bluuebunny/crossref_metadata_2025 huggingface dataset:
The Citizen Marketer
Authors: Penney Joel
Published: June 2017

From hashtag activism to the flood of political memes on social media, the landscape of political communication is being transformed by the grassroots circulation of opinion on digital platforms and beyond. The Citizen Marketer offers a new framework for understanding this phenomenon by exploring how everyday people assist in the promotion of political media messages in hopes of persuading their peers and shaping the public mind. The analysis is grounded in the firsthand testimony of citizens who have engaged in popular activities such as changing their profile picture to a protest symbol, tweeting links to news articles to raise strategic awareness about select issues, and publicly displaying everything from slogan T-shirts to viral videos that promote a favored electoral candidate. In contrast to the “slacktivism” critique often leveled at these media-based forms of political activity, The Citizen Marketer argues that they enable citizens to take on the potentially influential role of viral political marketers as they participate in the networked dissemination of ideas. Furthermore, the discussion critically examines the promises of the citizen marketer approach for expanding democratic participation and elevating the voices of marginalized groups, as well as the risks that these practices pose for polarization and partisanship, the trivialization of issues, and control and manipulation by elites. By investigating the logics and motivations behind the citizen marketer, as well as how this approach has developed in response to key social, cultural, and technological changes, the book charts the evolution of activism in the age of mediatized politics, promotional culture, and viral circulation.
Sensorimotor Life
Authors: Di Paolo Ezequiel , Buhrmann Thomas , Barandiaran Xabier
Published: June 2017

This book elaborates a series of contributions to a non–representational theory of action and perception. It is based on current theoretical developments in the enactive approach to life and mind. These enactive ideas are applied and extended to provide a theoretically rich, naturalistic account of sensorimotor meaning and agency.
This account supplies non–representational extensions to the sensorimotor approach to perceptual experience based on the notion of the living body as a self–organizing dynamic system in coupling with the environment. The enactive perspective entails the use of world–involving explanations, in which processes external to an agent co–constitute mental phenomena in ways that cannot be reduced to the supply of information for internal processing.
These contributions to sensorimotor theories are a dynamical–systems description of different types of sensorimotor regularities or sensorimotor contingencies, a dynamical interpretation of Piaget's theory of equilibration to ground the concept of sensorimotor mastery, and a theory of agency as organized networks of sensorimotor schemes, with its implications for sensorimotor subjectivity.
New tools are provided for examining the organization, development, and operation of networks of sensorimotor schemes that compose regional activities and genres of action with their own situated norms. This permits the exploration of new explanations for the phenomenology of agency experience that are favorably contrasted with traditional computational approaches and lead to new empirical predictions. From these proposals, capabilities once beyond the reach of enactive explanations, such as the possibility of virtual actions and the adoption of socially mediated abstract perceptual attitudes, can be addressed.
Desires without Guises
Authors: Döring Sabine A. , Eker Bahadir
Published: June 2017

Evaluativism about desire, the view that desires just are, or necessarily involve, positive evaluations of their objects, currently enjoys widespread popularity in many philosophical circles. This essay argues that evaluativism, in both its doxastic and its perceptual versions, overstates and mischaracterizes the connection between desires and evaluations. Whereas doxastic evaluativism implausibly rules out cases where someone has a desire, despite evaluating its object negatively, being uncertain about its value, or having no doxastic attitude whatsoever toward its evaluative status at all, perceptual evaluativism cannot even properly apply to the large class of standing desires. It is also argued that evaluativism about desire is not even well-motivated in the first place: the theory is supposed to solve a particular puzzle about the role desires play in the explanation of action, yet in fact it does not offer any help whatsoever in dealing with the relevant puzzle.
Building Better Students
Authors: Burrus Jeremy , Mattern Krista , Naemi Bobby D. , Roberts Richard D.
Published: June 2017

The face of the workforce is rapidly changing. Technological advances mean that jobs previously serving as major drivers of the world’s economy are now fully automated. Furthermore, the automatization of many common work activities means that those currently entering the workforce require a different set of skills than those entering the workforce of the 20th century. As such, there is a need to redefine what it means to be “ready to work.” This has led to a major reboot, with new research, applied, and policy questions: How do we define and measure work readiness? How should we prepare students for the workforce? And how can we bridge gaps between college and workforce readiness? A key to reconsidering workforce readiness is placing greater emphasis on measuring and developing noncognitive or “21st century” skills, such as teamwork, creativity, and persistence, and focusing more attention on fostering activities that engage, prepare, and advance students for the future. This volume brings together some of the world’s cutting-edge workforce readiness researchers from the fields of industrial/organizational, educational, and personality psychology to tackle these disparate issues. It concludes with a summary of what has been learned and a set of recommendations for educators, researchers, and policymakers to move the field forward. These recommendations represent a crucial first step to “building better students,” who will truly be ready to work.
Dose escalation via brachytherapy boost for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy and combined chemotherapy
Authors: Chao Hsing-Lung , Liu Shao-Cheng , Tsao Chih-Cheng , Lin Kuen-Tze , Lee Steve P , Lo Cheng-Hsiang , Huang Wen-Yen , Liu Ming-Yueh , Jen Yee-Min , Lin Chun-Shu
Published: June 2017

To investigate if dose escalation using intracavitary brachytherapy (ICBT) improves local control for nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT) and concurrent chemoradiation treatment (CCRT). We retrospectively analyzed 232 patients with Stage T1–3 N0–3 M0 NPC who underwent definitive IMRT with or without additional ICBT boost between 2002 and 2013. For most of the 124 patients who had ICBT boost, the additional brachytherapy was given as 6 Gy in 2 fractions completed within 1 week after IMRT of 70 Gy. CCRT with or without adjuvant chemotherapy was used for 176 patients, including 88 with and 88 without ICBT boost, respectively. The mean follow-up time was 63.1 months. The 5-year overall survival and local control rates were 81.5% and 91.5%, respectively. ICBT was not associated with local control prediction (P = 0.228). However, in a subgroup analysis, 75 T1 patients with ICBT boost had significantly better local control than the other 71 T1 patients without ICBT boost (98.1% vs 85.9%, P = 0.020), despite having fewer patients who had undergone chemotherapy (60.0% vs 76.1%, P = 0.038). Multivariate analysis showed that both ICBT (P = 0.029) and chemotherapy (P = 0.047) influenced local control for T1 patients. Our study demonstrated that dose escalation with ICBT can improve local control of the primary tumor for NPC patients with T1 disease treated with IMRT, even without chemotherapy.
Fuzzy Logic and Mathematics
Authors: Belohlavek Radim , Dauben Joseph W. , Klir George J.
Published: June 2017

The term “fuzzy logic” (FL) is a generic one, which stands for a broad variety of logical systems. Their common ground is the rejection of the most fundamental principle of classical logic—the principle of bivalence—according to which each declarative sentence has exactly two possible truth values—true and false. Each logical system subsumed under FL allows for additional, intermediary truth values, which are interpreted as degrees of truth. These systems are distinguished from one another by the set of truth degrees employed, its algebraic structure, truth functions chosen for logical connectives, and other properties. The book examines from the historical perspective two areas of research on fuzzy logic known as fuzzy logic in the narrow sense (FLN) and fuzzy logic in the broad sense (FLB), which have distinct research agendas. The agenda of FLN is the development of propositional, predicate, and other fuzzy logic calculi. The agenda of FLB is to emulate commonsense human reasoning in natural language and other unique capabilities of human beings. In addition to FL, the book also examines mathematics based on FL. One chapter in the book is devoted to overviewing successful applications of FL and the associated mathematics in various areas of human affairs. The principal aim of the book is to assess the significance of FL and especially its significance for mathematics. For this purpose, the notions of paradigms and paradigm shifts in science, mathematics, and other areas are introduced and employed as useful metaphors.
Modern and Traditional Understandings of Karma
Authors: Goodman Charles
Published: June 2017

Traditional Buddhist views of karma as a cosmic force that makes the universe fair have little credibility in contemporary philosophy. However, a naturalized account of karma, understanding it as a psychological process, could easily turn out to be true. If we read between the lines of Śāntideva’s classic Training Anthology, there is reason to believe that some of his sources already had such a psychological view in mind. A modernized account of karma would have important implications for the theoretical structure of Buddhist ethics, the prospects for a Buddhist political philosophy, and the practice of Engaged Buddhism in contemporary society.
Buddhism without Reincarnation? Examining the Prospects of a “Naturalized” Buddhism
Authors: Westerhoff Jan
Published: June 2017

This essay investigates the feasibility of naturalized Buddhism—in particular a form of Buddhism that rejects reincarnation—by examining the suicide argument. This argument suggests that for the naturalized Buddhist, the result of the Buddhist path, namely escape from the cycle of reincarnation, can be obtained by simply killing oneself, as for the naturalized Buddhist there is not mental continuity after death. The essay examines a variety of ways in which the naturalized Buddhist can respond to the suicide argument and concludes that they are all wanting. It follows that the endeavor of naturalizing Buddhism as it is frequently understood today is fundamentally flawed.
The Power of Race in Cuba
Authors: Clealand Danielle
Published: June 2017

The Power of Race in Cuba analyzes racial ideologies that negate the existence of racism and their effect on racial progress and activism through the lens of Cuba. Since 1959, Fidel Castro and the Cuban government have married socialism and the ideal of racial harmony to create a formidable ideology that is an integral part of Cubans’ sense of identity and their perceptions of race and racism in their country. While the combination of socialism and a colorblind racial ideology is particular to Cuba, strategies that paint a picture of equality of opportunity and deflect the importance of race are not particular to the island’s ideology and can be found throughout the world and in the Americas in particular. By promoting an anti-discrimination ethos, diminishing class differences at the onset of the revolution, and declaring the end of racism, Castro was able to unite belief in the revolution to belief in the erasure of racism. The ideology is bolstered by rhetoric that discourages racial affirmation. The second part of the book examines public opinion on race in Cuba, particularly among black Cubans. It examines how black Cubans have indeed embraced the dominant nationalist ideology that eschews racial affirmation, but also continue to create spaces for black consciousness that challenge this ideology. This work gives a nuanced portrait of black identity in Cuba and through survey data, interviews with formal organizers, and hip-hop artists draws from the many black spaces, both formal and informal, to highlight what black consciousness looks like in Cuba.
The semantics of social relation nouns in Chinese
Authors: Ye Zhengdao
Published: June 2017

This study investigates the nature of Chinese social grouping by analysing the meaning and conceptual structure of a set of nouns that denote salient social relations in Chinese and which form two pairs of complementary opposites. It discusses in detail the commonalities and differences underlying the construals of semantic relation within and between both pairs and offers a semantic method to represent them. The study brings to attention the social categories and associated ways of conceptualizing social and meaning relations that are not often talked about in English, and illustrates that an in-depth analysis of social relation nouns enables researchers to access non-obvious aspects of human social cognition, therefore contributing to a deeper knowledge and understanding of the priorities at play in human social categorization.
Exceptions to the Mirror Principle and morphophonological ‘action at a distance’
Authors: Myler Neil
Published: June 2017

Hyman (2000, 2002) and Kiparsky (2011) have noted that Mirror-Principle-violating morpheme orders often give rise to non-local morphophonological effects. Kiparsky (2011) explicitly argues that this generalization cannot be captured in syntactic approaches to morphology, such as Distributed Morphology. This chapter shows that the generalization can be explained via the combination of two pre-existing tenets of such theories. One is the idea that Vocabulary Insertion proceeds from the most deeply embedded constituent outwards (Bobaljik 2000; Halle and Marantz 1993). The other is the proposal that violations of the Mirror Principle are to be accounted for via phrasal movement of a category containing the lexical root ‘stranding’ one or more affixes (Koopman 2005; Buell 2005; i.a.). The possibility of non-local phonological effects arises because the movements involved in deriving Mirror-Principle-violating orders lead to a disconnect between linear distance from the root and temporal order of Vocabulary Insertion.
What’s the Problem with Symbolic Religious Establishment?
Authors: Lægaard Sune
Published: June 2017

This chapter discusses how religious establishment involves institutional links between state and organized religion. While establishment is often material, it also has symbolic aspects, and sometimes establishment is mainly symbolic. The question we are concerned with here is whether establishment is normatively problematic even when it is purely symbolic. Two accounts, which are present but often not systematically articulated in the literature, for why symbolic establishment might be problematic are presented: the alienation account and the symbolic equality account. These two accounts are importantly different from each other and they face different challenges, which critics of symbolic establishment have to address.
Botulinum Toxin A as an Adjunct to Abdominal Wall Reconstruction for Incisional Hernia
Authors: Soltanizadeh Sinor , Helgstrand Frederik , Jorgensen Lars N.
Published: June 2017

Background:

Repair of large incisional hernias remains a surgical and costly challenge. Temporary paralysis of the lateral abdominal wall muscles with topical administration of botulinum toxin A (BTA) is a new therapeutic concept, which may obviate the need for component separation technique (CST) for repair of large incisional hernias. Current literature on the administration of BTA as adjunct to surgical repair of abdominal incisional hernias was investigated.

Methods:

The electronic databases PubMed and Embase were searched for eligible studies. Two independent investigators evaluated the literature. Data were sought regarding primary fascial closure with and without CST, safety, hernia recurrence, method of application, and preoperative radiological imaging.

Results:

Six cohort studies including a total of 133 patients receiving BTA were identified. No randomized or case–control studies were found. In total, 83.5% of the patients achieved primary fascial closure. Supplemental CST was necessary in 24.1% of the patients. Two patients developed hernia recurrence during follow-up. No postoperative complications or adverse events were considered related to the administration of BTA, except for impairment of postoperative coughing and sneezing. Additionally, radiological imaging showed that BTA increased the length of lateral abdominal muscles before surgery.

Conclusions:

Preoperative administration of BTA increases muscle length and may facilitate primary fascial closure. Optimal administration is at least 2 weeks before repair, whereas the optimal dose of BTA remains to be defined. Carefully designed randomized controlled trials are warranted to identify patients who would benefit from BTA and to eliminate the confounding effect of CST.
A descending pathway facilitates undulatory wave propagation inCaenorhabditis elegansthrough gap junctions
Authors: Xu Tianqi , Huo Jing , Shao Shuai , Po Michelle , Kawano Taizo , Lu Yangning , Wu Min , Zhen Mei , Wen Quan
Published: June 2017

Descending signals from the brain play critical roles in controlling and modulating locomotion kinematics. In theCaenorhabditis elegansnervous system, descending AVB premotor interneurons exclusively form gap junctions with B-type motor neurons that drive forward locomotion. We combined genetic analysis, optogenetic manipulation, and computational modeling to elucidate the function of AVB-B gap junctions during forward locomotion. First, we found that some B-type motor neurons generated intrinsic rhythmic activity, constituting distributed central pattern generators. Second, AVB premotor interneurons drove bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive couplings between neighboring B-type motor neurons entrained the frequency of body oscillators, forcing coherent propagation of bending waves. Despite substantial anatomical differences between the worm motor circuit and those in higher model organisms, we uncovered converging principles that govern coordinated locomotion.

Significance Statement

A deep understanding of the neural basis of motor behavior must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. Here, we report on an integrative approach to defining the circuit logic underlying coordinated locomotion inC. elegans.Our combined experimental and computational analysis revealed that (1) motor neurons inC. eleganscould function as intrinsic oscillators; (2) Descending inputs and proprioceptive couplings work synergistically to facilitate the sequential activation of motor neuron activities, allowing bending waves to propagate efficiently along the body. Our work thus represents a key step towards an integrative view of animal locomotion.
EsaB is a core component of theStaphylococcus aureusType VII secretion system
Authors: Guillermina Casabona M. , Buchanan Grant , Zoltner Martin , Harkins Catriona P. , Holden Matthew T.G. , Palmer Tracy
Published: June 2017

Type VII secretion systems (T7SS) are found in many bacteria and secrete proteins involved in virulence and bacterial competition. InStaphylococcus aureusthe small ubiquitin-like EsaB protein has been previously implicated as having a regulatory role in the production of the EsxC substrate. Here we show that in theS. aureusRN6390 strain, EsaB does not genetically regulate production of any T7 substrates or components, but is indispensable for secretion activity. Consistent with EsaB being a core component of the T7SS, loss of either EsaB or EssC are associated with upregulation of a common set of iron acquisition genes. However, a further subset of genes were dysregulated only in the absence of EsaB. In addition, fractionation revealed that although an EsaB fusion to yellow fluorescent protein partially localised to the membrane, it was still membrane-localised when the T7SS was absent. Taken together our findings suggest that EsaB has T7SS-dependent and T7SS-independent roles inS. aureus.
Astrin-SKAP complex reconstitution reveals its kinetochore interaction with microtubule-bound Ndc80
Authors: Kern David M. , Wilson-Kubalek Elizabeth M. , Cheeseman Iain M.
Published: June 2017

Chromosome segregation requires robust interactions between the macromolecular kinetochore structure and dynamic microtubule polymers. A key outstanding question is how kinetochore-microtubule attachments are modulated to ensure that bi-oriented attachments are selectively stabilized and maintained. The Astrin-SKAP complex localizes preferentially to properly bi-oriented sister kinetochores, representing the final outer kinetochore component recruited prior to anaphase onset. Here, we reconstitute the 4-subunit Astrin-SKAP complex, including a novel MYCBP subunit. Our work demonstrates that the Astrin-SKAP complex contains separable kinetochore localization and microtubule binding domains. In addition, through cross-linking analysis in human cells and biochemical reconstitution, we show that the Astrin-SKAP complex binds synergistically to microtubules with the Ndc80 complex, the core component of the kinetochore-microtubule interface, to form an integrated interface. We propose a model in which the Astrin-SKAP complex acts together with the Ndc80 complex to stabilize correctly formed kinetochore-microtubule interactions.
Differential roles of sleep spindles and sleep slow oscillations in memory consolidation
Authors: Wei Yina , Krishnan Giri P , Komarov Maxim , Bazhenov Maxim
Published: June 2017

Sleep plays an important role in consolidation of recent memories. However, the mechanisms of consolidation remain poorly understood. In this study, using a realistic computational model of the thalamocortical network, we demonstrated that sleep spindles (the hallmark of N2 stage sleep) and slow oscillations (the hallmark of N3 stage sleep) both facilitate spike sequence replay as necessary for consolidation. When multiple memories were trained, the local nature of spike sequence replay during spindles allowed replay of the memories independently, while during slow oscillations replay of the weak memory was competing to the strong memory replay. This led to the weak memory extinction unless when sleep spindles (N2 sleep) preceded slow oscillations (N3 sleep), as observed during natural sleep. Our study presents a mechanistic explanation for the role of sleep rhythms in memory consolidation and proposes a testable hypothesis how the natural structure of sleep stages provides an optimal environment to consolidate memories.

Significant Statement

Numerous studies suggest importance of NREM sleep rhythms – spindles and slow oscillations - in sleep related memory consolidation. However, synaptic mechanisms behind the role of these rhythms in memory and learning are still unknown. Our new study predicts that sleep replay - the neuronal substrate of memory consolidation - is organized within the sleep spindles and coordinated by the Down to Up state transitions of the slow oscillation. For multiple competing memories, slow oscillations facilitated only strongest memory replay, while sleep spindles allowed a consolidation of the multiple competing memories independently. Our study predicts how the basic structure of the natural sleep stages provides an optimal environment for consolidation of multiple memories.
Live-cell mapping of organelle-associated RNAs via proximity biotinylation combined with protein-RNA crosslinking
Authors: Kaewsapsak Pornchai , Shechner David M. , Mallard William , Rinn John L. , Ting Alice Y.
Published: June 2017

The spatial organization of RNA within cells is a crucial factor in a wide range of biological functions, spanning all kingdoms of life. However, a general understanding of RNA localization has been hindered by a lack of simple, high-throughput methods for mapping the transcriptomes of subcellular compartments. Here, we develop such a method, termed APEX-RIP, which combines peroxidase-catalyzed, spatially restricted in situ protein biotinylation with RNA-protein chemical crosslinking. We demonstrate that, using a single protocol, APEX-RIP can isolate RNAs from a variety of subcellular compartments, including the mitochondrial matrix, nucleus, bulk cytosol, and endoplasmic reticulum (ER), with higher specificity and coverage than do conventional approaches. We furthermore identify candidate RNAs localized to mitochondria-ER junctions and nuclear lamina, two compartments that are recalcitrant to classical biochemical purification. Since APEX-RIP is simple, versatile, and does not require special instrumentation, we envision its broad application in a variety of biological contexts.
Spatial inequality and dynamics of foreign hypermarket retailers in China
Authors: Zhang Ling , Wei Yehua Dennis
Published: June 2017

The globalisation of retailing has intensified since the mid‐1990s with the rise of a group of international retailers. Foreign retailers have greatly impacted the Chinese retail market since the opening up of the retail sector in 1992. This study aims to examine spatial inequality and dynamics of foreign hypermarket retailers at different geographic scales in China. Although the relative gaps in foreign hypermarkets among Chinese regions are narrowing, the absolute gaps are widening. Logistic regression models are used to identify locational determinants of foreign retailers Carrefour, Wal‐Mart, and RT‐Mart at the intercity level. Carrefour prefers cities with larger urban district populations, longer time of being open to international retailers, and more foreign investment. While urban district populations are significant to Wal‐Mart and RT‐Mart as well, they favour cities where people have higher annual salaries and aim to achieve internal economies of scale at the provincial level. The three leading foreign retailers also have different first‐city and city size preferences in their provincial expansions.
Methylation of the ribosomal RNA gene promoter is associated with aging and age‐related decline
Authors: D'Aquila Patrizia , Montesanto Alberto , Mandalà Maurizio , Garasto Sabrina , Mari Vincenzo , Corsonello Andrea , Bellizzi Dina , Passarino Giuseppe
Published: June 2017

The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age‐related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20‐ to 105‐year‐old humans and in different tissues (blood, heart, liver, kidney, and testis) of 15 rats 3–96 weeks old. In humans, we did not find a consistently significant correlation between CpG site methylation and chronological age. Furthermore, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9‐year follow‐up study. We consistently confirmed such result in a replication sample. In rats, the analysis of the homologous region in the tissues revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with observed methylation patterns, with a lower expression of rRNA in highly methylated samples. As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNA may represent a potential biomarker of aging.
Talking to healthcare providers about sex in later life: Findings from a qualitative study with older Australian men and women
Authors: Fileborn Bianca , Lyons Anthony , Heywood Wendy , Hinchliff Sharron , Malta Sue , Dow Briony , Brown Graham , Barrett Catherine , Minichiello Victor
Published: June 2017

Objective

Healthcare providers (HCPs) can play an important role in supporting the sexual health of older adults; however, we know little about the experiences of older people in talking to HCPs about sex. This article examines older adults' experiences and perceptions of talking to HCPs about sex.

Methods

Semi‐structured interviews were conducted with 30 men and 23 women aged 60 and older recruited from a national, online survey of older Australians. Data were analysed using a thematic approach.

Results

Most participants did not discuss sex with their HCP, and their HCP did not raise it. For those who did discuss sex with a HCP, negative and stigmatising responses were common. Positive responses could facilitate access to sexual health care.

Conclusion

Older people benefit when HCPs are proactive and ask about sexual health. Education in how to talk about sex with older people would also be beneficial for HCPs.
Is it right to ignore learning‐curve patients? Laparoscopic colorectal trials
Authors: Meagher Alan P. , Yang Shi , Li Shuyuan
Published: June 2017

Background

Increasingly complex, technically demanding surgical procedures utilizing emerging technologies have developed over recent decades and are recognized as having long ‘learning curves’. This raises significant new issues. Ethically and scientifically, the outcome of a patient in the learning curve is as important as the outcome of a patient outside the learning curve. The aim of this study is to highlight just one aspect of our approach to learning‐curve patients that should change.

Methods

The protocols of multicentre, prospective, randomized trials of patients undergoing either traditional open or laparoscopic surgery for colorectal cancer were reviewed. The number of patients excluded from the published trial results because they were in surgeons’ learning curves was calculated. The seven editorials accompanying these publications were also examined for any mention of these patients.

Results

The eight studies identified had similar designs. All patients in the surgeons’ laparoscopic learning curves, which were often several years long, were excluded from the actual trials. The total number of patients included in the trial publications was 5680. The number of patients excluded because they were in the surgeons’ laparoscopic learning curves was >10 605. In none of the studies or accompanying editorials is there any mention of the total number of patients in the surgeons’ learning curves, these patients’ outcomes or how inclusion of their outcomes might have affected the overall results.

Conclusion

Learning curves are inescapable in modern medicine. Our recognition of patients in these curves should evolve, with more data about them included in trial publications.
Mapping the allosteric sites of the A2A adenosine receptor
Authors: Caliman Alisha D. , Miao Yinglong , McCammon James A.
Published: June 2017

The A2A adenosine receptor (A2AAR) is a G protein‐coupled receptor that is pharmacologically targeted for the treatment of inflammation, sepsis, cancer, neurodegeneration, and Parkinson's disease. Recently, we applied long‐timescale molecular dynamics simulations on two ligand‐free receptor conformations, starting from the agonist‐bound (PDB ID: 3QAK) and antagonist‐bound (PDB ID: 3EML) X‐ray structures. This analysis revealed four distinct conformers of the A2AAR: the active, intermediate 1, intermediate 2, and inactive. In this study, we apply the fragment‐based mapping algorithm, FTMap, on these receptor conformations to uncover five non‐orthosteric sites on the A2AAR. Two sites that are identified in the active conformation are located in the intracellular region of the transmembrane helices (TM) 3/TM4 and the G protein‐binding site in the intracellular region between TM2/TM3/TM6/TM7. Three sites are identified in the intermediate 1 and intermediate 2 conformations, annexing a site in the lipid interface of TM5/TM6. Five sites are identified in the inactive conformation, comprising a site in the intracellular region of TM1/TM7 and in the extracellular region of TM3/TM4 of the A2AAR. We postulate that these sites on the A2AAR be screened for allosteric modulators for the treatment of inflammatory and neurological diseases.
Using analytic morphomics to describe body composition associated with post‐kidney transplantation diabetes mellitus
Authors: Cron David C. , Noon Kelly A. , Cote Devan R. , Terjimanian Michael N. , Augustine Joshua J. , Wang Stewart C. , Englesbe Michael J. , Woodside Kenneth J.
Published: June 2017

Background

Better risk assessment tools are needed to predict post‐transplantation diabetes mellitus (PTDM). Using analytic morphomic measurements from computed tomography (CT) scans, we aimed to identify specific measures of body composition associated with PTDM.

Methods

We retrospectively reviewed 99 non‐diabetic kidney transplant recipients who received pre‐transplant CT scans at a single institution between 1/2005 and 5/2014. Analytic morphomic techniques were used to measure abdominal adiposity, abdominal size, and psoas muscle area and density, standardized by gender. We measured the associations of these morphomic factors with PTDM.

Results

One‐year incidence of PTDM was 18%. The morphomic factors significantly associated with PTDM included visceral fat area (OR=1.84 per standard deviation increase, P=.020), body depth (OR=1.79, P=.035), and total body area (OR=1.67, P=.049). Clinical factors significantly associated with PTDM included African American race (OR=3.01, P=.044), hypertension (OR=2.97, P=.041), and dialysis vintage (OR=1.24 per year on dialysis, P=.048). Body mass index was not associated with PTDM (OR=1.05, P=.188). On multivariate modeling, visceral fat area was an independent predictor of PTDM (OR=1.91, P=.035).

Conclusions

Analytic morphomics can identify pre‐transplant measurements of body composition that are predictive of PTDM in kidney transplant recipients. Pre‐transplant imaging contains a wealth of underutilized data that may inform PTDM prevention strategies.
Two zinc finger proteins from Mycobacterium smegmatis: DNA binding and activation of transcription
Authors: Ghosh Subho , Chatterji Dipankar
Published: June 2017

Single zinc finger domain containing proteins are very few in number. Of numerous zinc finger proteins in eukaryotes, only three of them like GAGA, Superman and DNA binding by one finger (Dof) have single zinc finger domain. Although few zinc finger proteins have been described in eubacteria, no protein with single C4 zinc finger has been described in details in anyone of them. In this article, we are describing two novel C‐terminal C4 zinc finger proteins—Msmeg_0118 and Msmeg_3613 from Mycobacterium smegmatis. We have named these proteins as Mszfp1 (Mycobacterial Single Zinc Finger Protein 1) and Mszfp2 (Mycobacterial Single Zinc Finger Protein 2). Both the proteins are expressed constitutively, can bind to DNA and regulate transcription. It appears that Mszfp1 and Mszfp2 may activate transcription by interacting with RNA polymerase.
Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination
Authors: Takeuchi Miki , Inoue Chikako , Goshima Akiko , Nagao Yusuke , Shimizu Koichi , Miyamoto Hiroki , Shimizu Takashi , Hashimoto Hisashi , Yonemura Shigenobu , Kawahara Atsuo , Hirata Yutaka , Yoshida Masayuki , Hibi Masahiko
Published: June 2017

A spontaneous medaka ro mutant shows abnormal wobbling and rolling swimming behaviors. By positional cloning, we mapped the ro locus to a region containing the gene encoding Contactin1b (Cntn1b), which is an immunoglobulin (Ig)‐superfamily domain‐containing membrane‐anchored protein. The ro mutant had a deletion in the cntn1b gene that introduced a premature stop codon. Furthermore, cntn1b mutants generated by the CRISPR/Cas9 system and trans‐heterozygotes of the CRISPR mutant allele and ro had abnormal swimming behavior, indicating that the cntn1b gene was responsible for the ro‐mutant phenotype. We also established zebrafish cntn1a and cntn1b mutants by transcription activator‐like effector nucleases (TALENs). Zebrafish cntn1b but not cntn1a mutants showed abnormal swimming behaviors similar to those in the ro mutant, suggesting that Cntn1b plays a conserved role in the formation or function of the neural circuits that control swimming in teleosts. Although Cntn1‐deficient mice have abnormal cerebellar neural circuitry, there was no apparent histological abnormality in the cerebellum of medaka or zebrafish cntn1b mutants. The medaka cntn1b mutants had defective optokinetic response (OKR) adaptation and abnormal rheotaxis (body positioning relative to water flow). Medaka and zebrafish cntn1b mutants are effective models for studying the neural circuits involved in motor learning and motor coordination.
Estimating the potential cost of a high dose immune tolerance induction (ITI) therapy relative to the cost of a combined therapy of a low dose ITI therapy with bypassing agent prophylaxis
Authors: Kenet G. , Oladapo A. , Epstein J.D. , Thompson C. , Novack A. , Nugent D. J.
Published: June 2017

Introduction

The International Immune Tolerance Study (I‐ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time‐to‐treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI.

Aim and Methods

An economic model was developed to compare high dose ITI to low dose ITI with BAP. All model inputs were derived from clinical trials. The I‐ITI study indicated a median time to negative inhibitor titre of 4.6 and 9.2 months and average number of bleeds/patient of 4.2 and 9.9 for the high and low dose regimens respectively. Based on the BAP trials, aPCC (85 U/kg/TIW) and rFVIIa (90 μg/kg/day) achieved a 62% and 45% reduction in bleeding frequency respectively. Cost analysis was from a US third party payer perspective and limited to drug costs. One‐way, two‐way and probabilistic sensitivity analyses were performed.

Results

Costs of low dose ITI with aPCC prophylaxis until negative inhibitor titre is achieved was 24.0% less compared to high dose ITI. Low dose ITI with rFVIIa prophylaxis cost 46.5% more compared to high dose ITI. Model results were robust in the majority of the sensitivity analyses.

Conclusion

A low dose ITI regimen with aPCC prophylaxis may be cost saving compared to a high dose ITI regimen with the potential to reduce morbidity by lowering the risk for breakthrough bleeds.
Taste perception and purchase intent of oil‐in‐water spreads: effects of oil types and salt (NaCl or KCl) concentrations
Authors: Cerrato Rodriguez Wilfredo Alejandro , Torrico Damir Dennis , Osorio Luis Fernando , Cardona Jorge , Prinyawiwatkul Witoon
Published: June 2017

Associations of sodium intake with heart‐related problems are creating awareness towards reducing sodium. Potassium chloride (KCl), a substitute for sodium chloride (NaCl), has the disadvantage of imparting bitterness at high concentrations. We evaluated physical characteristics, taste perception and purchase intent of KCl and NaCl in oil‐in‐water spreads/emulsions composed by olive, rice bran and soya bean oils. Consumers (N = 300) evaluated saltiness/bitterness of emulsions prepared with 65% oil, and NaCl (0.5% and 1.0%) or KCl (0.75% and 1.5%). Olive oil spreads (104.07–107.43 Pa s) had higher viscosity compared to other spreads (59.16–74.96 Pa s). Type of oil had significant effects on bitterness, overall taste liking and viscosity. Taste liking decreased due to bitterness of olive oil spreads (mean drop=1.72–2.43). Purchase intent was positively associated with saltiness and pH and increased with oil claims (increase = 1.3%–22.1%) compared to sodium claims (increase = 0.0%–12.9%). These findings are useful for understanding taste perception of emulsions.
Chemical composition, cooking quality, texture and consumer acceptance of pasta with Eruca vesicaria leaves
Authors: Bouacida Saoussen , Ben Amira Amal , Ben Haj Koubaier Hayet , Blecker Christophe , Bouzouita Nabiha
Published: June 2017

In this study, pasta with dried Eruca vesicaria leaves commonly known as Rocket salad and spinach leaves flours were prepared. Samples were evaluated for its chemical composition, cooking quality, textural, colour and consumer acceptance. Results showed that pasta with Eruca vesicaria had the highest dietary fibre content (5.30–9.50 g/100 g) and the lowest fat content (2.13–2.80 g/100 g). The optimally cooked pasta with 5% of leaves (stored 30 days) and pasta with 10% of leaves (stored 14 days) have good cooking quality with cooking loss ≤8%. The green colour and textural characteristics of pastas were stable during all period at 4 °C. Textural characteristics of pasta with rocket and spinach were similar. Pasta with 10% of rocket leaves has presented the highest overall acceptability score.
A single‐tube flow cytometric procedure for enhancing the diagnosis and prognostic classification of patients with myelodysplastic syndromes
Authors: Kárai B. , Bedekovics J. , Miltényi Zs. , Gergely L. , Szerafin L. , Ujfalusi A. , Kappelmayer J. , Hevessy Zs.
Published: June 2017

Introduction

We created a simple and effective flow cytometry scoring system (FCSS) for suspected Myelodysplastic syndromes (MDS) samples and evaluated its diagnostic and prognostic potential.

Methods

Besides evaluating the four parameters suggested by Ogata, we investigated erythroid precursors and mast cells. We evaluated the six‐parameterFCSSin a four‐color setting (test cohort: 51 patients; 25 controls), then we implemented it into an eight‐color setting and tested it on a validation cohort of patients withMDS(n=31).

Results

When we comparedMDScases to non‐MDSsamples in the test cohort, we detected significant differences regarding not only the four major parameters but also two additional ones, namelyCD71rCV% of erythroid precursors (P=.004) and mast cell percentage (MC%) (P=.001). The utilization of the modified six‐parameterFCSSprovided high sensitivity and specificity both in the four color (84% and 80%, respectively) and in the eight color (81% and 100%, respectively) setting, with an excellent discriminative power betweenMDSand non‐MDSsamples. Furthermore, we found significant difference in event‐free survival between the risk groups based on the modified six‐parameterFCSS(P=.001).

Conclusion

We evaluated and validated a single‐tube flow cytometric procedure for a simple six‐parameterFCSSwhich has not only high diagnostic but also prognostic power.
Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells
Authors: Boudousquie Caroline , Bossi Giovanna , Hurst Jacob M. , Rygiel Karolina A. , Jakobsen Bent K. , Hassan Namir J.
Published: June 2017

The success of immune system‐based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilizing monoclonal T cell receptors (TCRs) against cancer (ImmTAC™ molecules: fusion proteins consisting of a soluble, affinity enhanced TCR and an anti‐CD3 scFv antibody) were previously shown to redirect CD8+ and CD4+ T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognizing a peptide derived from the melanoma‐specific protein, gp100, presented by HLA‐A*0201) efficiently redirects and activates effector and memory cells from both CD8+ and CD4+ repertoires. Using isolated subpopulations of T cells, we find that both terminally differentiated and effector memory CD8+ T cells redirected by IMCgp100 are potent killers of melanoma cells. Furthermore, CD4+ effector memory T cells elicit potent cytotoxic activity leading to melanoma cell killing upon redirection by IMCgp100. The majority of T cell subsets belonging to both the CD8+ and CD4+ repertoires secrete key pro‐inflammatory cytokines (tumour necrosis factor‐α, interferon‐γ, interleukin‐6) and chemokines (macrophage inflammatory protein‐1α‐β, interferon‐γ‐inducible protein‐10, monocyte chemoattractant protein‐1). At an individual cell level, IMCgp100‐redirected T cells display a polyfunctional phenotype, which is a hallmark of a potent anti‐cancer response. This study demonstrates that IMCgp100 induces broad immune responses that extend beyond the induction of CD8+ T cell‐mediated cytotoxicity. These findings are of particular importance because IMCgp100 is currently undergoing clinical trials as a single agent or in combination with check point inhibitors for patients with malignant melanoma.
Ischemia‐responsive protein 94 is a key mediator of ischemic neuronal injury‐induced microglial activation
Authors: Tikamdas Rajiv , Singhal Sarthak , Zhang Ping , Smith Justin A. , Krause Eric G. , Stevens Stanley M. , Song Sihong , Liu Bin
Published: June 2017

Neuroinflammation, especially activation of microglia, the key immune cells in the brain, has been proposed to contribute to the pathogenesis of ischemic stroke. However, the dynamics and the potential mediators of microglial activation following ischemic neuronal injury are not well understood. In this study, using oxygen/glucose deprivation and reoxygenation with neuronal and microglial cell cultures as an in vitro model of ischemic neuronal injury, we set out to identify neuronal factors released from injured neurons that are capable of inducing microglial activation. Conditioned media (CM) from hippocampal and cortical neurons exposed to oxygen/glucose deprivation and reoxygenation induced significant activation of microglial cells as well as primary microglia, evidenced by up‐regulation of inducible nitric oxide synthase, increased production of nitrite and reactive oxygen species, and increased expression of microglial markers. Mechanistically, neuronal ischemia‐responsive protein 94 (Irp94) was a key contributor to microglial activation since significant increase in Irp94 was detected in the neuronal CM following ischemic insult and immunodepletion of Irp94 rendered ischemic neuronal CM ineffective in inducing microglial activation. Ischemic insult‐augmented oxidative stress was a major facilitator of neuronal Irp94 release, and pharmacological inhibition of NADPH oxidase significantly reduced the ischemic injury–induced neuronal reactive oxygen species production and Irp94 release. Taken together, these results indicate that neuronal Irp94 may play a pivotal role in the propagation of ischemic neuronal damage. Continued studies may help identify Irp94 and/or related proteins as potential therapeutic targets and/or diagnostic/prognostic biomarkers for managing ischemia‐associated brain disorders.

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