoran Christopher D. , Alzheimer’s Disease Neuroimaging Initiative  , Ridge Perry G. , Kauwe John S. K.
Published: September 2018

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.
Epidemiological and Clinical-Pathological Aspects of Helicobacter pylori Infection in Brazilian Children and Adults
Authors: Toscano Evelyn Pedroso , Madeira Fernanda Fernandes , Dutra-Rulli Mayra Pinheiro , Gonçalves Luiz Otavio Maia , Proença Marcela Alcântara , Borghi Viviane Silva , Cadamuro Aline Cristina Targa , Mazzale Giselda Warick , Acayaba Ricardo , Silva Ana Elizabete
Published: September 2018

Aim. To evaluate the prevalence and risk factors of H. pylori infection in the pediatric and adult population seen at a public hospital in São José do Rio Preto, SP, Brazil. Methods. This is a retrospective study that evaluated 2406 medical records of children, adolescents, and adults with dyspeptic symptoms who underwent upper gastrointestinal endoscopy. H. pylori diagnosis and demographic and clinical-pathological features were recorded. Results. A total of 852 subjects were H. pylori positive, with an overall prevalence of infection of 35.4%, occurring mainly in adults over 40 years of age, and a 24.7% prevalence considering only children and adolescents. No association was observed between H. pylori infection and risk factors. However, the H. pylori positive individuals showed a higher frequency of pangastritis (p<0.01), severe lesions (p=<0.001), and erosive lesions (p=0.04). The bacterium was eradicated in 83.5% (127) of the patients who received the standard therapy. Conclusions. The prevalence of H. pylori detected in a public service in São José do Rio Preto, SP, Brazil, is as expected for developed countries, showing growing rates with increasing age. As H. pylori infection occurs during childhood, screening programs for detection and prevention in the pediatric population are important to reduce the prevalence of this infection in adults.
STAT3-Inducible Mouse ESCs: A Model to Study the Role of STAT3 in ESC Maintenance and Lineage Differentiation
Authors: Wong Yu Qian , Xu Hongyan , Wu Qiang , Liu Xinyu , Lufei Chengchen , Xu Xiu Qin , Fu Xin-Yuan
Published: September 2018

Studies have demonstrated that STAT3 is essential in maintaining self-renewal of embryonic stem cells (ESCs) and modulates ESC differentiation. However, there is still lack of direct evidence on STAT3 functions in ESCs and embryogenesis because constitutive STAT3 knockout (KO) mouse is embryonic lethal at E6.5–E7.5, prior to potential functional role in early development can be assessed. Therefore, in this study, two inducible STAT3 ESC lines were established, including the STAT3 knockout (InSTAT3 KO) and pSTAT3 overexpressed (InSTAT3 CA) using Tet-on inducible system in which STAT3 expression can be strictly controlled by doxycycline (Dox) stimulation. Through genotyping, deletion of STAT3 alleles was detected in InSTAT3 KO ESCs following 24 hours Dox stimulation. Western blot also showed that pSTAT3 and STAT3 protein levels were significantly reduced in InSTAT3 KO ESCs while dominantly elevated in InSTAT3 CA ECSs upon Dox stimulation. Likewise, it was found that STAT3-null ESCs would affect the differentiation of ESCs into mesoderm and cardiac lineage. Taken together, the findings of this study indicated that InSTAT3 KO and InSTAT3 CA ESCs could provide a new tool to clarify the direct targets of STAT3 and its role in ESC maintenance, which will facilitate the elaboration of the mechanisms whereby STAT3 maintains ESC pluripotency and regulates ESC differentiation during mammalian embryogenesis.
Abnormal Behavior Detection to Identify Infected Systems Using the APChain Algorithm and Behavioral Profiling
Authors: Seo Jungwoo , Lee Sangjin
Published: September 2018

Recent cyber-attacks have used unknown malicious code or advanced attack techniques, such as zero-day attacks, making them extremely difficult to detect using traditional intrusion detection systems. Botnet attacks, for example, are a very sophisticated type of cyber-security threat. Malicious code or vulnerabilities are used to infect endpoints. Systems infected with this malicious code connect a communications channel to a command and control (C&C) server and receive commands to perform attacks on target servers. To effectively protect a corporate network’s resources against such threats, we must be able to detect infected systems before an attack occurs. In this paper, an attack pattern chain algorithm (APChain) is proposed to identify infected systems in real-time network environments, and a methodology for detecting abnormal behavior through network-based behavioral profiling is explained. APChain analyzes the attribute information of real-time network traffic, connects chains over time, and conducts behavioral profiling of different attack types to detect abnormal behavior. The dataset used in the experiment employed real-time traffic accumulated over a period of six months, and the proposed algorithm was developed into a prototype for the experiment. The C&C channel detection accuracy was measured at 0.996, the true positive rate at 1.0, and the false positive rate at 0.003. This study proposes a methodology that can overcome the limitations of conventional security mechanisms and suggests an approach to the detection of abnormal behavior in a real-time network environment.
Astrocyte Elevated Gene-1 Regulates Macrophage Activation in Hepatocellular Carcinogenesis
Authors: Robertson Chadia L. , Mendoza Rachel G. , Jariwala Nidhi , Dozmorov Mikhail , Mukhopadhyay Nitai D. , Subler Mark A. , Windle Jolene J. , Lai Zhao , Fisher Paul B. , Ghosh Shobha , Sarkar Devanand
Published: September 2018

Chronic inflammation is a known hallmark of cancer and is central to the onset and progression of hepatocellular carcinoma (HCC). Hepatic macrophages play a critical role in the inflammatory process leading to HCC. The oncogene Astrocyte elevated gene-1 (AEG-1) regulates NFκB activation, and germline knockout of AEG-1 in mice (AEG-1−/−) results in resistance to inflammation and experimental HCC. In this study, we developed conditional hepatocyte- and myeloid cell–specific AEG-1−/− mice (AEG-1ΔHEP and AEG-1ΔMAC, respectively) and induced HCC by treatment with N-nitrosodiethylamine (DEN) and phenobarbital (PB). AEG-1ΔHEP mice exhibited a significant reduction in disease severity compared with control littermates, while AEG-1ΔMAC mice were profoundly resistant. In vitro, AEG-1−/− hepatocytes exhibited increased sensitivity to stress and senescence. Notably, AEG-1−/− macrophages were resistant to either M1 or M2 differentiation with significant inhibition in migration, endothelial adhesion, and efferocytosis activity, indicating that AEG-1 ablation renders macrophages functionally anergic. These results unravel a central role of AEG-1 in regulating macrophage activation and indicate that AEG-1 is required in both tumor cells and tumor microenvironment to stimulate hepatocarcinogenesis.

Significance: These findings distinguish a novel role of macrophage-derived oncogene AEG-1 from hepatocellular AEG-1 in promoting inflammation and driving tumorigenesis. Cancer Res; 78(22); 6436–46. ©2018 AACR.
A Randomized Trial to Compare a Tailored Web-Based Intervention and Tailored Phone Counseling to Usual Care for Increasing Colorectal Cancer Screening
Authors: Champion Victoria L. , Christy Shannon M. , Rakowski William , Gathirua-Mwangi Wambui G. , Tarver Will L. , Carter-Harris Lisa , Cohee Andrea A. , Marley Andrew R. , Jessup Nenette M. , Biederman Erika , Kettler Carla D. , Stump Timothy E. , Monahan Patrick , Lairson David R. , Rawl Susan M.
Published: September 2018

Background:

Colorectal cancer mortality could be decreased with risk-appropriate cancer screening. We examined the efficacy of three tailored interventions compared with usual care for increasing screening adherence.

Methods:

Women (n = 1,196) ages 51 to 74, from primary care networks and nonadherent to colorectal cancer guidelines, were randomized to (1) usual care, (2) tailored Web intervention, (3) tailored phone intervention, or (4) tailored Web + phone intervention. Average-risk women could select either stool test or colonoscopy, whereas women considered at higher than average risk received an intervention that supported colonoscopy. Outcome data were collected at 6 months by self-report, followed by medical record confirmation (attrition of 23%). Stage of change for colorectal cancer screening (precontemplation or contemplation) was assessed at baseline and 6 months.

Results:

The phone (41.7%, P < 0.0001) and combined Web + phone (35.8%, P < 0.001) interventions significantly increased colorectal cancer screening by stool test compared with usual care (11.1%), with ORs ranging from 5.4 to 6.8 in models adjusted for covariates. Colonoscopy completion did not differ between groups except that phone significantly increased colonoscopy completion compared with usual care for participants in the highest tertile of self-reported fear of cancer.

Conclusions:

A tailored phone with or without a Web component significantly increased colorectal cancer screening compared with usual care, primarily through stool testing, and phone significantly increased colonoscopy compared with usual care but only among those with the highest levels of baseline fear.

Impact:

This study supports tailored phone counseling with or without a Web program for increasing colorectal cancer screening in average-risk women.
Classes of ITD Predict Outcomes in AML Patients Treated with FLT3 Inhibitors
Authors: Schwartz Gregory W. , Manning Bryan , Zhou Yeqiao , Velu Priya , Bigdeli Ashkan , Astles Rachel , Lehman Anne W. , Morrissette Jennifer J.D. , Perl Alexander E. , Li Mingyao , Carroll Martin , Faryabi Robert B.
Published: September 2018

Purpose:

Recurrent internal tandem duplication (ITD) mutations are observed in various cancers including acute myeloid leukemia (AML), where ITD mutations in tyrosine kinase receptor FLT3 are associated with poor prognostic outcomes. Several FLT3 inhibitors (FLT3i) are in clinical trials for high-risk FLT3-ITD–positive AML. However, the variability of survival following FLT3i treatment suggests that the mere presence of FLT3-ITD mutations might not guarantee effective clinical response. Motivated by the heterogeneity of FLT3-ITD mutations, we investigated the effects of FLT3-ITD structural features on the response of AML patients to treatment.

Experimental Design: We developed the HeatITup (HEAT diffusion for Internal Tandem dUPlication) algorithm to identify and quantitate ITD structural features including nucleotide composition. Using HeatITup, we studied the impact of ITD structural features on the clinical response to FLT3i and induction chemotherapy in FLT3-ITD–positive AML patients.

Results:

HeatITup accurately identifies and classifies ITDs into newly defined categories of “typical” or “atypical” based on their nucleotide composition. A typical ITD's insert sequence completely matches the wild-type FLT3, whereas an atypical ITD's insert contains nucleotides exogenous to the wild-type FLT3. Our analysis shows marked divergence between typical and atypical ITD mutation features. Furthermore, our data suggest that AML patients carrying typical FLT3-ITDs benefited significantly more from both FLT3i and induction chemotherapy treatments than patients with atypical FLT3-ITDs.

Conclusions:

These results underscore the importance of structural discernment of complex somatic mutations such as ITDs in progressing toward personalized treatment of AML patients, and enable researchers and clinicians to unravel ITD complexity using the provided software.

See related commentary by Gallipoli and Huntly, p. 460
T Cell–Inflamed versus Non-T Cell–Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection
Authors: Trujillo Jonathan A. , Sweis Randy F. , Bao Riyue , Luke Jason J.
Published: September 2018

Immunotherapies such as checkpoint-blocking antibodies and adoptive cell transfer are emerging as treatments for a growing number of cancers. Despite clinical activity of immunotherapies across a range of cancer types, the majority of patients fail to respond to these treatments and resistance mechanisms remain incompletely defined. Responses to immunotherapy preferentially occur in tumors with a preexisting antitumor T-cell response that can most robustly be measured via expression of dendritic cell and CD8+ T cell–associated genes. The tumor subset with high expression of this signature has been described as the T cell–“inflamed” phenotype. Segregating tumors by expression of the inflamed signature may help predict immunotherapy responsiveness. Understanding mechanisms of resistance in both the T cell–inflamed and noninflamed subsets of tumors will be critical in overcoming treatment failure and expanding the proportion of patients responding to current immunotherapies. To maximize the impact of immunotherapy drug development, pretreatment stratification of targets associated with either the T cell–inflamed or noninflamed tumor microenvironment should be employed. Similarly, biomarkers predictive of responsiveness to specific immunomodulatory therapies should guide therapy selection in a growing landscape of treatment options. Combination strategies may ultimately require converting non-T cell–inflamed tumors into T cell–inflamed tumors as a means to sensitize tumors to therapies dependent on T-cell killing. Cancer Immunol Res; 6(9); 990–1000. ©2018 AACR.
Risk Analysis of Colorectal Post-Polypectomy Bleeding Due to Antithrombotic Agent
Authors: Kishida Yoshihiro , Hotta Kinichi , Imai Kenichiro , Ito Sayo , Yoshida Masao , Kawata Noboru , Tanaka Masaki , Kakushima Naomi , Takizawa Kohei , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki
Published: September 2018

Background/Aims: Post-polypectomy bleeding (PPB) is a major complication of colorectal polypectomy, and antithrombotics is one of the major risk factors of PPB. The purpose of this study was to investigate PPB risks with regard to the combinations of antithrombotic agents used. Methods: We retrospectively reviewed cases involving colonoscopic polyp resection between September 2002 and December 2014. The risk of PPB was assessed according to patient and lesion factors, including antithrombotic use. Antithrombotics were discontinued before polypectomy. Results: A total of 6,382 colonoscopies with 12,876 polypectomies were analyzed. PPB occurred in 55 patients (0.9%) and 63 lesions (0.5%). Among patients treated with antithrombotics, heparin bridging (HB) therapy was an independent risk factor of PPB (per patient, 20%, OR 33.1, p < 0.001; per lesion, 9.1%, OR 17.3, p < 0.001) compared to those without antithrombotics (per patient 0.7%; per lesion 0.4%). Among patients without HB, the combination of anticoagulant + antiplatelet agents was significantly associated with PPB (per patient, 5%, OR 7.73, p = 0.007; per lesion, 2.4%, OR 6.31, p = 0.003). Conclusion: HB therapy is a major risk factor for PPB. Among patients without HB, anticoagulant + antiplatelet therapy was a significant risk factor for PPB.
Influence of Relative Humidity on Electrodermal Levels and Responses
Authors: Bari Dindar S. , Aldosky Haval Y. Yacoob  , Tronstad Christian  , Kalvøy  Håvard  , Martinsen Ørjan G.
Published: September 2018

Background/Aim: Electrodermal activity (EDA) is a widely used measure in psychophysiological research, and its use in wearable devices has grown in recent times. It is recommended to have proper conditions for EDA measurement, and skin hydration is one factor that has a significant influence. It is, however, not known to what extent the ambient humidity influences the recording. This study explored the influence of relative humidity (RH) on EDA levels, and also the responses using a new technique for simultaneous recording of all measures of EDA: skin conductance (SC), skin susceptance (SS), and skin potential (SP) at the same skin site. Methods: A total of 10 healthy subjects were exposed to environments of low and high RH while EDA measures were recorded, including cognitive, visual and breathing stimuli for evoking electrodermal responses of different origin. EDA levels and responses were compared between the two humidity levels for all stimuli and all EDA measures. Results: It was found that EDA levels, in particular for SC and SS, were significantly increased during high humidity exposure, but that the change in EDA responses (SC, SS, and SP) was not statistically significant (p > 0.05, paired t test). Conclusion: This suggests that ambient humidity influences the recording of EDA levels and is important to consider when these parameters are used, but is not important in the recording or analysis of EDA responses.
ІНТЕНСИВНІСТЬ ФІБРОЗОУТВОРЕННЯ В ПЕЧІНЦІ ХВОРИХ НА НЕАЛКОГОЛЬНИЙ СТЕАТОГЕПАТИТ НА ТЛІ ОЖИРІННЯ І–ІІ СТУПЕНІВ ТА ХРОНІЧНУ ХВОРОБУ НИРОК
Authors: Khuchlina O. S. , Antoniv A. A. , Kuzminska O. B. , Liakhovych O. D. , Mandryk O. Je.
Published: September 2018

Мета роботи – дослідити біохімічні маркери фіброзу печінки при НАСГ, що розвинувся на тлі ожиріння І–ІІ ступенів та ХХН І–ІІІ стадій.Матеріал і методи. Обстежено 98 хворих на НАСГ на тлі ожиріння І–ІІ ступенів, у тому числі 52 хворих на НАСГ на тлі ожиріння І–ІІ ступенів (1 група) без супровідної ХХН, 46 хворих на НАСГ на тлі ожиріння І–ІІ ступенів із коморбідною ХХН І–ІІІ ст. (2 група). Контрольну групу склали 20 практично здорових осіб (ПЗО) відповідного віку та статі.Визначення структурних змін паренхіми печінки та нирок здійснювали шляхом проведення ультрасонографічного (УСГ) дослідження. З метою кількісної оцінки змін ехогенності печінки використали метод еходенситомет­рії із обчисленням гепаторенального індексу (ГРІ). Біопсія печінки виконана 32 хворим на НАСГ із супровідною ХХН І–ІІІ ст., 28 хворим на НАСГ без ХХН. Біоптати печінки отримували шляхом черезшкірної чи лапароскопічної прицільної біопсії.Результати. Встановлено, що коморбідний перебіг НАСГ із ХХН характеризується вищим ступенем стеатозу печінки (ГРІ у 1,3 раза вищий, порівняно з групою хворих на НАСГ (p<0,05)), та вищим діагностичним порогом значень гепаторенального індексу, який у сильній взаємозалежності корелює зі ступенем стеатозу печінки, визначеним за Steato-test (r=0,87; p<0,001).При неалкогольному стеатогепатиті, що розвивається на тлі ожиріння та ХХН І–ІІІ стадії, встановлено наявність у печінковій тканині фібротичних змін, які за біохімічним індексом фіброзу перевищують такі у хворих на НАСГ без коморбідності з патологією нирок. При НАСГ встановлено прояви переважно F0–F1 cтадій фіброзу печінки, при НАСГ із супровідною ХХН І–ІІІ стадії переважали F1–F2 стадії фіброзу печінкової тканини.Висновки. У хворих на НАСГ на тлі ожиріння найчастіше спостерігали перицелюлярний фіброз (у 100 % випадків), дещо рідше зустрічали фіброз перисинусоїдально типу (39,3 %) та центролобулярний (35,7 %) і у 10,7 % спостерігали перипортальний та портальний фіброз печінки. У хворих на НАСГ на тлі ожиріння та ХХН І–ІІІ ст. перицелюлярний фіброз також виявляли у 100 % випадків, значний відсоток займали перисинусоїдальний (78,1 %) та перивенулярний (68,8 %) фіброз 3-ї зони, а також фіброз портального та/або перипортального типу з поодинокими септами (25,0 %).
АНАЛІЗ ДІЄВОСТІ ПРОГРАМИ РЕАБІЛІТАЦІЇ ХВОРИХ НА ХРОНІЧНИЙ ПАНКРЕАТИТ ІЗ СУПУТНЬОЮ АНЕМІЄЮ НА АМБУЛАТОРНОМУ РІВНІ ДОПОМОГИ
Authors: Palyhata M. V. , Babinets L. S. , Sabat Z. I. , Borovyk I. O.
Published: September 2018

Актуальною на сьогодні є проблема поширення полідефіцитної анемії, яка зумовлена тим, що нестача вмісту заліза в організмі, як правило, асоціюється з дефіцитом міді, цинку, кобальту, марганцю, білка, вітамінів В і С, роль яких безпосередньо пов’язана з обміном заліза. Саме тому додатково до схеми загального лікування було запропоновано призначати комплексний залізовмісний полімінерально-вітамінний препарат по 1 капсулі двічі на день протягом місяця двічі на рік в якості реабілітаційних заходів.Мета – провести порівняльний аналіз параметрів обміну заліза у пацієнтів з ХП у поєднанні із ЗДА у ході загальноприйнятого лікування і програми терапії з використанням комплексного залізовмісного полімінерально-вітамінного препарату Ферсінол-Z.Матеріал і методи. Було проаналізовано схеми лікування 29 обстежених хворих на ХП із супутньою анемією, які отримували лікування на базі гастроентерологічного відділення КНП “ТКМЛ № 2".Результати. Встановили позитивну динаміку досліджуваних показників обміну заліза після лікування, порів­няно з такими до лікування: рівень RBC збільшився на 14,28 %, HGB – на 12,36 %, КП – на 3,49 %, HCT – на 26,69 %, MCV – на 9,45 %, ЗС – на 40,63 %, НТЗ – на 55,10 %, ЗЗЗС і ЛЗЗС зменшилися на 9,33 % і 19,11 % відповідно (p<0,05). Рівні MCV і HCT нормалізувалися, що свідчило про повну елімінацію мікроцитозу еритроцитів. Рівень ЛЗЗС також нормалізувався, що свідчило про поповнення депо заліза. Прийом препарату зумовив зменшення кількості реци­дивів (загострень) ХП залежно від тяжкості клінічного перебігу хвороби: у пацієнтів із легким перебігом – з (1,48±0,15) до (0,68±0,1), із середнім ступенем тяжкості – з (2,32±0,17) до (1,87±0,19) і з тяжким – з (4,11±0,31) до (3,18±0,37).Висновки. Включення комплексного залізовмісного полімінерально-вітамінного препарату Ферсінол-Z до програми комплексної реабілітації хворих на хронічний панкреатит із супутньою ЗДА привело до покращення лабораторних параметрів обміну заліза, а також до зменшення кількості рецидивів ХП, що довело дієвість запро­по­нованого курсу реабілітації за впливом на клінічний перебіг ХП із супутньою анемією.
ВПЛИВ АЦЕТАТУ СВИНЦЮ ТА СТЕАРАТІВ НАТРІЮ І КАЛІЮ НА ПОКАЗНИКИ ПЕРИФЕРІЙНОЇ КРОВІ ПІДДОСЛІДНИХ ТВАРИН
Authors: Fedoriv O. Ye. , Kopach O. Ye. , Melnyk N. A.
Published: September 2018

Однією із найтоксичніших для людського організму речовин є свинець та його сполуки. Сполуки свинцю, що потрапляють зі стічними водами у водойми, можуть контактувати з поверхнево-активними речовинами (ПАР), типу стеаратів натрію і калію, та здатні впливати як на токсичність, так і на проникність важких металів в організм теплокровних тварин.Мета – вивчити вплив ацетату свинцю в комбінації зі стеаратами натрію і калію на показники периферійної крові піддослідних тварин.Матеріал і методи. Було проведено досліди на 4 групах білих щурів, яким перорально вводили ацетат свинцю на фоні споживання тваринами вод із вмістом стеаратів натрію та калію. Після 40-денного вживання цих вод тваринам перорально вводили ацетат свинцю, а через три доби робили мазки крові.Результати. При комбінованому надходженні сполук свинцю в організм піддослідних тварин відмічалося збільшення кількості паличкоядерних нейтрофілів та еозинофілів і, водночас, зменшення сегментоядерних нейтрофілів.Висновок. Встановлено, що при комбінованій дії ацетату свинцю в поєднанні зі стеаратами у крові піддослідних тварин збільшується кількість паличкоядерних нейтрофілів і еозинофілів, порівняно з контролем, та зменшується кількість сегментоядерних нейтрофілів.