bluuebunny/crossref_metadata_2025 huggingface dataset:
Racing the Beam
Authors: Montfort Nick , Bogost Ian
Published: December 2018

A study of the relationship between platform and creative expression in the Atari VCS.

The Atari Video Computer System dominated the home video game market so completely that “Atari” became the generic term for a video game console. The Atari VCS was affordable and offered the flexibility of changeable cartridges. Nearly a thousand of these were created, the most significant of which established new techniques, mechanics, and even entire genres. This book offers a detailed and accessible study of this influential video game console from both computational and cultural perspectives.

Studies of digital media have rarely investigated platforms—the systems underlying computing. This book (the first in a series of Platform Studies) does so, developing a critical approach that examines the relationship between platforms and creative expression. Nick Montfort and Ian Bogost discuss the Atari VCS itself and examine in detail six game cartridges: Combat, Adventure, Pac-Man, Yars' Revenge, Pitfall!, and Star Wars: The Empire Strikes Back. They describe the technical constraints and affordances of the system and track developments in programming, gameplay, interface, and aesthetics. Adventure, for example, was the first game to represent a virtual space larger than the screen (anticipating the boundless virtual spaces of such later games as World of Warcraft and Grand Theft Auto), by allowing the player to walk off one side into another space; and Star Wars: The Empire Strikes Back was an early instance of interaction between media properties and video games. Montfort and Bogost show that the Atari VCS—often considered merely a retro fetish object—is an essential part of the history of video games.
Our Own Worst Enemy?
Authors: Weiner Sharon K.
Published: December 2018

An examination of the effectiveness of knowledge nonproliferation programs implemented by the United States after the fall of the Soviet Union.

When the Soviet Union collapsed in 1991, many observers feared that terrorists and rogue states would obtain weapons of mass destruction (WMD) or knowledge about how to build them from the vast Soviet nuclear, biological, and chemical weapons complex. The United States launched a major effort to prevent former Soviet WMD experts, suddenly without salaries, from peddling their secrets. In Our Own Worst Enemy, Sharon Weiner chronicles the design, implementation, and evolution of four U.S. programs that were central to this nonproliferation policy and assesses their successes and failures. Weiner examines the parlous state of the former Soviet nuclear, biological, and chemical weapons complex, the contentious domestic political debate within the United States, and most critically, the institutional interests and dynamics of the Defense, State, and Energy departments, which were charged with preventing the spread of WMD expertise. She explains why—despite unprecedented cooperation between the former Cold War adversaries—U.S. nonproliferation programs did not succeed at redirecting or converting to civilian uses significant parts of the former Soviet weapons complex. She shows how each of the U.S. government bureaucracies responsible for managing vital nonproliferation policies let its own organizational interests trump U.S. national security needs. Our Own Worst Enemy? raises important and troubling questions for anyone interested in understanding and improving policymaking and implementation processes in the area of nonproliferation and in U.S. national security policy more generally.
Arguments that Count
Authors: Slayton Rebecca
Published: December 2018

How differing assessments of risk by physicists and computer scientists have influenced public debate over nuclear defense.

In a rapidly changing world, we rely upon experts to assess the promise and risks of new technology. But how do these experts make sense of a highly uncertain future? In Arguments that Count, Rebecca Slayton offers an important new perspective. Drawing on new historical documents and interviews as well as perspectives in science and technology studies, she provides an original account of how scientists came to terms with the unprecedented threat of nuclear-armed intercontinental ballistic missiles (ICBMs). She compares how two different professional communities—physicists and computer scientists—constructed arguments about the risks of missile defense, and how these arguments changed over time. Slayton shows that our understanding of technological risks is shaped by disciplinary repertoires—the codified knowledge and mathematical rules that experts use to frame new challenges. And, significantly, a new repertoire can bring long-neglected risks into clear view.

In the 1950s, scientists recognized that high-speed computers would be needed to cope with the unprecedented speed of ICBMs. But the nation's elite science advisors had no way to analyze the risks of computers so used physics to assess what they could: radar and missile performance. Only decades later, after establishing computing as a science, were advisors able to analyze authoritatively the risks associated with complex software—most notably, the risk of a catastrophic failure. As we continue to confront new threats, including that of cyber attack, Slayton offers valuable insight into how different kinds of expertise can limit or expand our capacity to address novel technological risks.
Alien Agency
Authors: Salter Chris
Published: December 2018

An investigation into what happens in creative practice when the materials of art and research behave and perform in ways beyond the creators' intentions.

In Alien Agency, Chris Salter tells three stories of art in the making. Salter examines three works in which the materials of art—the “stuff of the world”—behave and perform in ways beyond the creator's intent, becoming unknown, surprising, alien. Studying these works—all three deeply embroiled in and enabled by science and technology—allows him to focus on practice through the experiential and affective elements of creation. Drawing on extensive ethnographic observation and on his own experience as an artist, Salter investigates how researcher-creators organize the conditions for these experimental, performative assemblages—assemblages that sidestep dichotomies between subjects and objects, human and nonhuman, mind and body, knowing and experiencing.

Salter reports on the sound artists Bruce Odland and Sam Auinger (O+A) and their efforts to capture and then project unnoticed urban sounds; tracks the multi-year project TEMA (Tissue Engineered Muscle Actuators) at the art research lab SymbioticA and its construction of a hybrid “semi-living” machine from specially grown mouse muscle cells; and describes a research-creation project (which he himself initiated) that uses light, vibration, sound, smell, and other sensory stimuli to enable audiences to experience other cultures' “ways of sensing.” Combining theory, diary, history, and ethnography, Salter also explores a broader question: How do new things emerge into the world and what do they do?
Changing Lanes
Authors: DiMento Joseph F.C. , Ellis Cliff
Published: December 2018

The story of the evolution of the urban freeway, the competing visions that informed it, and the emerging alternatives for more sustainable urban transportation.

Urban freeways often cut through the heart of a city, destroying neighborhoods, displacing residents, and reconfiguring street maps. These massive infrastructure projects, costing billions of dollars in transportation funds, have been shaped for the last half century by the ideas of highway engineers, urban planners, landscape architects, and architects—with highway engineers playing the leading role. In Changing Lanes, Joseph DiMento and Cliff Ellis describe the evolution of the urban freeway in the United States, from its rural parkway precursors through the construction of the interstate highway system to emerging alternatives for more sustainable urban transportation.

DiMento and Ellis describe controversies that arose over urban freeway construction, focusing on three cases: Syracuse, which early on embraced freeways through its center; Los Angeles, which rejected some routes and then built I-105, the most expensive urban road of its time; and Memphis, which blocked the construction of I-40 through its core. Finally, they consider the emerging urban highway removal movement and other innovative efforts by cities to re-envision urban transportation.
Bleak Houses
Authors: Brittain-Catlin Timothy J.
Published: December 2018

Why some architects fail to realize their ideal buildings, and what architecture critics can learn from novelists.

The usual history of architecture is a grand narrative of soaring monuments and heroic makers. But it is also a false narrative in many ways, rarely acknowledging the personal failures and disappointments of architects. In Bleak Houses, Timothy Brittain-Catlin investigates the underside of architecture, the stories of losers and unfulfillment often ignored by an architectural criticism that values novelty, fame, and virility over fallibility and rejection.

As architectural criticism promotes increasingly narrow values, dismissing certain styles wholesale and subjecting buildings to a Victorian litmus test of “real” versus “fake,” Brittain-Catlin explains the effect this superficial criticality has had not only on architectural discourse but on the quality of buildings. The fact that most buildings receive no critical scrutiny at all has resulted in vast stretches of ugly modern housing and a pervasive public illiteracy about architecture.
Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos
Authors: Mir Mustafa , Stadler Michael R , Ortiz Stephan A , Hannon Colleen E , Harrison Melissa M , Darzacq Xavier , Eisen Michael B
Published: December 2018

The regulation of transcription requires the coordination of numerous activities on DNA, yet how transcription factors mediate these activities remains poorly understood. Here, we use lattice light-sheet microscopy to integrate single-molecule and high-speed 4D imaging in developing Drosophila embryos to study the nuclear organization and interactions of the key transcription factors Zelda and Bicoid. In contrast to previous studies suggesting stable, cooperative binding, we show that both factors interact with DNA with surprisingly high off-rates. We find that both factors form dynamic subnuclear hubs, and that Bicoid binding is enriched within Zelda hubs. Remarkably, these hubs are both short lived and interact only transiently with sites of active Bicoid-dependent transcription. Based on our observations, we hypothesize that, beyond simply forming bridges between DNA and the transcription machinery, transcription factors can organize other proteins into hubs that transiently drive multiple activities at their gene targets.

Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Traditional and cyber bullying and sexual harassment: A longitudinal assessment of risk and protective factors
Authors: Leemis Ruth W. , Espelage Dorothy L. , Basile Kathleen C. , Mercer Kollar Laura M. , Davis Jordan P.
Published: December 2018

Adolescents engage in bullying and sexual harassment perpetration both in‐person and online. Yet, little is known about the overlap of traditional (in‐person) and cyber bullying and sexual harassment perpetration. The present study assessed the co‐occurrence of these forms of aggression in high school and identified middle school predictors based on participants’ perceptions of factors across the social ecology. Racially diverse middle and high school students (n = 3549) were surveyed over four time points from Spring 2008 to Spring 2013. A latent class analysis was used to identify classes of individuals according to endorsement of traditional and cyber bullying and sexual harassment items in high school. Four classes were identified: (1) high all, consisting of traditional and cyber bullying and sexual harassment perpetration (n = 227); (2) traditional bullying perpetration (n = 604); (3) traditional and cyber bullying perpetration (n = 450); and (4) low all (n = 1,261). Students who reported high levels of anger, self‐esteem, empathy, pornographic exposure, and traditional masculinity (individual level), lower levels of social support and parental monitoring (relational level), and higher levels of school belonging (community level) had increased odds of being in the high all class when compared to the other classes. Given the co‐occurrence of traditional and cyber bullying and sexual harassment, prevention programming that addresses both forms of aggression across traditional and online contexts may be beneficial. This study also suggests the importance of comprehensive prevention efforts that incorporate approaches at the different ecological levels, such as teaching adolescents healthy emotional and interpersonal skills, and engaging parents in prevention.
Editorial: Harmful or helpful to learning? The impact of seductive details on learning and instruction
Authors: Eitel Alexander , Kühl Tim
Published: December 2018

Most previous research found negative effects on learning outcomes when interesting but irrelevant information (i.e., seductive details) is added to an instruction. To what degree such effects are bound to specific conditions is in the focus of this special issue. Specifically, 11 empirical studies are reported within this special issue. They all address the topic of seductive details in learning and instruction by focusing either on cognitive moderators (e.g., working memory capacity and current beliefs) or on noncognitive moderators (e.g., arousal and affect) of the seductive details effect. Taken together, results from the empirical studies hint towards new moderators and suggest that the negative effects of seductive details on learning outcomes may be smaller than expected based on previous research.
Understanding the weapon focus effect: The role of threat, unusualness, exposure duration, and scene complexity
Authors: Mansour Jamal K. , Hamilton Claire M. , Gibson Matthew T.
Published: December 2018

We examined the role of exposure duration and scene complexity on the weapon focus effect (WFE). Memory for the mock crime was affected more by a weapon than an unusual but nonthreatening object. Threat reduced correct identifications when the event was short but not long; duration of the event did not interact with unusualness. Additionally, we found a WFE for target‐absent lineup decisions, but only for the accomplice lineup, not the object‐wielding perpetrator's lineup. We discuss the implications of these results for illuminating the mechanisms that elicit the WFE.
Buprenorphine better than Vivitrol in cost‐effectiveness study
Authors: Knopf Alison
Published: December 2018

For patients who are not already opioid‐free, buprenorphine‐naloxone is preferable to extended‐release naltrexone (Vivitrol), when both options are clinically appropriate, a new study has found. The main reason is the requirement that patients first be withdrawn from all opioids for a week before starting Vivitrol. The study, “Cost‐Effectiveness of Buprenorphine–Naloxone Versus Extended‐Release Naltrexone to Prevent Opioid Relapse,” is by Sean M. Murphy, Ph.D., and colleagues and was published in the Dec. 18 issue of the Annals of Internal Medicine.
Never too late: Older‐adult treatment for alcohol issues carries many benefits
Authors: Enos Gary
Published: December 2018

Treatment for an alcohol use disorder in an older adult likely won't reverse every health effect resulting from a near‐lifetime of drinking, but treatment and research leaders interviewed by ADAW resoundingly agree that addressing alcohol use problems in the older population will prove to merit the effort.
MTF: Dramatic increase in teen vaping of nicotine
Authors: Knopf Alison
Published: December 2018

It shouldn't be a surprise that more teens are vaping, but the increase from last year to this year was dramatic, according to results from the 2018 Monitoring the Future (MTF) survey announced by the National Institute on Drug Abuse (NIDA) last week. In 2017, 27.8 percent of 12th graders reported vaping in the past year; in 2018, this was up to 37.3 percent. In addition, it's clear that more teens are vaping nicotine, not flavors. Last year, teens may not have been sure what they were getting (see ADAW, Dec. 18, 2017).
42 CFR Part 2 at risk during last days of lame‐duck session
Authors: Knopf Alison
Published: December 2018

This week, while most people are on some kind of vacation, there could still be action taken in Congress to decimate 42 CFR Part 2, the regulation requiring treatment providers to obtain consent from substance use disorder (SUD) patients before releasing their records. For almost the past 10 years, this regulation has been under fire, because it makes things inconvenient for electronic health records (EHRs). And until last fall, the organizations that wanted to kill the regulation were bigger and stronger on a regular basis. But when Congress was on the verge of passing its bill that would have gutted the regulation, which is promulgated (and now opposed) by the Substance Abuse and Mental Health Services Administration (SAMHSA), a big fish waded into the pond: the American Medical Association (AMA). Saying what treatment providers like the American Association for the Treatment of Opioid Dependence have been saying for years, the AMA said in a letter to Congress that the regulation, in protecting patients, encouraged them to seek treatment, and that without that guarantee of confidentiality, patients might not want treatment.
A head start for life history development? Family income mediates associations between height and immune response in men
Authors: Krams Indrikis , Luoto Severi , Rubika Anna , Krama Tatjana , Elferts Didzis , Krams Ronalds , Kecko Sanita , Skrinda Ilona , Moore Fhionna R. , Rantala Markus J.
Published: December 2018

Objectives

Male height and health affect a diverse range of social and economic outcomes such as competition for resources and mates. Life history theory predicts that limited availability of bioenergetic resources curbs the development of central life history functions such as somatic growth, immunity, and investment in offspring. Although genetic factors are important determinants of height, other factors such as income level may affect the incidence of infections during ontogeny, thus having indirect effects on somatic growth. We tested whether growing up in families with a higher income positively affects height and immune function.

Materials and Methods

Seventy‐three young Latvian men from various socioeconomic backgrounds were given a hepatitis B vaccine. Blood samples were subsequently collected to measure the antibodies produced in response to the vaccination. Tweedie compound Poisson generalized linear models were used to examine relationships between height, family income, and antibody titers.

Results

Both height and family income positively correlated with the strength of men's immune response. However, when testing for the simultaneous effects of height and income on antibody titers, the statistical models showed that height affected antibody levels indirectly because income level mediated variance in height.

Discussion

The results of this study show that the relationships between height and immune function in young men are more complex than previously thought. Associations between taller stature of men and the robustness of their immune response are indirect because resource availability affects both somatic growth and the development of the immune system.
A comparative study on the effect of different reactive compatibilizers on injection‐molded pieces of bio‐based high‐density polyethylene/polylactide blends
Authors: Quiles‐Carrillo L. , Montanes N. , Jorda‐Vilaplana A. , Balart R. , Torres‐Giner S.
Published: December 2018

The present study reports on the development of binary blends consisting of bio‐based high‐density polyethylene (bio‐HDPE) with polylactide (PLA), in the 5–20 wt % range, prepared by melt compounding and then shaped into pieces by injection molding. In order to enhance the miscibility between the green polyolefin and the biopolyester, different reactive compatibilizers were added during the melt‐blending process, namely polyethylene‐grafted maleic anhydride (PE‐g‐MA), poly(ethylene‐co‐glycidyl methacrylate) (PE‐co‐GMA), maleinized linseed oil (MLO), and a combination of MLO with dicumyl peroxide (DCP). Among the tested compatibilizers, the dual addition of MLO and DCP provided the binary blend pieces with the most balanced mechanical performance in terms of rigidity and impact strength as well as the highest thermal stability. The fracture surface of the binary blend piece processed with MLO and DCP revealed the formation of a continuous structure in which the dispersed PLA phase was nearly no discerned in the bio‐HDPE matrix. The resultant miscibility improvement was ascribed to both the high solubility and plasticizing effect of MLO on the PLA phase as well as the crosslinking effect of DCP on both biopolymers. The latter effect was particularly related to the formation of macroradicals of each biopolymer that, thereafter, led to thein situformation of bio‐HDPE‐co‐PLA copolymers and also to the development of a partially crosslinked network in the binary blend. As a result, cost‐effective and fully bio‐based polymer pieces with improved mechanical strength, high toughness, and enhanced thermal resistance were obtained. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47396.
The State of Cardiovascular Developmental Biology is Strong — Honoring Dr. Roger Markwald and his Seminal Contributions to the Field
Authors: Wessels Andy
Published: December 2018

In August 2017, the Cardiovascular Developmental Biology Center (CDBC), together with the “Department of Regenerative Medicine and Cell Biology (RMCB) at the Medical University of South Carolina (MUSC), organized their 13th Annual CDBC Symposium. During this special event, which was organized in collaboration with The Anatomical Record, the unique and important contributions of Dr. Roger Markwald (known to all of us as Roger) to the field of cardiovascular research were celebrated. Fifteen leading investigators in the field presented their ideas and reported results of their studies to an audience that included many familiar faces from Roger's past and present. This group consisted of established investigators from around the world as well as young and upcoming scientists from local institutions. In their presentations, the platform speakers emphasized the significance of Roger's scientific contributions and advice to their professional development and career. In this Special Issue of The Anatomical Record, we assembled a collection of invited papers written by several attendees of the symposium. The issue also contains a number of articles written by colleagues who, for one reason or the other, were not able to attend the meeting, but expressed their desire to contribute to this special “festschrift” of The Anatomical Record in honor and recognition of Roger's amazing career. Anat Rec, 302:14–18, 2019. © 2018 Wiley Periodicals, Inc.
Isolation and screening for limonin‐producing endophytic bacteria from Citrus maxima (Burm.) Merr. cv. Shatian Yu
Authors: Zhang Jinhua , Zang Sanli , Bai Baoqing , Fan Sanhong
Published: December 2018

Limonin, a compound of highly oxidized triterpenoids, has potential functions in preventing or slowing the occurrences of many diseases. In this study, five different bacterial strains were isolated and identified from Citrus maxima (Burm.) Merr. cv. Shatian Yu. Morphological characteristics and 16S rRNA gene sequencing identified them as Bacillus spp, in which two limonin‐producing endophytes named P and P9 were discovered by high‐performance liquid chromatography and mass spectrometry using an inorganic salt medium and two natural media; also the production was greater in natural medium 1 (4.377 and 0.299 mg/L, respectively) than in natural medium 2 (0.159 and 0.025 mg/L, respectively). The growth and fermentation characteristics of strain P were studied, and during the liquid cultivation of Bacillus sp. P, limonin began to accumulate at the eighth hour in the inorganic salt medium, peaked at the 16th hour, and then decreased sharply. Single‐factor experiments revealed that the optimum fermentation conditions for limonin production included 14‐H‐old cells, 15% inoculum, and 3 g/L glucose.
Solution effects on the self‐association of a water‐soluble peptoid
Authors: Fuller Amelia A. , Huber Jonathan , Jimenez Christian J. , Dowell Kalli M. , Hough Samuel , Ortega Alberto , McComas Kyra N. , Kunkel Jeffrey , Asuri Prashanth
Published: December 2018

A desire to replicate the structural and functional complexity of proteins with structured, sequence‐specific oligomers motivates study of the structural features of water‐soluble peptoids (N‐substituted glycine oligomers). Understanding the molecular‐level details of peptoid self‐assembly in water is essential to advance peptoids' application as novel materials. Peptoid 1, an amphiphilic, putatively helical peptoid previously studied in our laboratory, shows evidence of self‐association in aqueous solution. In this work, we evaluate how changes to aqueous solution conditions influence the self‐association of 1. We report that changes to pH influence the fluorescence and CD spectroscopic features as well as the peptoid's interaction with a solvatochromic fluorophore and its apparent size as estimated by size exclusion chromatography. Addition of guanidine hydrochloride and ammonium sulfate also modulate spectroscopic features of the peptoid, its interaction with a solvatochromic fluorophore, and its elution in size exclusion chromatography. These data suggest that the ordering of the self‐assembly changes in response to pH and with solvent additives and is more ordered at higher pH and in the presence of guanidine hydrochloride. The deeper understanding of the self‐association of 1 afforded by these studies informs the design of new stimuli‐responsive peptoids with stable tertiary or quaternary structures.
Extension of the yeast metabolic model to include iron metabolism and its use to estimate global levels of iron‐recruiting enzyme abundance from cofactor requirements
Authors: Dikicioglu Duygu , Oliver Stephen G.
Published: December 2018

Metabolic networks adapt to changes in their environment by modulating the activity of their enzymes and transporters; often by changing their abundance. Understanding such quantitative changes can shed light onto how metabolic adaptation works, or how it can fail and lead to a metabolically dysfunctional state. We propose a strategy to quantify metabolic protein requirements for cofactor‐utilising enzymes and transporters through constraint‐based modelling. The first eukaryotic genome‐scale metabolic model to comprehensively represent iron metabolism was constructed, extending the most recent community model of the Saccharomyces cerevisiae metabolic network. Partial functional impairment of the genes involved in the maturation of iron‐sulphur (Fe‐S) proteins was investigated employing the model and the in silico analysis revealed extensive rewiring of the fluxes in response to this functional impairment, despite its marginal phenotypic effect. The optimal turnover rate of enzymes bearing ion cofactors can be determined via this novel approach; yeast metabolism, at steady state, was determined to employ a constant turnover of its iron‐recruiting enzyme at a rate of 3.02 × 10
−11 mmol·(g biomass)
−1·h 
−1.
Guided inquiry activity linking thermodynamic parameters of protein unfolding to structure using differential scanning fluorimetry data in the biophysical chemistry classroom
Authors: Emery Patrick , Yezierski Ellen J. , Page Richard C.
Published: December 2018

Visualizations are useful tools for helping students to understand chemistry concepts at the particulate level. A classroom activity was developed based on learning theory and evidence‐based practices, combining protein visualization with thermodynamic parameters from differential scanning fluorimetry (DSF) data analysis. Coding of student responses showed that many students were able to establish the desired connections among protein structure, thermodynamic parameters, and experimental data analysis, while a few did not recognize all the differences between the folded and unfolded forms of the protein. The activity elicits student prior knowledge through the pre‐class activity, has the students examine the interactions within a protein molecule through the PyMOL activity, introduces DSF analysis using the learning cycle through the Guided Inquiry activity, and tests student learning through the post‐class activity. Upon completing the activity, the majority of students successfully met the learning goals. © 2018 International Union of Biochemistry and Molecular Biology, 47(1):67–75, 2018.
Computational strategy for visualizing structures and teaching biochemistry
Authors: Abreu Paula Alvarez , Carvalho Karina de Lima , Rabelo Vitor Won‐Held , Castro Helena Carla
Published: December 2018

Computational techniques have great potential to improve the teaching‐learning. In this work, we used a computational strategy to visualize three‐dimensional (3D) structures of proteins and DNA and help the student to comprehend biochemistry concepts such as protein structure and function, substrate, and inhibitors as well as DNA structural features. The practical classes included tutorials to be done in the computer using structures from Protein Data Bank and a free 3D structure visualization software, Swiss PDB Viewer. The activity was done with 76 students from biology and pharmacy undergraduate courses. Questionnaires were administered to evaluate the knowledge regarding specific biochemistry contents before and after the activity and the opinion of the students. An overall increased percentage of correct answers post‐classes (75.91%) were observed in comparison to pre‐classes (35.53%). All the students indicated that it could contribute to the learning of DNA and protein structure contents; approximately 90% stated that it enables structures visualization or makes the learning and understanding easier. Therefore, the strategy has shown to be effective, allowing the contextualization of biochemistry themes and may complement theoretical classes. © 2018 International Union of Biochemistry and Molecular Biology, 47(1):76–84, 2018.
Application of mass spectrometry in silkworm research—Review
Authors: Sun Fan , Ye Chong Jun , Li Bing , Wang Taichu , Fan Tao
Published: December 2018

In this first mass spectrometry‐focused review paper, we will review current applications of mass spectrometry in the area of silkworm research. We will focus our review on the following two most important areas as they are currently being researched by scientists. Firstly, the proteomics of proteins in the process of silkworm lifecycle has generated knowledge about previous undetected proteins, some of which might possess therapeutic effects. Secondly, fatty acids, which are the other major components in silkworm, have several potential medical applications. We will also highlight potential areas warranting further investigation.
Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae
Authors: He Yaqiong , Zhang Wancun , Peng Fan , Lu Ruili , Zhou Hong , Bao Guanhu , Wang Bin , Huang Bo , Li Zengzhi , Hu Fenglin
Published: December 2018

Isaria cicadae is one of the fungi used in traditional Chinese medicine with the longest tradition. It is used not only as a herbal medicine but also as a health food in Asia, together with cultured cordyceps and mycelia of the fungus used as substitute. However, the differences in their metabolite are unknown. Using a high‐performance liquid chromatography–mass spectrometry (HPLC–MS)‐based metabolomic method, we found that the fungus varies in its metabolism during growth on wild insects, artificially raised insects and artificial medium. There were 109 discriminatory metabolites detected in the samples by orthogonal projection to latent structure discriminant analysis and one‐way ANOVA. High level of nonribosomal peptides (NRPs) only existed in the insect portions of the wild cordyceps (WI) and cultured cordyceps (CI), revealing that immunostimulation of the host insects enhanced the synthesis of NRPs in the fungus. The finding of a significantly higher level of sphingolipids in both the insect portions (WI, CI) and the coremia of the wild cordyceps (WC) and cultured cordyceps (CC) but not in cultured mycelia (CM) of I. cicadae implies that the immunostimulation of the live insects can induce the fungus to produce more sphingolipids, and this enhanced ability is probably heritable. Apart from NRPs and sphingolipids, the insect portions also contained higher levels of bioactive compounds such as lateritin, anisomycin, streptimidone and ustiloxins. In contrast, the coremium groups (WC, CC) and CM contained 10‐fold less NRP but much higher levels of sanative metabolites such as tocotrienol, 3′‐deoxy‐hanasanagin, γ‐aminobutyric acid and phospholipids than the insect portions. The significantly higher content of antioxidants in WC, CC and CM than in WI and CI suggests that environmental oxygen has a significant effect on the metabolites. The temperature stress which the wild cordyceps encounters during growth is responsible for the relatively high content of trehalose. These findings indicate that the immunity of the host insect and growth environment have a strong impact on the metabolomic variation in Isaria cicadae. The variation in metabolites suggests differential utilization value for the insect portions, coremia and mycelia of the fungus.
Positron emission tomography/computed tomography outperforms MRI in the diagnosis of local recurrence and residue of nasopharyngeal carcinoma: An update evidence from 44 studies
Authors: Li Zhanzhan , Li Yanyan , Li Na , Shen Liangfang
Published: December 2018

Studies on nasopharyngeal carcinoma (NPC) in five electronic databases were systematically searched online from the inception to June 5, 2018. Quality of the included studies was assessed using the updated Quality Assessment of Diagnostic Accuracy Studies 2. Data of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the 95% confidence intervals were pooled using a bivariate random‐effect model. Forty‐four studies with 61 groups of data and totally 3369 patients were included in the qualitative and quantitative synthesis analysis. The overall estimated sensitivity and specificity of positron emission tomography/computed tomography/magnetic resonance imaging (PET‐CT/MRI) for local recurrent/residual NPC were 0.90 and 0.85, respectively. The pooled area under the curve of (AUC) of PET‐CT/MRI in the summary receiver operator characteristic curve was 0.94. Subgroup analysis showed MRI vs PET‐CT had lower sensitivity (0.83 vs 0.92) and specificity (0.78 vs 0.89). The AUCs of MRI and PET‐CT were 0.87 and 0.96, respectively. No‐cross of 95% CI was found in MRI vs PET/CT (0.87‐0.90 vs 0.94‐0.98). Meta‐regression showed PET/CT vs MRI was a potential source of heterogeneity. PET/CT and MRI both showed quite high overall ability in diagnosing local recurrent/residual NPC, but the subgroup analysis indicated PET‐CT was superior over MRI in diagnosis of local recurrence and residue of NPC after radiotherapy. The examination methods affected the heterogeneity within studies.
Surgical Treatment of a Cemental Tear‐Associated Bony Defect Using Hyaluronic Acid and a Resorbable Collagen Membrane: A 2‐Year Follow‐Up
Authors: Pilloni Andrea , Nardo Flavia , Rojas Mariana A.
Published: December 2018

Introduction

A cemental tear (CeT) is a special type of surface root fracture that may cause periodontal and even periapical tissue destruction.

Unfortunately, there is limited knowledge as to how these rare cases can effectively be treated. The present case is believed to be the first reported in the literature treating a bony defect caused by a cemental tear with hyaluronic acid (HA) and a collagen membrane. The aim of this case report is to present a regenerative surgical approach with clinical and tomographic success and stability at 2‐year follow‐up.

Case Presentation

A 61‐year‐old patient presented with spontaneous pain and gingival swelling over his right central maxillary incisor. Radiographically, a radiolucent area was observed in the medial third between both central incisors. The tomographic evaluation showed a buccal bone dehiscence and a bony defect. Once the differential diagnosis with an endodontic‐periodontal lesion and root fracture was performed, CeT was the presumptive diagnosis. During the exploratory flap surgery, a small root fragment (CeT) on the mesial side of the tooth was founded and removed. The bony lesion was treated with hyaluronic acid (HA) and a resorbable collagen membrane. At 2‐year follow‐up clinical, radiographic, and tomographic success was observed.

Conclusion

A CeT‐associated bony defect could be successfully treated after removing cemental fragments and performing a regenerative approach using HA and a resorbable collagen membrane.
Gluten viscoelasticity: Rapid method for classification of soft‐like wheat genotypes
Authors: Montagner Souza Thiago , de Miranda Martha Zavariz , Mateus Prando Andre , Tilley Michael , Payton Mark E. , Rayas‐Duarte Patricia
Published: December 2018

Background and objectives

Standard empirical methods to assess wheat quality are difficult to perform, interpret, time consuming and require a large amount of sample. A rapid uniaxial compression instrument based on measuring height of gluten during compression and recovery is reported. The objective of this study was to determine in a set of soft‐like wheat genotypes from Brazil the best conditions to extract the gluten and analyze the efficiency of the method separating categories based on gluten viscoelastic properties.

Findings

The independent variables evaluated were as follows: (a) technological quality categories and gluten extraction method; (b) amount of 2% NaCl solution (w/v) added for dough formation; (c) mixing time; and (d) washing time. The results were submitted to analysis of variance and means compared by protected LSD test (p < 0.05). The best conditions for gluten extraction and analysis were obtained with 4.4 ml of 2% NaCl solution, mixing for 20 s, and washing for 3 min. Elastic recovery of gluten showed a strong correlation (r) with standard methods used to classify wheat (dough strength r = 0.988, stability r = 0.963).

Conclusion

The elastic recovery was able to separate the gluten samples in three categories efficiently and may be a useful tool in breeding programs and flour mills quality control.

Significance and novelty

A novel method for determining elastic recovery of gluten from soft‐type wheat genotypes was developed. The set of samples had high correlation of gluten elastic recovery with key quality parameters. Advantages of the test include rapid analysis time (less than 5 min) and small sample size (10 g of flour).
Clinical scores used for the prediction of negative events in patients undergoing catheter ablation for atrial fibrillation
Authors: Kosich Falco , Schumacher Katja , Potpara Tatjana , Lip Gregory Y. , Hindricks Gerhard , Kornej Jelena
Published: December 2018

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults. Catheter ablation (CA) is one of the most important management strategies to reduce AF burden and AF‐associated complications. In order to stratify the risk of adverse events and to predict treatment success in AF patients undergoing CA, several risk stratification scores had been developed during the last decade. The aim of this review is to provide an overview of the most important clinical risk scores predicting rhythm outcomes, electro‐anatomical substrate and mortality in AF.
Ejection fraction, B‐type natriuretic peptide and risk of stroke and acute myocardial infarction among patients with heart failure
Authors: Greenberg Barry , Peterson Eric D. , Berger Jeffrey S. , Laliberté François , Zhao Qi , Germain Guillaume , Lejeune Dominique , Wu Jennifer W. , Lefebvre Patrick , Fonarow Gregg C.
Published: December 2018

Background

Real‐world data on the clinical outcomes of heart failure (HF) across the spectrum of ejection fraction (EF) and the prognostic value of B‐type natriuretic peptide (BNP) have not been well examined.

Hypothesis

The real‐world association between the clinical outcomes of HF and EF or BNP levels may differ across different EF or BNP values.

Methods

The Optum Integrated Claims‐Clinical data (07/2009‐09/2016) was used to identify adult patients with ≥1 HF diagnosis during hospitalization or emergency room visit. Three EF cohorts were formed: reduced (rEF; EF < 40%), mid‐range (mrEF; EF 40%‐49%), and preserved EF (pEF; EF ≥ 50%). Stratifications by BNP levels were performed using median BNP as cutoff between high vs low BNP (H‐BNP vs L‐BNP).

Results

In total, 7005 HF patients with EF measurements (2456 patients with both HF and BNP measurements) were identified. rEF patients had higher risk of stroke (hazard ratio [HR] = 1.57, P = 0.010) and acute myocardial infarction (AMI) (HR = 2.42, P < 0.001) compared to pEF patients. H‐BNP was associated with a significantly higher risk of mortality (P < 0.001). rEF patients with H‐BNP had a significantly higher risk of stroke than those with L‐BNP.

Conclusions

Patients with rEF had a significantly higher rate of stroke and AMI vs pEF patients, as did patients with H‐BNP vs L‐BNP. The present study is the first to show the real‐world association of EF and BNP (alone and in combination) with clinical outcomes, further supporting the recommendation to use these markers in clinical practice. These results may help to guide future recommendations and improve the clinical management of HF.
Two‐Color Analysis of Leukocytes Labeled by Modified RBCs and Their Fragments
Authors: Al‐Essa Mohamed K. , Melzer Susanne , Tárnok Attila
Published: December 2018

Red blood cells (RBCs) are attractive tools for surface modification to adhere specifically to molecules, cellular fragments (e.g., microvesicles), or whole cells for potential use in bioanalytical assays or as a delivery vehicle in targeted therapy. Within this study, we have loaded RBCs with fluorochrome‐conjugated antibodies (Ab) against CD45 and CD22 leukocyte markers and evaluated the conjugation process by microscopy. We have assessed the potential application of RBCs fragments generated from conjugated RBCs for targeting Cyto‐Trol control cells by flow cytometric (FCM) approaches. Based on their scattering and fluorescence characteristics (FITC and PE expression), modified RBCs and their fragments, Cyto‐Trol cells, and clusters of both were distinguished by two color FCM analysis. Fragments with anti‐human Kallestad Ab as a nonspecific FITC conjugate had less than 20% binding to Cyto‐Trol controls compared to CD45‐FITC Ab conjugate with nearly 100% binding capacity. Cyto‐Trol‐microvesicle‐clusters were more than 45% positive for either FITC or PE. Anti‐CD22‐PE modified RBCs fragments were also useful in staining and showing about 19.5% positively stained events in the Cyto‐Trol region. The proof‐of‐concept shows, that specific antibody can be attached to RBCs, and generated fragments can be useful to stain target cells for FCM analysis. © 2018 International Society for Advancement of Cytometry
Jejunal leiomyosarcoma: Report of a rare case diagnosed on cytology
Authors: Elhence Poonam Abhay , Rao Meenakshi , Vishnoi Jeewan Ram , Meena Virendra
Published: December 2018

Jejunal leiomyosarcomas (LMS) are extremely rare. Of all the mesenchymal tumors of the small intestine, Gastrointestinal Stromal Tumors (GIST) comprise the majority. LMS of the small intestine have been documented as isolated reports or only a very small percentage of the smooth muscle tumors of the small intestine. Furthermore, cytological evaluation and preoperative diagnosis of small intestinal LMS is not well documented, even though cytology of small intestinal GISTs has been studied. Since preoperative diagnosis is useful in differentiating benign from malignant lesions, correctly staging malignant lesions and identifying the plan of management, preoperative cytological evaluation assumes a great significance. We report a case of jejunal leiomyosarcoma diagnosed on cytology.

Key Messages

Although extremely rare, small intestinal LMS should be considered in the differential diagnosis of small intestinal mesenchymal lesions. FNAC, with preparation of cell block, and subsequent IHC can help in the preoperative diagnosis and formulating a plan of management of the patients.
Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising flunitrazolam, norflurazepam, and 4'‐chlorodiazepam (Ro5–4864)
Authors: Moosmann Bjoern , Bisel Philippe , Westphal Folker , Wilde Maurice , Kempf Jürgen , Angerer Verena , Auwärter Volker
Published: December 2018

The number of newly appearing benzodiazepine derivatives on the new psychoactive substances (NPS) drug market has increased over the last couple of years totaling 23 ‘designer benzodiazepines’ monitored at the end of 2017 by the European Monitoring Centre for Drugs and Drug Addiction. In the present study, three benzodiazepines [flunitrazolam, norflurazepam, and 4′‐chlorodiazepam (Ro5–4864)] offered as ‘research chemicals' on the Internet were characterized and their main in vitro phase I metabolites tentatively identified after incubation with pooled human liver microsomes. For all compounds, the structural formula declared by the vendor was confirmed by gas chromatography−mass spectrometry (GC–MS), liquid chromatography−tandem mass spectrometry (LC MS/MS), liquid chromatography−quadrupole time of flight−mass spectrometry (LC−QTOF−MS) analysis and nuclear magnetic resonance (NMR) spectroscopy. The metabolic steps of flunitrazolam were monohydroxylation, dihydroxylation, and reduction of the nitro function. The detected in vitro phase I metabolites of norflurazepam were hydroxynorflurazepam and dihydroxynorflurazepam. 4’‐Chlorodiazepam biotransformation consisted of N‐dealkylation and hydroxylation. It has to be noted that 4′‐chlorodiazepam and its metabolites show almost identical LC–MS/MS fragmentation patterns to diclazepam and its metabolites (delorazepam, lormetazepam, and lorazepam), making a sufficient chromatographic separation inevitable. Sale of norflurazepam, the metabolite of the prescribed benzodiazepines flurazepam and fludiazepam, presents the risk of incorrect interpretation of analytical findings.