bluuebunny/crossref_metadata_2025 huggingface dataset:
The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age
Authors: Szécsényi-Nagy Anna , Roth Christina , Brandt Guido , Rihuete-Herrada Cristina , Tejedor-Rodríguez Cristina , Held Petra , García-Martínez-de-Lagrán íñigo , Magallón Héctor Arcusa , Zesch Stephanie , Knipper Corina , Bánffy Eszter , Friederich Susanne , Meller Harald , Ramírez Primitiva Bueno , Bermejo Rosa Barroso , Balbín Behrmann Rodrigo de , Herrero-Corral Ana M. , Fernández Raúl Flores , Fernández Carmen Alonso , Jiménez Echevarria Javier , Rindlisbacher Laura , Oliart Camila , Fregeiro María-Inés , Soriano Ignacio , Vicente Oriol , Micó Rafael , Lull Vicente , Díaz Jorge Soler , López Padilla Juan Antonio , Togores Muñoz Consuelo Roca de , Hernández Pérez Mauro S. , Maestre Francisco Javier Jover , Maurandi Joaquín Lomba , Fernández Azucena Avilés , Lillios Katina T. , Silva Ana Maria , Ramalho Miguel Magalhães , Oosterbeek Luiz Miguel , Cunha Claudia , Waterman Anna J. , Buxó Jordi Roig , Martínez Andrés , Martínez Juana Ponce , Ortiz Mark Hunt , Mejías-García Juan Carlos , Espín Juan Carlos Pecero , Briones Rosario Cruz-Auñón , Tomé Tiago , Ballestero Eduardo Carmona , Cardoso João Luís , Araújo Ana Cristina , Lettow-Vorbeck Corina Liesau von , Bosqued Concepción Blasco , Ríos Mendoza Patricia , Pujante Ana , Royo-Guillén José I. , Esquembre Beviá Marco Aurelio , Santos Goncalves Victor Manuel Dos , Parreira Rui , Hernández Elena Morán , Izquierdo Elena Méndez , Miguel Jorge Vega de , García Roberto Menduiña , Calvo Victoria Martínez , Jiménez Oscar López , Krause Johannes , Pichler Sandra L. , Garrido-Pena Rafael , Kunst Michael , Risch Roberto , Rojo-Guerra Manuel A. , Haak Wolfgang , Alt Kurt W.
Published: February 2017

Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focused on the maternal genetic makeup of the Neolithic (∼ 5500-3000 BCE), Chalcolithic (∼ 3000-2200 BCE) and Early Bronze Age (∼ 2200-1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character.
A high-resolution mRNA expression time course of embryonic development in zebrafish
Authors: White Richard J. , Collins John E. , Sealy Ian M. , Wali Neha , Dooley Christopher M. , Digby Zsofia , Stemple Derek L. , Murphy Daniel N. , Hourlier Thibaut , Füllgrabe Anja , Davis Matthew P. , Enright Anton J. , Busch-Nentwich Elisabeth M.
Published: February 2017

We have produced an mRNA expression time course of zebrafish development across 18 time points from 1-cell to 5 days post-fertilisation sampling individual and pools of embryos. Using poly(A) pulldown stranded RNA-seq and a 3′ end transcript counting method we characterise the temporal expression profiles of 23,642 genes. We identify temporal and functional transcript co-variance that associates 5,024 unnamed genes with distinct developmental time points. Specifically, a class of over 100 previously uncharacterised zinc finger domain containing genes, located on the long arm of chromosome 4, is expressed in a sharp peak during zygotic genome activation. The data reveal complex and widespread differential use of exons and previously unidentified 3′ ends across development, new primary microRNA transcripts and temporal divergence of gene paralogues generated in the teleost genome duplication. To make this dataset a useful baseline reference, the data are accessible to browse and download at Expression Atlas and Ensembl.
Neural decoding of visual stimuli varies with fluctuations in global network efficiency
Authors: Cocchi Luca , Zhengyi Yang , Andrew Zalesky , Johannes Stelzer , Hearne Luke , Leonardo L. Gollo , Mattingley Jason B
Published: February 2017

Functional magnetic resonance imaging (fMRI) studies have shown that neural activity fluctuates spontaneously between different states of global synchronization over a timescale of several seconds. Such fluctuations generate transient states of high and low correlation across distributed cortical areas. It has been hypothesized that such fluctuations in global efficiency might alter patterns of activity in local neuronal populations elicited by changes in incoming sensory stimuli. To test this prediction, we used a linear decoder to discriminate patterns of neural activity elicited by face and motion stimuli presented periodically while participants underwent time-resolved fMRI. As predicted, decoding was reliably higher during states of high global efficiency than during states of low efficiency, and this difference was evident across both visual and non-visual cortical regions. The results indicate that slow fluctuations in global network efficiency are associated with variations in the pattern of activity across widespread cortical regions responsible for representing distinct categories of visual stimulus. More broadly, the findings highlight the importance of understanding the impact of global fluctuations in functional connectivity on specialised, stimulus driven neural processes.
The reliability, use and evaluation of sources of information on foodstuffs
Authors: Szlachciuk Julita , Ozimek Irena
Published: February 2017

Purpose

The purpose of this paper is to investigate how young Polish consumers perceive the selected sources of information on foodstuffs. The authors have also taken into account the consumers’ comprehension, hierarchy of importance and use of labels on food products.

Design/methodology/approach

The survey sample consisted of a group of respondents aged 16-24. The participants were students of secondary schools and universities located in Poland, on the territory of Mazovian Voivodeship. The questionnaires were distributed among the respondents: the χ2 test was used to show the impact of demographic variables, while the Spearman’s rank correlation coefficient was applied to examine the relationship between the respondents’ attentiveness to the information contained on the food packaging and its legibility and comprehensibility.

Findings

The study ascertained the existence of differences in the perception of the reliability of sources of information on foodstuffs and the declared frequency of using them. In the respondents’ opinion, the most reliable information can be obtained from nutrition consultants, family members, physicians or pharmacists. Furthermore, the analysis of the frequency of use of individual sources of information by the respondents proved that most often they relied on the recommendations from their family members, the information contained in the label and advice offered by their acquaintances.

Originality/value

The research findings indicate that the key action should be to carry out further educational activities aimed at young consumers in order to enable them to execute their rights to fair information and education, in the foodstuffs market, as well as to increase their consumer activity.
Decomposition analysis and consumer research as essential elements of the new food product development process
Authors: Halagarda Michał
Published: February 2017

Purpose

Due to fast changes in consumer demands and expectations, developing and introducing new products have become a necessity for the food companies in order to survive on the competitive market. The purpose of this paper is to investigate the usefulness of decomposition analysis in combination with consumer research in the new food product development process.

Design/methodology/approach

A survey concerning nutritional habits of consumers based on 339 respondents and an analysis of the sensory and nutritional properties of products available on the market have been performed.

Findings

It has been indicated that owing to the proposed research methods, a niche in the market can be found. It was found that products currently available on the market do not fully fulfil the essential nutritional and/or sensory criteria.

Practical implications

The set of methods used in the study provides a valuable input into the new food product development process. The results of the research show that a company that will deliver a low-caloric bakery savoury snack of high nutritional quality and successfully present its properties to customers may gain a competitive advantage.

Originality/value

The topic is relatively new. Other studies focus on complex methods, whereas this research investigates the usefulness of a set of simple but effective tools that can be used in the new food product development process.
Evaluating the usability of COMSATS Institute of Information Technology library website: a case study
Authors: Sheikh Arslan
Published: February 2017

Purpose

Library websites serve as gateways to the information resources and services of their libraries. In today’s digital age, the development of websites is inevitable for libraries as a means to provide users with online services at their desktops. This case study reports the findings of a usability study of an academic library website from the user’s perspective.

Design/methodology/approach

An online survey on the efficacy of the website and statistical reports from Google Analytics were used as tools to assess and track the use of the Commission on Science and Technology for Sustainable Development in the South (COMSATS) Institute of Information Technology’s (CIIT’s) library website resources by national and international users. A sample of 550 users was invited by e-mail to respond to the questionnaire covering various usability features of the website.

Findings

Findings reveal that users are largely satisfied with the usefulness, convenience, design and quality of CIIT library website. Moreover, the users are mostly making use of the website for accessing research papers through the Higher Education Commission (HEC) digital library, exploring free online open access journals, searching for e-books and examining the library collection via online public access catalog (OPAC). This shows that the library website has a significant role in the pedagogical activities of the CIIT community.

Research limitations/implications

The results are limited to a case study of CIIT, Islamabad campus library website.

Practical implications

The findings of this study will help the library administration to overcome existing deficiencies in the CIIT library website.

Originality/value

The study is a foremost usability evaluation of CIIT, Islamabad campus library website from the user perspective.
Scholarly communication in the age of Google
Authors: Arshad Alia , Ameen Kanwal
Published: February 2017

Purpose

The purpose of this study is to investigate the use patterns of scholarly e-journals by academics for teaching, research and keeping themselves up-to-date. The study also looks at differences in the use patterns across 12 disciplines.

Design/methodology/approach

A survey was conducted to explore academics’ use patterns of scholarly e-journals in 12 disciplines. The University of the Punjab was used for the sample population. Self-administered questionnaires were distributed to all regular and contractual academics of Lahore campuses of the University. After follow up, 457 questionnaires were received with a response rate of 54 per cent. Descriptive statistics and non-parametric statistics were used to analyse data.

Findings

The results showed that the academics made more frequent use of e-journals, online reference sources and discussion with colleagues for scholarly activities. E-journals were used predominantly for research-related activities rather than for teaching and instruction. Academics obtained e-journal articles primarily from open access sources, i.e. general search engines and Google Scholar as compared to subscribed and other sources of e-journal articles. Disciplinary differences were also found in academics’ use patterns of e-journals. However, academics showed just satisfactory skills regarding use of advanced searching techniques and evaluation of the quality of e-journals.

Practical implications

Findings will be helpful for information professionals to review their policies and practices in relation to e-journal services for academic community. The needs for e-literacy skills to use e-journals will also be identified and findings will be significant for information professionals in arranging information literacy instruction programmes for targeted disciplines.

Originality/value

Most of e-journals use studies focused on specific disciplines – Sciences, Life Sciences, Engineering and Technology and Social Sciences. This research study is valuable that investigated use patterns of e-journals across 12 different disciplines at the University of the Punjab.
Technical requirements for copyright protection of electronic theses and dissertations in INSTD
Authors: Papi Zeinab , Rezaei Sharifabadi Saeid , Mohammadesmaeil Sedigheh , Hariri Nadjla
Published: February 2017

Purpose

This study aims to determine the technical requirements for copyright protection of theses and dissertations for proposing a model for applying in Iran’s National System for Theses and Dissertations (INSTD).

Design/methodology/approach

This study used a mixed research methodology. The grounded theory was used in the qualitative phase, and a researcher-made checklist was applied in the quantitative phase for surveying the status of the INSTD. Research population included INSTD as well as six information specialists and copyright experts. Data were analysed by using open, axial and selective coding.

Findings

Based on data extracted from the completed checklists, some technical requirements had been provided in the system. The technical requirements that interviewees pointed out included the following two main classes: technical components and technical-software infrastructures, explored in the phase of the grounded theory. The individual categories included access control, copy control, technical-software challenges, protecting standards, hypertext transfer protocol secure, certificate authority, documentation of thesis and dissertation information, the use of digital object identifiers, copy detection systems, thesis and dissertation integrated systems, digital rights management systems and electronic copyright management systems.

Research limitations/implications

Considering the subject of this study, only the technical aspect was investigated, and other aspects were not included. In addition, electronic theses and dissertation (ETD) providers were not well aware of copyright issues.

Practical implications

Using the technical requirements with high security is effective in the INSTD to gain the trust of the authors and encourage them to deposit their ETDs.

Social implications

The increased use of the system encourages the authors to be more innovative in conducting their research.

Originality/value

Considering the continued violation of copyright in electronic databases, applying technical requirements for copyright protection and regulating users’ access to the information of theses and dissertations are needed in the INSTD.
The effect of parent university on firm growth: an analysis of the Spanish and Italian USOs
Authors: Corsi Christian , Prencipe Antonio , Rodríguez-Gulías María Jesús , Fernández-López Sara , Rodeiro-Pazos David
Published: February 2017

Purpose

The purpose of this paper is to explore the hypothesis that the university context may partially determine the growth of university spin-offs (USOs), with a cross-national analysis and using an “interactionist” approach.

Design/methodology/approach

Two samples of USOs, from Spain and Italy (531 and 952 firms, respectively), were examined over the 2005-2013 period. Multilevel modelling was applied to empirically test the hypotheses.

Findings

The results confirmed that the university context is a critical and effective element for explaining USOs’ growth. The university context affected USOs’ growth only for the Spanish firms, while for the Italian spin-offs the evidence does not report a significant determining influence of the university context. This finding may be interpreted as the localization externalities, determined by the Spanish universities, have a more effective impact at firm level compared with those generated by the Italian universities.

Research limitations/implications

The paper provides evidence that the university context has a significant role in supporting USOs’ growth in Spain, but not in Italy. This finding, together with the fact that the Italian USOs showed lower growth rates over the period of analysis, may suggest that greater involvement by the Italian parent universities is needed to foster USOs’ growth. The main point to be underlined to decision makers is that policies aimed at fostering USOs need the active involvement of the parent university in the whole growth process of the nascent firm, rather than just in the USO creation process.

Originality/value

A multilevel approach provides both methodological and theoretical contributions to the study of USOs’ growth, which was adopted as an “interactionist” approach is recommended by literature. In addition, a cross-national approach allows for exploration of the actual effect of the university on the growth of USOs, taking into account international differences.
Entrepreneurial university: a case study at Stony Brook University
Authors: Wolf Gerrit
Published: February 2017

Purpose

A business school within a research university can improve the startup process and success on and near campus. The purpose of this paper is to show the mutual benefits to business and science students in learning about startups and to helping startups grow. The mutual benefit comes from the student understanding and the startup managing the complementary roles of inventor, entrepreneur, and investor.

Design/methodology/approach

A case analysis using participant observation, interviews, and document review of the Innovation Center in the College of Business at the Stony Brook University tracks the development of the Center’s educational, research, and consulting activity with engineering departments, incubators, and other support services on campus.

Findings

Inventor, investor, and entrepreneurship roles were supported and coordinated by science and business faculties and students in the university. This process, described in specific courses and programs for MBAs and BBAs, includes the contribution of business academic faculty, serial entrepreneur mentors and the scientists in partner organizations that also support startups inside and outside the university. The number of business plans written by students grew from 10 to 100 a year, startups begun from 1 to 5 a year, and established startups renewed grew from 10 a year to 20 a year over five year period.

Practical implications

This case can be useful to research universities and business schools that want to improve the startup process and success.

Originality/value

This study shows that the role of students in the business school in a research university is to transform inventive ideas from the sciences to innovations in the market place through entrepreneurial activity.
Combined in vivo reflectance confocal microscopy and digital dermoscopy for follow up of patients at high risk of malignant melanoma: A prospective case series study
Authors: Floristán Muruzábal Uxúa , Gamo Villegas Reyes , Pampín Franco Ana , Pinedo Moraleda Fernando , Pérez Fernández Elia , López‐Estebaranz José Luis
Published: February 2017

Digital dermoscopy (DD) follow up is a useful strategy for monitoring patients at high risk of melanoma. Reflectance confocal microscopy (RCM) is a valuable second‐level examination after dermoscopy for the evaluation of difficult to diagnose lesions. The aim of this study was to assess the value of RCM in routine DD monitoring of patients at high risk of melanoma. In this prospective study, performed over 22 months, changing melanocytic lesions were detected by DD and excised. RCM imaging was performed before surgical excision of all the lesions, and histopathology used as the gold standard diagnostic test. Eighty‐seven lesions, including 11 thin melanomas, were studied. Dermoscopic evaluation at follow up revealed a significant association between melanoma and asymmetry in two axes (P = 0.035). Enlargement and other changes in structure or color did not significantly differ between nevi and melanomas. Widespread pagetoid cells, non‐edged papillae, irregular and dishomogeneous junctional clusters, and sheet‐like structures were significantly associated with malignancy (P < 0.001). RCM allowed accurate diagnosis of melanoma in 10 of 11 cases (90.9%). The remaining case was classified as a dysplastic nevus. Forty‐six lesions (52.8%) in which RCM revealed no atypia were deemed unnecessarily removed. This study was limited by sample size. In conclusion, combined DD and RCM facilitates the recognition of thin malignant melanomas and reduces unnecessary excisions.
High‐performance work systems and employee engagement: empirical evidence from China
Authors: Huang Yufang , Ma Zhenzhong , Meng Yong
Published: February 2017

Employee engagement and commitment has been a very important issue in human resource managers’ agenda. The present study adds to the literature by examining the impact of high‐performance work systems (HPWS) on employee attitudes and on employee engagement in China in response to the increasing interest in the universalistic effects of HPWS in the globalized world market. With the data from 782 employees working in China's manufacturing and service sectors, this study shows that HPWS are positively related to employees’ positive mood and job satisfaction, and that job satisfaction and positive mood lead to high employee engagement. Moreover, employee's positive mood and job satisfaction also mediate the relationship between HPWS and employee engagement. The result helps explore one mechanism via which HPWS affect employee behaviors and provides empirical evidence for the applicability of HPWS in an international context.
Western Australia's Domestic Gas Reservation Policy: The Elemental Economics
Authors: Neill Kelly
Published: February 2017

Western Australia's domestic gas reservation policy nominally requires new gas export projects to supply the equivalent of 15 per cent of their exports to the domestic gas market. This export restriction suppresses the domestic price below the export netback price. A theoretical model shows that a binding reservation policy always causes a deadweight loss, and clarifies the source of this loss. Western Australia's reservation policy is estimated to cause losses with a present value of between $6.9 and $22.9 billion, depending on export netback prices.
Sequence of cardiovascular autonomic alterations after fingolimod initiation
Authors: Simula Sakari , Laitinen Tomi P. , Laitinen Tiina M. , Hartikainen Päivi , Hartikainen Juha E.K.
Published: February 2017

Background

Homeostasis between heart rate and blood pressure is based on several interacting regulatory reflexes, which become influenced by fingolimod initiation. The aim of this study was to determine the sequence of changes in cardiovascular autonomic regulation after fingolimod initiation.

Methods

Twenty‐seven patients with relapsing–remitting multiple sclerosis underwent continuous electrocardiogram recording during the first 6 hr after the first dose of fingolimod. In addition to the time interval between two consecutive R‐peaks (RR interval), blood pressure and heart rate variability (HRV) were measured on hourly basis. Cardiac parasympathetic and sympathetic regulation were assessed by the different components of HRV.

Results

HRV demonstrated an enhancement in cardiac parasympathetic regulation starting 1 hr after the first dose of fingolimod. Blood pressure started to decrease 2 hr and sympathetic cardiac regulation 3 hr after fingolimod initiation. Recovery in RR interval, systolic and diastolic blood pressure, as well as in cardiac autonomic regulation started after 5 hr postdose, whereas pulse pressure (difference between systolic and diastolic blood pressure) continued to increase at the time of hospital discharge.

Conclusions

RR interval, blood pressure, as well as the parasympathetic and sympathetic components of cardiac autonomic regulation alter sequentially in different temporal pattern after fingolimod initiation. These findings enhance the understanding of the effects of fingolimod initiation on cardiovascular autonomic regulation in real life.
Systematic review of a patient care bundle in reducing staphylococcal infections in cardiac and orthopaedic surgery
Authors: Ma Ning , Cameron Alun , Tivey David , Grae Nikki , Roberts Sally , Morris Arthur
Published: February 2017

Surgical site infections (SSIs) are serious adverse events hindering surgical patients’ recovery. In Australia and New Zealand, SSIs are a huge burden to patients and healthcare systems. A bundled approach, including pre‐theatre nasal and/or skin decolonization has been used to reduce the risk of staphylococcal infection. The aim of this review is to assess the effectiveness of the bundle in preventing SSIs for cardiac and orthopaedic surgeries. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Published literature was searched in PubMed, Embase and Cochrane Library of Systematic reviews. Identified articles were selected and extracted based on a priori defined Population‐Intervention‐Comparator‐Outcome and eligibility criteria. Data of randomized controlled trials (RCTs) and comparative observational studies were synthesized by meta‐analyses. Quality appraisal tools were used to assess the evidence quality. The review included six RCTs and 19 observational studies. The bundled treatment regimens varied substantially across all studies. RCTs showed a trend of Staphylococcus aureus SSIs reduction due to the bundle (relative risk = 0.59, 95% confidence interval (CI) = 0.33, 1.06) with moderate heterogeneity. Observational studies showed statistically significant reduction in all‐cause and S. aureus SSIs, with 51% (95% CI = 0.41, 0.59) and 47% (95% CI = 0.35, 0.65), respectively. No publication biases were detected. SSIs in major cardiac and orthopaedic surgeries can be effectively reduced by approximately 50% with a pre‐theatre patient care bundle approach.
Material, Political, and Biopolitical Dimensions of “Waste” in California Water Law
Authors: Cantor Alida
Published: February 2017

California's state constitution prohibits the “wasteful” use of water; however, waste is subjective and context dependent. This paper considers political, biopolitical, and material dimensions of waste, focusing on the role of legal processes and institutions. The paper examines a case involving legal accusations of “waste and unreasonable use” of water by the Imperial Irrigation District in Imperial County, California. The determination that water was being “wasted” justified the transfer of water from agricultural to urban areas. However, defining these flows of water as a waste neglected water's complexity and relationality, and the enclosure of a “paracommons” threatens to bring about negative environmental and public health consequences. The paper shows that the project of discursively labeling certain material resource flows as waste and re‐allocating these resources to correct this moral and economic failure relies upon legal processes, and carries political and biopolitical implications.
A Generalized Fellner-Schall Method for Smoothing Parameter Optimization with Application to Tweedie Location, Scale and Shape Models
Authors: Wood Simon N. , Fasiolo Matteo
Published: February 2017

We consider the optimization of smoothing parameters and variance components in models with a regular log likelihood subject to quadratic penalization of the model coefficients, via a generalization of the method of Fellner (1986) and Schall (1991). In particular: (i) we generalize the original method to the case of penalties that are linear in several smoothing parameters, thereby covering the important cases of tensor product and adaptive smoothers; (ii) we show why the method's steps increase the restricted marginal likelihood of the model, that it tends to converge faster than the EM algorithm, or obvious accelerations of this, and investigate its relation to Newton optimization; (iii) we generalize the method to any Fisher regular likelihood. The method represents a considerable simplification over existing methods of estimating smoothing parameters in the context of regular likelihoods, without sacrificing generality: for example, it is only necessary to compute with the same first and second derivatives of the log-likelihood required for coefficient estimation, and not with the third or fourth order derivatives required by alternative approaches. Examples are provided which would have been impossible or impractical with pre-existing Fellner-Schall methods, along with an example of a Tweedie location, scale and shape model which would be a challenge for alternative methods, and a sparse additive modeling example where the method facilitates computational efficiency gains of several orders of magnitude. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Programmed death‐ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor
Authors: Zhang Wencheng , Pang Qingsong , Zhang Xiaodong , Yan Cihui , Wang Qifeng , Yang Jinsong , Yu Shufei , Liu Xiao , Pan Yi , Yuan Zhiyong , Wang Ping , Xiao Zefen
Published: February 2017

Programmed death‐ligand 1 (PD‐L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD‐L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD‐L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD‐L1 was present both on the surface of tumor cells and tumor‐infiltrating immune cells. Patients with tumor‐infiltrating immune cell PD‐L1 expression had better survival. PD‐L1 expression on immune cells was an independent prognostic factor for patients with ESCC. PD‐L1 expression either on tumor‐infiltrating immune cells or tumor cells was negatively associated with EGFR expression. EGFR/PD‐L1 pairs could separate the survival between EGFR low/PD‐L1 positive and EGFR high/PD‐L1 negative groups. In ESCC cell lines with EGFR high expression, PD‐L1 expression was induced significantly when EGFR signaling was activated by radiation and was dramatically inhibited by an EGFR tyrosine kinase inhibitor. In conclusion, tumor‐infiltrating immune cell PD‐L1 expression is an independent prognostic factor for ESCC, and the association between EGFR and PD‐L1 is vital to determining survival. It is important to consider radiotherapy‐induced imbalance of pro‐tumor and anti‐tumor immune response. A combination of radiotherapy and PD‐L1‐targeted therapy could be a promising therapeutic strategy for ESCC patients.
SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib
Authors: Ohoka Nobumichi , Nagai Katsunori , Shibata Norihito , Hattori Takayuki , Nara Hiroshi , Cho Nobuo , Naito Mikihiko
Published: February 2017

We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP‐dependent Protein ERaser) against transforming acidic coiled‐coil‐3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) and paraptosis‐like cell death selectively in cancer cells. Mechanistic analysis suggests that accumulation of ubiquitylated protein aggregates that requires X‐linked inhibitor of apoptosis protein (XIAP) induces ER stress, which results in ER‐stress responses involving X‐box binding protein‐1 (XBP‐1) and ER‐derived vacuolization in cancer cells. Importantly, inhibition of proteasome enhanced the SNIPER(TACC3)‐induced vacuolization, and the combination treatment of SNIPER(TACC3) and bortezomib exhibited a synergistic anticancer activity in several cancer cell lines. The induction of paraptosis‐like cell death in cancer cells by SNIPER(TACC3) could be applied to treat cancer cells resistant to undergo apoptosis by overexpression of XIAP.
Control of lymphocyte trafficking and adaptive immunity by adrenergic nerves
Authors: Suzuki Kazuhiro , Nakai Akiko
Published: February 2017

The nervous and immune systems are the principal organ systems that sense internal and external environments, and evoke adaptive responses to maintain homeostasis. Studies in the past few decades discovered commonalities between the two organ systems. They share many functional molecules and respond to various stimuli with high specificity. Additionally, it has long been suggested that there is also cross‐talk between the nervous and immune systems. However, the cellular and molecular basis for neuroimmune interactions has emerged only in the past decade. Adrenergic nerves constitute the efferent arc of the sympathetic nervous system and coordinate organ functions in the entire body. Recently, studies have shown that adrenergic nerves regulate the trafficking of myeloid and lymphoid immune cells through distinct molecular mechanisms. In the present review, we focus on the role of adrenergic nerves in the control of lymphocyte trafficking and adaptive immune responses in physiological and pathological conditions.
Oculomotor deficits in spinocerebellar ataxia type 3: Potential biomarkers of preclinical detection and disease progression
Authors: Wu Chao , Chen Ding‐Bang , Feng Li , Zhou Xiang‐Xue , Zhang Ji‐Wei , You Hua‐Jing , Liang Xiu‐Ling , Pei Zhong , Li Xun‐Hua
Published: February 2017

Aims

To detect specific oculomotor deficits in preclinical stage of spinocerebellar ataxia type 3 (SCA3) and evaluate whether these abnormalities prove useful as potential biomarkers of disease progression.

Methods

A Chinese cohort of 56 patients withSCA3, including 12 preclinical carriers ofSCA3 (pre‐SCA3) and 44 manifestSCA3, and 26 healthy control individuals were recruited. We performed a detailed investigation on central oculomotor performance including fixation, gaze, smooth pursuit, prosaccade, and antisaccade using video‐oculography.

Results

Common oculomotor features of pre‐SCA3 included square‐wave jerk during central fixation and gaze holding, impaired vertical smooth pursuit, slow upward saccade, and increased antisaccade error rate. In ourSCA3 cohort, all oculomotor parameters were correlated with the score of the Scale for the Assessment and Rating of Ataxia, whilst some of them were correlated with disease duration.

Conclusion

This study showed that a series of neuropathological changes reflected by oculomotor abnormalities appeared preferentially in preclinical stage ofSCA3. Accordingly, objective oculomotor preclinical signs may be useful to detect the optimum time‐point for therapeutic interventions in future clinical trials ofSCA3. Larger and longitudinal data are warranted to confirm our results.
Treatment with the glucagon receptor antagonist LY2409021 increases ambulatory blood pressure in patients with type 2 diabetes
Authors: Kazda Christof M. , Frias Juan , Foga Irene , Cui Xuewei , Guzman Cristina B. , Garhyan Parag , Heilmann Cory , Yang Jihui Anne , Hardy Thomas A.
Published: February 2017

Aims

To assess the effect of LY2409021 on systolic blood pressure (SBP) in patients with type 2 diabetes.

Materials and methods

This 6‐week, randomized, crossover study evaluated the effects of once‐daily administration of LY2409021 20 mg vs those of placebo on SBP, diastolic BP (DBP), and mean arterial pressure (MAP) using 24‐hour ambulatory BP monitoring (ABPM) in 270 subjects treated with diet/exercise ± metformin. Other measures included changes in glycemic control, serum lipids, and hepatic safety markers.

Results

At 6 weeks of LY2409021 treatment, 24‐hour mean SBP was increased, with a least squares mean (LSM) difference of 2.26 mm Hg vs placebo (95% CI: 1.11, 3.40;
P
 < .001). The 24‐hour mean DBP and MAP also increased, with LSM differences of 1.37 mm Hg (95% CI: 0.66, 2.08;
P
 < .001) and 1.67 mm Hg (95% CI: 0.86, 2.47;
P
 < .001) vs placebo, respectively. At week 6, LY2409021 treatment reduced glycated hemoglobin (HbA1c) levels, with an LSM difference of −0.49% (−5.4 mmol/mol) (95% CI: −0.56%, −0.42% [−6.1, −4.6 mmol/mol];
P
 < .001) vs placebo. Mean HbA1c at baseline was 7.3% (56 mmol/mol). Small but significant changes in serum lipid and aminotransferase levels were observed with LY2409021 treatment (all
P
 < .05 vs placebo).

Conclusions

Statistically significant increases in BP, MAP and serum lipid levels were observed with LY2409021 treatment at a dose that lowered HbA1c and glucose levels. These effects may limit the clinical utility of LY2409021 as a chronic treatment for type 2 diabetes.
Aortic root thrombus complicated by left main coronary artery occlusion visualized by 3D echocardiography in a patient with continuous‐flow left ventricular assist device
Authors: Tanna Monique S. , Reyentovich Alex , Balsam Leora B. , Dodson John A. , Vainrib Alan F. , Benenstein Ricardo J. , Rosenzweig Barry P. , Saric Muhamed
Published: February 2017

Aortic root thrombus is an uncommon complication of continuous‐flow left ventricular assist devices (LVAD). We present the case of a 71‐year‐old man with ischemic cardiomyopathy who underwent destination therapy HeartMate II LVAD placement. Eighteen months later, he presented with a cerebrovascular accident followed by myocardial infarction. Transesophageal echocardiography revealed an aortic root thrombus spanning the left and noncoronary cusps and obliterating the left main coronary artery. We discuss the incidence, risk factors, and management of aortic root thrombus in LVAD patients. To our knowledge, this is the first report of three‐dimensional echocardiography used to characterize an LVAD‐associated aortic root thrombus.
Right ventricular systolic function in hypoplastic left heart syndrome: A comparison of manual and automated software to measure fractional area change
Authors: Ruotsalainen Hanna K. , Bellsham‐Revell Hannah R. , Bell Aaron J. , Pihkala Jaana I. , Ojala Tiina H. , Simpson John M.
Published: February 2017

Background

Quantitative echocardiographic assessment of right ventricular function is important in children with hypoplastic left heart syndrome (HLHS). The aim of this study was to examine the repeatability of different echocardiographic techniques, both manual and automated, to measure fractional area change (FAC) in patients with HLHS and to correlate these measurements with magnetic resonance imaging (MRI)‐derived ejection fraction (EF).

Methods

Fifty‐one children with HLHS underwent transthoracic echocardiography and cardiac MRI under the same general anesthetic as part of routine inter‐stage assessment. FAC was measured from the apical four‐chamber view using three different techniques: velocity vector imaging (VVI) (Syngo USWP 3.0; Siemens Healthineers), QLAB (Q‐lab R 10.0; Philips Healthcare), and manual endocardial contour tracing (Xcelera, Philips Healthcare). Intra‐ and inter‐observer variability was calculated using intra‐class correlation coefficient (ICC). FAC was correlated with MRI EF calculated using a single standard method.

Results

Fractional area change had a good correlation with MRI‐derived EF with an R value for VVI, QLAB, and manual methods of .7, .6, and .4, respectively. Intra‐ and inter‐observer variability for FAC was good for automated echocardiographic methods (ICC>.85) but worse for manual method particularly inter‐observer variability of FAC and end‐systolic area. Both automated techniques tended to produce higher FAC values compared with manual measurements (P<.001).

Conclusion

Automation improves the repeatability of FAC in HLHS. There are some differences between automated software in terms of correlation with MRI‐derived EF. Measurement bias and wide limits of agreement mean that the same echocardiographic technique should be used during the follow‐up of individual patients.
EFFECTS OF WELFARE REFORM ON WOMEN'S VOTING PARTICIPATION
Authors: Corman Hope , Dave Dhaval , Reichman Nancy E.
Published: February 2017

This study investigates the effects of welfare reform in the United States in the 1990s on voting among low‐income women. Using the November Current Population Surveys with the added Voting and Registration Supplement for the years 1990 through 2004 and exploiting changes in welfare policy across states and over time, we estimate the causal effects of welfare reform on women's voting registration and voting participation during the period in which welfare reform unfolded. During this time period, voter turnout was decreasing in the United States. We find robust evidence that welfare reform led to smaller declines in voting (about 3 to 4 percentage points, which translates to about 10% relative to the baseline mean) for women who were exposed to welfare reform compared to several different comparison groups of similar women who were much less exposed. The robust findings suggest that welfare reform had prosocial effects on civic participation, as characterized by voting. The effects were largely confined to presidential elections, were stronger in Democratic than Republican states, were stronger in states with stronger work incentive policies, and appeared to operate through employment, education, and income. (JEL D72, H53, I38, J21)
The susceptibility of selected conifer foliage to infection with Phytophthora lateralis
Authors: Schlenzig A. , Campbell R. B. , Roberts A. M. I.
Published: February 2017

The foliage of seven different genera of conifers including 10 species and 17 different cultivars was tested for its susceptibility against two isolates of Phytophthora lateralis from two different lineages. Detached green shoot tips were floated in zoospore suspension and the lesion size was assessed after 7 days. xCupressocyparis leylandii, Juniperus media and Cedrus deodara were the most resistant hosts, whereas Chamaecyparis obtusa was most susceptible. Thuja plicata and Thuja occidentalis, Chamaecyparis pisifera and Chamaecyparis lawsoniana, Taxus baccata and Cupressus macrocarpa were of medium susceptibility. For comparison, a small subset of four hosts was also tested for stem susceptibility. The stems of whole potted plants were inoculated with the same two isolates as used for the leaf susceptibility tests. Chamaecyparis lawsoniana was highly susceptible, whereas the stems of xC. leylandii, T. baccata and T. plicata were not susceptible. Most conifers were similarly affected by both tested lineages of P. lateralis although the isolate of the Pacific Northwest lineage caused slightly longer lesions on C. lawsoniana in the stem inoculation tests.
Involvement of the phosphoinositide 3‐kinase/Akt signaling pathway in bone morphogenetic protein 9‐stimulated osteogenic differentiation and stromal cell‐derived factor 1 production in human periodontal ligament fibroblasts
Authors: Furue Kirara , Sena Kotaro , Sakoda Kenji , Nakamura Toshiaki , Noguchi Kazuyuki
Published: February 2017

Recent studies have shown that bone morphogenetic protein 9 (BMP‐9) can induce osteogenic differentiation in human periodontal stem cells and human periodontal ligament fibroblasts (PDLFs). Bone morphogenetic protein 9 may be used in periodontal tissue regeneration because of its potent osteoinductive ability. Human periodontal ligament cells also have been demonstrated to produce stromal cell‐derived factor 1 (SDF‐1), which is important for stem‐cell homing and recruitment to injured sites. In the present study, we examined the involvement of the phosphoinositide 3‐kinase (PI3K)/Akt signaling axis in osteogenic differentiation and SDF‐1 production in human PDLFs stimulated with BMP‐9 in osteogenic medium supplemented with dexamethasone and ascorbic acid. Pretreatment of the cells with LY294002, a PI3K‐specific inhibitor, suppressed not only BMP‐9‐enhanced alkaline phosphatase activity but also expression of a BMP‐response gene (inhibitor of DNA binding 1) and osteogenic marker genes (runt‐related transcription factor 2, osterix, bone sialoprotein, and osteopontin). In addition, BMP‐9 up‐regulated SDF‐1 production, and the production of SDF‐1 was suppressed by LY294002. The protein SDF‐1‐alpha was identified as a major isoform of SDF‐1 that was regulated by BMP‐9. Our data suggest involvement of the PI3K/Akt pathway in BMP‐9‐stimulated osteogenic differentiation and SDF‐1 production in PDLFs cultured in osteogenic medium.
Ca2+‐permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma
Authors: Kitaura Hiroki , Sonoda Masaki , Teramoto Sayaka , Shirozu Hiroshi , Shimizu Hiroshi , Kimura Tadashi , Masuda Hiroshi , Ito Yosuke , Takahashi Hitoshi , Kwak Shin , Kameyama Shigeki , Kakita Akiyoshi
Published: February 2017

Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+ permeability through α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+‐permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+‐permeable AMPA receptors due to dislocation of ADAR2.