bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myosin 1f is specifically required for neutrophil migration in 3D environments during acute inflammation
Authors: Salvermoser Melanie , Pick Robert , Weckbach Ludwig T. , Zehrer Annette , Löhr Phillip , Drechsler Maik , Sperandio Markus , Soehnlein Oliver , Walzog Barbara 
Published: February 2018

Key Points
Myo1f is critical for migration in 3D environments. Myo1f regulates the dynamic deformation of the nucleus during migration through physical barriers.
The interplay of leukemia cells and the bone marrow microenvironment
Authors: Duarte Delfim , Hawkins Edwin D. , Lo Celso Cristina 
Published: February 2018

Abstract
The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models has advanced our comprehension of leukemia-microenvironment crosstalk and has potential implications for development of novel treatment options.
VIM-positive Pseudomonas aeruginosa in a large tertiary care hospital: matched case-control studies and a network analysis
Authors: Voor in ‘t holt Anne F. , Severin Juliëtte A. , Hagenaars Margot B. H. , de Goeij Inge , Gommers Diederik , Vos Margreet C. 
Published: February 2018

Abstract
Background
Emergence of multidrug-resistant Pseudomonas aeruginosa is of global concern. We aimed to identify epidemiological relationships, the most common way of transmission, and risk factors for presence of Verona Integron-encoded Metallo-β-lactamase (VIM)-positive P. aeruginosa (VIM-PA).

Methods
We conducted a network analysis and matched case-control studies (1:2:2). Controls were hospital-based and matched with cases for ward, day of admission (control group 1 and 2) and time between admission and the identification of VIM-PA (control group 1). The network was visualized using Cytoscape, and risk factors were determined using conditional logistic regression.

Results
Between August 2003 and April 2015, 144 case patients and 576 control patients were recruited. We identified 307 relationships in 114 out of these 144 patients, with most relationships (84.7%) identified at the same department < 3 months after a previous case patient was discharged. In the multivariable model, having undergone ≥1 gastroscopy (odds ratio [OR] = 4.40, 95% confidence interval [CI] = 2.00 to 9.65 and OR = 2.47; 95% CI = 1.12 to 5.49), > 10 day use of selective digestive tract decontamination (SDD) (OR = 2.97; 95% CI = 1.02 to 8.68 and OR = 4.61; 95% CI = 1.22 to 17.37), and use of quinolones (OR = 3.29; 95% CI = 1.34 to 8.10 and OR = 3.95; 95% CI = 1.13 to 13.83 and OR = 4.47; 95% CI = 1.75 to 11.43) were identified as risk factors when using both control groups.

Conclusions
The network analysis indicated that the majority of transmissions occurred on the wards, but through unidentified and presumably persistent sources, which are most likely in the innate hospital environment. Previous use of certain antibiotic regimens made patients prone to VIM-PA carriage. Additionally, gastroscopy could be considered as a high-risk procedure in patients with risk factors. Our results add to the growing body of evidence that infection control measures targeting VIM-PA should be focused on reducing antibiotics and eliminating sources in the environment.
Gastroenteropancreatic neuroendocrine neoplasms: genes, therapies and models
Authors: Kawasaki Kenta , Fujii Masayuki , Sato Toshiro 
Published: February 2018

ABSTRACT
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) refer to a group of heterogeneous cancers of neuroendocrine cell phenotype that mainly fall into one of two subtypes: gastroenteropancreatic neuroendocrine tumors (GEP-NETs; well differentiated) or gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs; poorly differentiated). Although originally defined as orphan cancers, their steadily increasing incidence highlights the need to better understand their etiology. Accumulating epidemiological and clinical data have shed light on the pathological characteristics of these diseases. However, the relatively low number of patients has hampered conducting large-scale clinical trials and hence the development of novel treatment strategies. To overcome this limitation, tractable disease models that faithfully reflect clinical features of these diseases are needed. In this Review, we summarize the current understanding of the genetics and biology of these diseases based on conventional disease models, such as genetically engineered mouse models (GEMMs) and cell lines, and discuss the phenotypic differences between the models and affected humans. We also highlight the emerging disease models derived from human clinical samples, including patient-derived xenograft models and organoids, which may provide biological and therapeutic insights into GEP-NENs.
Use of zebrafish to study Shigella infection
Authors: Duggan Gina M. , Mostowy Serge 
Published: February 2018

ABSTRACT
Shigella is a leading cause of dysentery worldwide, responsible for up to 165 million cases of shigellosis each year. Shigella is also recognised as an exceptional model pathogen to study key issues in cell biology and innate immunity. Several infection models have been useful to explore Shigella biology; however, we still lack information regarding the events taking place during the Shigella infection process in vivo. Here, we discuss a selection of mechanistic insights recently gained from studying Shigella infection of zebrafish (Danio rerio), with a focus on cytoskeleton rearrangements and cellular immunity. We also discuss how infection of zebrafish can be used to investigate new concepts underlying infection control, including emergency granulopoiesis and the use of predatory bacteria to combat antimicrobial resistance. Collectively, these insights illustrate how Shigella infection of zebrafish can provide fundamental advances in our understanding of bacterial pathogenesis and vertebrate host defence. This information should also provide vital clues for the discovery of new therapeutic strategies against infectious disease in humans.
Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy
Authors: Prajapati Chandra , Ojala Marisa , Aalto-Setälä Katriina 
Published: February 2018

ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general.
Predicting ionizing radiation exposure using biochemically-inspired genomic machine learning
Authors: Zhao Jonathan Z.L. , Mucaki Eliseos J. , Rogan Peter K. 
Published: February 2018

Background: Gene signatures derived from transcriptomic data using machine learning methods have shown promise for biodosimetry testing. These signatures may not be sufficiently robust for large scale testing, as their performance has not been adequately validated on external, independent datasets. The present study develops human and murine signatures with biochemically-inspired machine learning that are strictly validated using k-fold and traditional approaches. Methods: Gene Expression Omnibus (GEO) datasets of exposed human and murine lymphocytes were preprocessed via nearest neighbor imputation and expression of genes implicated in the literature to be responsive to radiation exposure (n=998) were then ranked by Minimum Redundancy Maximum Relevance (mRMR). Optimal signatures were derived by backward, complete, and forward sequential feature selection using Support Vector Machines (SVM), and validated using k-fold or traditional validation on independent datasets. Results: The best human signatures we derived exhibit k-fold validation accuracies of up to 98% (DDB2, PRKDC, TPP2, PTPRE, and GADD45A) when validated over 209 samples and traditional validation accuracies of up to 92% (DDB2, CD8A, TALDO1, PCNA, EIF4G2, LCN2, CDKN1A, PRKCH, ENO1, and PPM1D) when validated over 85 samples. Some human signatures are specific enough to differentiate between chemotherapy and radiotherapy. Certain multi-class murine signatures have sufficient granularity in dose estimation to inform eligibility for cytokine therapy (assuming these signatures could be translated to humans). We compiled a list of the most frequently appearing genes in the top 20 human and mouse signatures. More frequently appearing genes among an ensemble of signatures may indicate greater impact of these genes on the performance of individual signatures. Several genes in the signatures we derived are present in previously proposed signatures. Conclusions: Gene signatures for ionizing radiation exposure derived by machine learning have low error rates in externally validated, independent datasets, and exhibit high specificity and granularity for dose estimation.
Serviço Social em Portugal no fascismo: oposição, resistência e ação sindical
Authors: Martins Alcina 
Published: February 2018

Resumo – Partilha-se a concepção de que o Serviço Social, enquanto profissão, é indissociável do desenvolvimento das relações sociais capitalistas, não se constituindo num bloco homogêneo. Na senda de Netto, os projectos societários em disputa pela manutenção ou transformação das estruturas sociais vigentes têm expressão nos projectos profissionais. Desse modo, com este trabalho procura-se contribuir para a análise da construção do Serviço Social em Portugal, apreendendo o significado atribuído pelo fascismo à profissão no processo de institucionalização, de 1930 a 1950. Pretende-se também identificar assistentes sociais[1] que se foram envolvendo em movimentos de oposição e resistência ao regime e perceber como, nos anos 1960 e 1970, a profissão se foi distanciando do significado inicialmente atribuído, a partir da organização sindical corporativista. Palavras-Chave: fascismo; Portugal; oposição; resistência; Serviço Social; distanciamento; ação sindical; assistentes sociais. Abstract – The concept of social work as a profession is inseparable from the development of capitalist social relations, and does not constitute a homogeneous bloc. According to Netto, the corporate projects in dispute for the maintenance or transformation of the existing social structures are expressed in professional projects. In this way, this work seeks to contribute to the analysis of the construction of social work in Portugal, grasping the meaning attributed by fascism to the profession in the process of institutionalization, from 1930 to 1950. It is also intended to identify social workers[2] who have been involved in movements of opposition and resistance to the regime and to perceive how, in the 1960s and 1970s, the profession was distanced of the initially attributed meaning, from the corporatist trade union organization. Keywords: fascism in Portugal; opposition; resistance; social work; distancing; union action; social workers. [1] Entrevistas realizadas pela autora a: Maria Eugénia Varela Gomes (26 de junho de 2000), Maria Gabriela Figueiredo Ferreira (15 e 22 de janeiro de 2001) e Maria Teresa Abrantes Pereira Ávila (20 de junho de 2000). [2] Interviews conducted by the author to: Maria Eugénia Varela Gomes (June 26, 2000), Maria Gabriela Figueiredo Ferreira (January 15 and 22, 2001) and Maria Teresa Abrantes Pereira Avila (June 20, 2000).
NOVAS REALIDADES DO ENSINO SUPERIOR A DISTÂNCIA: A INCLUSÃO DE UNIVERSITÁRIOS COM DEFICIÊNCIA
Authors: Dillenburg Andreia Ines , Cecchin Andrea Forgiarini 
Published: February 2018

Com o presente artigo pretende-se apresentar ações, desafios e legislações que tem permeado os processos de inclusão no Curso de Pedagogia a distância da Universidade Federal de Santa Maria. A instituição de ensino está localizada no interior do estado do Rio Grande do Sul, Brasil a partir implementação da Resolução 011\2007.Na atual conjuntura a EAD tem assumido novos desafios como a inclusão educacional de acadêmicos com deficiência nos cursos a distância. Atualmente o curso possui seis estudantes incluídos em um universo de 399 alunos. A equipe do curso - coordenação, professores e tutores - tem empenhado esforços para que o processo de inclusão dê conta, não só da permanência como também da qualidade dos processos de ensino desses sujeitos. Compreende-se que, uma vez garantido o acesso ao deficiente, é necessário pensar ações e debates que busquem a permanência e a efetiva aprendizagem desses alunos, assegurando a formação de um profissional apto ao mercado de trabalho. Este artigo procura tratar dos desafios encontrados pela coordenação do curso para a inclusão destes estudantes e das estratégias adotadas para dar conta desse processo. O principal expediente utilizado foi a tentativa de despertar um olhar atento aos estudantes que acessam a universidade respeitando as suas demandas e peculiaridades, evitando considerá-lo como um número, um dado estatístico.
Laparoscopic cholecystectomy: a prospective cohort study assessing the impact of grade of operating surgeon on operative time and 30-day morbidity
Authors: Tafazal H , Spreadborough P , Zakai D , Shastri-Hurst N , Ayaani S , Hanif M 
Published: February 2018

Introduction There is an increasing trend towards day case surgery for uncomplicated gallstone disease. The challenges of maximising training opportunities are well recognised by surgical trainees and the need to demonstrate timely progression of competencies is essential. Laparoscopic cholecystectomy provides the potential for excellent trainee learning opportunities. Our study builds upon previous work by assessing whether measures of outcome are still affected when cases are stratified based on procedural difficulty. Material and methods A prospective cohort study of all laparoscopic cholecystectomies conducted at a district general hospital between 2009 and 2014, performed under the care of a single consultant. The operative difficulty was determined using the Cuschieri classification. The primary endpoint was duration of operation. Secondary endpoints included length of hospital stay, delayed discharge rate and 30-day morbidity. Results A total of 266 laparoscopic cholecystectomies were performed during the study period. Mean operative time for all consultant-led cases was 52.5 minutes compared with 51.4 minutes for trainees (P = 0.67 unpaired t-test). When cases were stratified for difficulty, consultant-led cases were on average 5 minutes faster. Median duration of hospital stay was equivalent in both groups and there was no statistical difference in re-attendance (12.9% vs. 15.3% P = 0.59) or re-admission rates (3.2% vs. 8.1% P = 0.10) at 30 days. Conclusions Our study provides evidence that laparoscopic cholecystectomy provides a good training opportunity for surgical trainees without being detrimental to patient outcome. We recommend that, in selected patients, under consultant supervision, laparoscopic cholecystectomy can be performed primarily by the surgical trainee without impacting on patient outcome or theatre scheduling.
Quantification of Theophylline in Guinea Pig Plasma by LC-MS/MS Using Hydrophilic Interaction Liquid Chromatography Stationary Phase: Method Development, Validation, and Application in Study
Authors: Kertys M , Urbanova A , Mokry J 
Published: February 2018

AbstractTheophylline has been used in the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD) for over 70 years. In order to maximize the effectiveness and safety of theophylline therapy it is important to individualize the dosage of the drug. In our study we focused on determination of theophylline concentrations in guinea pig plasma. A rapid, specific, and reliable LC-MS/MS-based method was developed and validated according to European Medicine Agency (EMA) guidelines. A hydrophilic interaction liquid chromatography (HILIC) separation mode for reduction time of sample preparation was used. The analysed sample was quantified in a positive ionization mode. Multiple reaction monitoring (MRM) using transition m/z 181.06→124.06 and m/z 187.17→127.06 was performed to quantify theophylline with deuterated internal standard ([2H6]-theophylline), respectively. Modification of collision energies was performed in parallel with chromatographic separation to further eliminate interference from the matrix. The method was validated for a range of 0.5 to 30 μg/mL of plasma sample. The intra-day and inter-day precision and accuracy of the quality control samples at low, me dium, and high concentration levels exhibited relative standard deviations (RSD) of less than 10 %. The method was successfully applied for the quantitation of theophylline in guinea pig plasma for better understanding its effects in a model of ovalbumin-induced allergic inflammation.
Broadband and scalable optical coupling for silicon photonics using polymer waveguides
Authors: La Porta Antonio , Weiss Jonas , Dangel Roger , Jubin Daniel , Meier Norbert , Horst Folkert , Offrein Bert Jan 
Published: February 2018

Abstract
We present optical coupling schemes for silicon integrated photonics circuits that account for the challenges in large-scale data processing systems such as those used for emerging big data workloads. Our waveguide based approach allows to optimally exploit the on-chip optical feature size, and chip- and package real-estate. It further scales well to high numbers of channels and is compatible with state-of-the-art flip-chip die packaging. We demonstrate silicon waveguide to polymer waveguide coupling losses below 1.5 dB for both the O- and C-bands with a polarisation dependent loss of <1 dB. Over 100 optical silicon waveguide to polymer waveguide interfaces were assembled within a single alignment step, resulting in a physical I/O channel density of up to 13 waveguides per millimetre along the chip-edge, with an average coupling loss of below 3.4 dB measured at 1310 nm.
A Logical Approach to Modal Verbs 1 Can and Could
Authors: Imre Attila 
Published: February 2018

AbstractThe article aims at a logical approach to discussing can, could, and be able to, organized around core meanings such as possibility, ability, and permission. We argue that the concept of “remoteness” proposed by Lewis in 1986 may simplify enough the explanation regarding the relationship between can and could, and their presentation relies on authoritative sources published for international (English), Hungarian, and Romanian students. The conclusion discusses both the importance and relativity of a number of occurrences (depending on different text types), trying to offer a possible teaching option for modals stemming from practice. The article is connected to the international conference in Miercurea Ciuc, entitled Idegen - Străinul - Stranger, focusing on English as a foreign language through the eyes of non-native speakers.
Assessment of total fatness and fatty tissue distribution in young active and physically inactive women
Authors: Kopiczko Anna , Bogucka Aleksandra 
Published: February 2018

Summary
Study aim: The aim of the study was to evaluate the total fat and fat distribution in young active and physically inactive women. Material and methods: The study group consisted of a total of 300 students from Warsaw aged 20 to 25 years. The weekly physical activity level expressed in metabolic equivalent task was assessed using the International Physical Activity Question­naire. The distribution of adipose tissue was assessed on the basis of anthropometric measurements by somatometry. The waist and hip circumference, body mass and height were measured. Body mass index and waist to hip ratio were calculated. General fat was evaluated by bioelectric impedance. Results: Physically active students had significantly lower (p < 0.001) body mass, waist and hip circumference, lower body fat content and lower BMI and WHR compared to inactive students. Weight loss and the gynoidal type of adipose tissue distribu­tion were more frequent among physically active subjects. In inactive women the androidal-abdominal type of distribution dominated. A healthy somatic profile characterized by BMI in the normal range, gynoid type of adipose tissue distribution and normal or slightly lower body fat was significantly more frequent in physically active subjects (36% vs. 15%). Conclusions: Lack of physical activity was associated with larger waist and hip circumference, higher BMI and unfavorable adipose tissue distribution (androidal), which increases the risk of metabolic diseases in women. The study indicates the need for education and implementation of disease prevention programs regarding abdominal fat distribution and overweight among young women.