bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting cancer outcomes from histology and genomics using convolutional networks
Authors: Mobadersany Pooya , Yousefi Safoora , Amgad Mohamed , Gutman David A. , Barnholtz-Sloan Jill S. , Velázquez Vega José E. , Brat Daniel J. , Cooper Lee A. D. 
Published: March 2018

Significance
Predicting the expected outcome of patients diagnosed with cancer is a critical step in treatment. Advances in genomic and imaging technologies provide physicians with vast amounts of data, yet prognostication remains largely subjective, leading to suboptimal clinical management. We developed a computational approach based on deep learning to predict the overall survival of patients diagnosed with brain tumors from microscopic images of tissue biopsies and genomic biomarkers. This method uses adaptive feedback to simultaneously learn the visual patterns and molecular biomarkers associated with patient outcomes. Our approach surpasses the prognostic accuracy of human experts using the current clinical standard for classifying brain tumors and presents an innovative approach for objective, accurate, and integrated prediction of patient outcomes.
Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration
Authors: Vighi Eleonora , Trifunović Dragana , Veiga-Crespo Patricia , Rentsch Andreas , Hoffmann Dorit , Sahaboglu Ayse , Strasser Torsten , Kulkarni Manoj , Bertolotti Evelina , van den Heuvel Angelique , Peters Tobias , Reijerkerk Arie , Euler Thomas , Ueffing Marius , Schwede Frank , Genieser Hans-Gottfried , Gaillard Pieter , Marigo Valeria , Ekström Per , Paquet-Durand François 
Published: March 2018

Significance
Development of treatments for hereditary degeneration of the retina (RD) is hampered by the vast genetic heterogeneity of this group of diseases and by the delivery of the drug to an organ protected by the blood–retina barrier. Here, we present an approach for the treatment of different types of RD, combining an innovative drug therapy with a liposomal system that facilitates drug delivery into the retina. Using different animal models of RD we show that this pharmacological treatment preserved both the viability of cells in the retina as well as retinal function. Thus, our study provides an avenue for the development of therapies for hereditary diseases which cause blindness, an unmet medical need.
Fatty-acid–binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses
Authors: Haj-Dahmane Samir , Shen Roh-Yu , Elmes Matthew W. , Studholme Keith , Kanjiya Martha P. , Bogdan Diane , Thanos Panayotis K. , Miyauchi Jeremy T. , Tsirka Stella E. , Deutsch Dale G. , Kaczocha Martin 
Published: March 2018

Significance
Endocannabinoids (eCBs), a family of active lipids, modulate synaptic transmission in the brain. Research conducted over the past decades has delineated the mechanisms by which eCBs control synaptic function. However, how these lipids are transported through the aqueous milieu of the synaptic cleft to engage cannabinoid receptors and ion channels remains a long-standing question in the field of eCB research. Here, we identify fatty-acid–binding protein 5 as a modulator of retrograde eCB signaling in the brain, which mediates the synaptic transport of the eCB 2-arachidonoyl glycerol. This protein may also control the synaptic transport of other eCBs and lipid-signaling molecules in the brain.
Distinguishing the roles of dorsolateral and anterior PFC in visual metacognition
Authors: Shekhar Medha , Rahnev Dobromir 
Published: March 2018

AbstractVisual metacognition depends on regions within the prefrontal cortex. Two areas in particular have been repeatedly implicated: the dorsolateral prefrontal cortex (DLPFC) and the anterior prefrontal cortex (aPFC). However, it is still unclear what the function of each of these areas is and how they differ from each other. To establish the specific roles of DLPFC and aPFC in metacognition, we employed online transcranial magnetic stimulation (TMS) to causally interfere with their functioning during confidence generation. Human subjects from both sexes performed a perceptual decision-making task and provided confidence ratings. We found a clear dissociation between the two areas: DLPFC TMS lowered confidence ratings, whereas aPFC TMS increased metacognitive ability but only for the second half of the experimental blocks. These results support a functional architecture where DLPFC reads out the strength of the sensory evidence and relays it to aPFC, which makes the confidence judgement by potentially incorporating additional, non-perceptual information. Indeed, simulations from a model that incorporates these putative DLPFC and aPFC functions reproduced our behavioral results. These findings establish DLPFC and aPFC as distinct nodes in a metacognitive network and suggest specific contributions from each of these regions to confidence generation.SignificanceThe prefrontal cortex (PFC) is known to be critical for metacognition. Two of its sub-regions - dorsolateral PFC (DLPFC) and anterior PFC (aPFC) - have specifically been implicated in confidence generation. However, it is unclear if these regions have distinct functions related to the underlying metacognitive computation. Using a causal intervention with transcranial magnetic stimulation (TMS), we demonstrate that DLPFC and aPFC have dissociable contributions: targeting DLPFC decreased average confidence ratings, while targeting aPFC specifically affected metacognitive scores. Based on these results, we postulated specific functions for DLPFC and aPFC in metacognitive computation and corroborated them using a computational model that reproduced our results. Our causal results reveal the existence of a specialized modular organization in PFC for confidence generation.
Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro
Authors: Bikson Marom , Ruiz-Nuño Ana , Miranda Dolores , Kronberg Greg , Jiruska Premysl , Fox John E , Jefferys John G.R. 
Published: March 2018

AbstractIt is well established that non-synaptic mechanisms can generate electrographic seizures after blockade of synaptic function. We investigated the interaction of intact synaptic activity with non-synaptic mechanisms in the isolated CA1 region of rat hippocampal slices using the “elevated-K+” model of epilepsy. Elevated K+ ictal bursts share waveform features with other models of electrographic seizures, including non-synaptic models where chemical synaptic transmission is suppressed, such as the low-Ca2+model. These features include a prolonged (several seconds) negative field shift associated with neuronal depolarization and superimposed population spikes. When population spikes are disrupted for up to several seconds, intracellular recording demonstrated that the prolonged suppression of population spikes during ictal activity was due to depolarization block of neurons. Elevated-K+ ictal bursts were often preceded by a build-up of “pre-ictal” epileptiform discharges that were characterized as either “slow-transition” (localized and with a gradual increase in population spike amplitude, reminiscent non-synaptic neuronal aggregate formation, presumed mediated by extracellular K+ concentrations ([K+])o accumulation), or “fast-transition” (with a sudden increase in population spike amplitude, presumed mediated by field effects). When ictal activity had a fast-transition it was preceded by fast-transition pre-ictal activity; otherwise population spikes developed gradually at ictal event onset. Addition of bicuculline, a GABAA receptor antagonist, suppressed population spike generation during ictal activity, reduced pre-ictal activity, and increased the frequency of ictal discharges. Nipecotic acid and NNC-711, both of which block GABA re-uptake, increased population spike amplitude during ictal bursts and promoted the generation of preictal activity. By contrast, addition of ionotropic glutamate-receptor antagonists (NBQX, D-APV) had no consistent effect on ictal burst waveform or frequency and did not fully suppress pre-ictal activity. Similarly, CGP 55848, a GABAB receptor antagonist, has no significant effect on pre-ictal activity or burst frequency (although it did increase burst duration slightly). Our results are consistent with the hypothesis that non-synaptic mechanisms underpin the generation of ictal bursts in CA1 and that GABAA synaptic mechanisms can shape event development by delaying event initiation and counteracting depolarization block.
Analysis and optimization of assembly precision-cost model based on 3D tolerance expression
Authors: Sun Wei , Mu Xiaokai , Sun Qingchao , Sun Zhiyong , Wang Xiaobang 
Published: March 2018

Purpose
This paper aims to comprehensively achieve the requirements of high assembly precision and low cost, a precision-cost model of assembly based on three-dimensional (3D) tolerance is established in this paper.

Design/methodology/approach
The assembly precision is related to the tolerance of parts and the deformation of matching surfaces under load. In this paper, the small displacement torsor (SDT) theory is first utilized to analyze the manufacturing tolerances of parts and the assembly deformation deviation of matching surface. In the meanwhile, the extracting method of SDT parameters is proposed and the assembly precision calculation model based on the 3D tolerance is established. Second, an integrated optimization model based on the machining cost, assembly cost (mapping the deviation domain to the SDT domain) and quality loss cost is built. Finally, the practicability of the precision-cost model is verified by optimizing the horizontal machining center.

Findings
The assembly deviation has a great influence on cost fluctuation. By setting the optimization objective to maximize the assembly precision, the optimal total cost is CNY 72.77, decreasing by 16.83 per cent from the initial value, which meets economical requirements. Meanwhile, the upper bound of each processing tolerance is close to the maximum value of 0.01 mm, indicating that the load deformation can be offset by appropriately increasing the upper bound of the tolerance, but it is necessary to strictly restrict the manufacturing tolerances of lower parts in a reasonable range.

Originality/value
In this paper, a 3D deviation precision-cost model of assembly is established, which can describe the assembly precision more accurately and achieve a lower cost compared with the assembly precision model based on rigid parts.
Does a second-generation returnee make the family firm more entrepreneurial?
Authors: Fu Ying , Si Steven 
Published: March 2018

PurposeThis paper aims to focus on a special group of people in family firms in China, the second generation who are returnees, and to study their impact on family ownership and corporate entrepreneurship.Design/methodology/approachSurvey data from China’s private enterprises in 2015 were used to test the hypotheses. Data were collected through a joint effort by the China Federation of Industry and Commerce and the School of Management of Zhejiang University. The authors used a stratified sampling method, and questionnaires were distributed to 12 provinces in East, Central and West China. Two sets of questionnaires were distributed and answered.FindingsCompared with those family firms without second-generation returnees, the relationship between family ownership and corporate entrepreneurship is significantly enhanced in family firms that have second-generation returnees. Furthermore, compared with the second-generation returnees who stay overseas for a short time, returnees who stay overseas longer are more likely to promote corporate entrepreneurship.Originality/valueThis study explores the unique characteristics of second-generation returnees and explores these returnees’ impact on family ownership and corporate entrepreneurship in the Chinese context. This could generate a new value to the family entrepreneurship literature.
Modularity approach to improve the competitiveness of tourism businesses
Authors: del Vecchio Pasquale , Secundo Giustina , Passiante Giuseppina 
Published: March 2018

PurposeThe purpose of this paper is to contribute to the scientific debate on innovation in tourism by focusing on modularity as emerging approach for creating personalized tourism experiences. The focus on modularity has two objectives. The first is to demonstrate that tourism offering can be conceived as bundles of products and services with growing relevance of knowledge; the second is to highlight how its adoption by tourism firms can enhance their competitiveness and contribute to assuring greater involvement of tourists in co-creating travel experiences.Design/methodology/approachThe study adopts an exploratory approach based on multiple case studies to analyze two innovative tourism companies located in the Apulia region (Southern Italy).FindingsCategorized as integrators of a wide set of tourist products and services, the cases provide a consistent scenario for deepening understanding of the meaning of modularity in tourism.Research limitations/implicationsThe study offers an original contribution in determining the meaning of modularity in the field of knowledge-intensive services by demonstrating that the adoption of a modularity approach in the designing and offering by tourism companies can provide interesting benefits for their competitiveness and the greater satisfaction of customers.Practical implicationsThe study offers implications for companies and decision makers involved in delivering more personalized tourism experiences.Originality/valueElements of originality can be identified in this contribution to the extension of studies on modularity in the service sector as well as for its strategic contribution at the co-creation of personalized tourism experience.
Individual and organizations factors associated with professional quality of life in Florida EMS personnel
Authors: Miller Anastasia , Unruh Lynn , Liu Xinliang , Wharton Tracy , Zhang Ning 
Published: March 2018

Purpose
Personnel who work in emergency medical services (EMS) face work environments which are high stress. These can lead to burnout, secondary traumatic stress (STS), and a reduction of compassion satisfaction (CS). However, very little is known about what individual and work factors influence these negative coping mechanisms in EMS personnel. It is also unknown how perceived organizational and coworker support, debriefing methods, or individual characteristics are associated with the aforementioned coping mechanisms in EMS personnel. The paper aims to discuss these issues.

Design/methodology/approach
A cross-sectional administration of surveys to Florida EMS personnel was done. A total of 351 individuals who regularly performed EMS tasks completed the survey. Three regression analyses were carried out, utilizing the three ProQOL 5 subscales as the dependent variables. The Perceived Coworker Support survey, Survey of Perceived Organizational Support, the Brief Resilience Survey and questions regarding debriefing practices were included.

Findings
Both organizational support and psychological resilience were found to be related to higher CS as well as lower burnout and STS. Coworker support was associated with higher CS. Informal debriefing was associated with higher CS and lower burnout. Several individual factors were also statistically significant, specifically education with CS, being a volunteer and race with burnout, and working part time or volunteering with STS.

Research limitations/implications
There are limitations due to the nature of cross-sectional survey design and due to the sample size. The varying circumstances which EMS personnel work also hinders generalizability.

Originality/value
This study displays statistical relationships between factors which EMS agencies could use to increase employee job satisfaction and potentially reduce turnover.
Integrating sustainability learning outcomes into a university curriculum
Authors: Hill Laura M. , Wang Deane 
Published: March 2018

Purpose
Higher education institutions increasingly have gained momentum in integrating sustainability into university curricula. The purpose of this paper is to elucidate the approval, implementation and management process of the new university-wide, general education requirement in sustainability at the University of Vermont (UVM). The intent is to provide a case study to inform other institutions seeking to create similar university-wide sustainability requirements.

Design/methodology/approach
The authors applied a process framework focused on institutional dynamics and values to analyze UVM’s success in instituting a sustainability requirement across the curriculum. These two frameworks can provide a more general application of this case study to other institutional contexts.

Findings
The case study suggests that in the context of a diverse disciplinary and administrative environment at a university, the strategic unfolding, approval and implementation of UVM’s university-wide, general education sustainability requirement can provide a general model for other universities seeking to embed sustainability across the curriculum.

Originality/value
It is uncommon for research universities with multiple professional schools to offer a university-wide requirement in sustainability. This case study analyzes the creation of a sustainability requirement at UVM by using a process framework to organize the complex, multi-stakeholder activities and events that eventually resulted in a successful curricular change. Thus, it is potentially instructive for institutions seeking to integrate a learning outcomes-based sustainability requirement into a university curriculum because it is generalizable to other institutions and pushes forward our understanding of institutional change.
Strengthening sustainability leadership competencies through university internships
Authors: Meza Rios Maria Margarita , Herremans Irene Marie , Wallace Jean E. , Althouse Norm , Lansdale David , Preusser Manuel 
Published: March 2018

Purpose
This paper aims to determine whether high school students can become agents of change in their local communities by participating in a formal internship program implemented through a partnership between academia (high schools and universities), nonprofit organizations and key community stakeholders.

Design/methodology/approach
Pre- and post-assessments, activity journals and on-line interviews are used to measure the impact of internships on high school students’ sustainability leadership, using a train-the-trainer intervention led by university interns. A conceptual problem-solving framework is proposed and empirically tested to explore the linkages between complex problem constellations, sustainability transition strategies and sustainability visions.

Findings
The five core leadership competencies (systems thinking, strategic, anticipatory, normative and interpersonal) may not be as uniquely discrete as suggested in the literature. An effective learning experience depends on students’ developing competence in their ability to implement a strategic intervention, which is better acquired through hands-on experience rather than a classroom setting.

Practical implications
Students need experiential learning outside of the classroom to make sustainability come alive as a viable option for their communities.

Social implications
The principles of social responsivity, engagement, experiential learning, capacity-building and entrepreneurialism can be executed by transforming the campus into a learning lab, which includes the local community.

Originality/value
This study empirically demonstrates that students need involvement in strategic interventions to imagine and conceptualize sustainability visions. It also shows how academia can help fulfill the United Nations sustainable development goals.
IPO activity and market volatility
Authors: Dicle Mehmet F. , Levendis John 
Published: March 2018

Purpose
The purpose of this paper is to hypothesize two channels in which market volatility affects initial public offering (IPO) activity.

Design/methodology/approach
First, CEOs time the market for IPOs and volatility makes this decision process harder. Second, risk-averse IPO investors become more reluctant toward IPOs during periods of higher volatility for their after-IPO returns.

Findings
The authors provide evidence that higher market volatility leads to lower IPO activity, supporting these hypotheses. More importantly, the authors show that it is not the realized volatility, but rather the implied (expected) volatility, that causes lower IPO activity.

Research limitations/implications
While there may be many companies that are ready to have IPOs, they may be simply waiting for a more opportune time which may not necessarily be a period of high prices but of low volatility.

Practical implications
The public policy prescription is clear: if IPOs are to be encouraged, then regulatory policies should be constructed with the aim of reducing volatility.

Originality/value
This study is the first (to the authors’ knowledge) to argue that it is not the realized volatility which most affects the IPO decisions of executives, entrepreneurs and investors.
Domaine Pas de Choix: government intervention in the Champagne market
Authors: Haight Colleen E. , Wenzel Nikolai G. 
Published: March 2018

PurposeSubsequent to the First World War, the French Government regulated the Champagne industry, and locked the status of protected (and excluded) grapes into the newAppellation d’Origine Contrôléesystem, forever altering the incentives and output of wine producers. The paper aims to discuss these issues.Design/methodology/approachAs a result, some indigenous varietals have disappeared entirely from the region – and a handful remain only in the vineyards and bottles of a few bold entrepreneurs, constituting less than 1 percent of Champagne production.FindingsThe authors assess several traditional explanations (from taste and preferences to agricultural resilience)-and dismiss them as unconvincing. Instead, the authors adopt a public choice framework of regulatory capture to explain the puzzle of thwarted entrepreneurship and consumer choice.Originality/valueThis paper is original.
How to cure cancer: unbinding entrepreneurs in medicine
Authors: Diamond Jr Arthur M. 
Published: March 2018

Purpose
Since the 1960s, experts have predicted that we are on the verge of curing cancer. The purpose of this paper is to explore the obstacles to progress, and to propose policies that will lead more quickly to more success.

Design/methodology/approach
To speed future cures, we need to look at the traits, and methods of those innovative medical entrepreneurs who achieved breakthroughs in the past, and learn what institutions and policies enabled, or blocked, their progress.

Findings
Breakthrough innovators tend to be less-credentialed outsiders who “see what others do not see,” often by nimble and persistent pursuit of serendipitous discoveries or slow hunches. For example, Freireich and DeVita were less-credentialed outsiders. Freireich cured childhood leukemia and DeVita cured Hodgkin’s lymphoma, by pursuing nimble trial-and-error experimentation in their anti-cancer chemotherapy cocktails. Min Chiu Li pursued his slow hunch that his patients would benefit from longer chemotherapy than the mandated National Cancer Institute protocol allowed. He was fired, but his patients were cured. Today, FDA-mandated regulatory protocols, often defended as applications of the precautionary principle, greatly restrict innovative medical entrepreneurs, thereby delaying cancer cures and costing lives.

Originality/value
The paper proposes a new approach to medical innovation, allowing cancer researchers to engage in trial-and-error experiments that follow up on serendipitous discoveries and plausible hunches. The result will be more cures and longer lives.