bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing incidence of IV‐drug use associated endocarditis in southern West Virginia and potential economic impact
Authors: Bates Mark C. , Annie Frank , Jha Ayan , Kerns Fred
Published: February 2019

Background

The opioid crisis has disproportionally affected Appalachia. One of the potentially lethal and costly complications associated with IV drug use is infective endocarditis (IE). The goal of this study was to assess the trend and costs of substance abuse associated IE admissions in Southern West Virginia.

Methods

This is a retrospective analysis of cost, incidence, and geographic patterns of all patients admitted over the last decade with concomitant drug abuse (cocaine, amphetamine, sedative, and other/mixed drug abuse) and IE in the largest tertiary care center for Southern West Virginia. A time series model was used to investigate the effect of drug use on the incidence of IE.

Results

A total of 462 patients were hospitalized with IE and concomitant illicit drug use. IE cases increased from 26 admissions in 2008 to 66 in 2015. Patterns of increases in mixed drug use (DRG most often associated with IV drug use in our center) mirrored increases in IE (P = 0.001). From 2008 to 2015, the total hospital charges were $17 306 464 on 462 cases of illicit drug associated IE. Only a fraction of the billed fees (22%) was collected ($3 829 701).

Conclusions

The number of patients hospitalized with IE has dramatically increased over the last decade in a pattern that mirrors the increase in mixed drug use. The majority of payers were from underfunded state programs or private pay and thus, only 22% of the hospital charges were paid, leaving a hospital deficit of over $13 476 763 during the study period.
Response of Soil Nematode Community to Phosphorous Amendment in a Subalpine Spruce Plantation
Authors: Yang Bing , Zhang Tao , Huang Junsheng , Bhusal Daya Ram , Pang Xueyong
Published: February 2019

An appropriate management practice is indispensable to the restoration of ecological functioning, particularly in ecologically vulnerable regions. The short‐term effects of phosphorous (P) amendment on community structure and function of soil micro‐food webs in a subalpine spruce (Picea asperata) plantation are examined. Experimental plots are established and treatments are performed with P addition at two levels: Low P (LP) input of 5 g m−2per year and high P (HP) input 30 g m−2per year as NaH2PO4 · 2 H2O, and in control plots (CK) without external P input. The abundance, diversity, functional indices, community composition, and metabolic footprints of soil nematodes in the experimental plots are monitored for two consecutive growing seasons during 2013–2014 following P addition. A high variation of abundance of nematodes is observed especially in HP treatment, with reduction in abundance of omnivores and predators. Similarly, maturity index of free‐living nematodes, plant parasitic index, enrichment index, structure index, and predator footprint are significantly reduced. However, basal index and channel index of soil nematodes are apparently increased in both years. Moreover, P addition considerably shifts soil nematode community composition, which correlates to soil pH, total P content, available P content, and molar C/P and N/P in soils. In summary, the results indicate that the impacts of P addition on soil nematode community in spruce plantation are mediated by changes in soil pH, P status, and C/N/P ecological stoichiometry.
Dissipative ion‐acoustic waves in collisional electron‐positron‐ion plasmas with Kappa distribution
Authors: Mehdipoor M.
Published: February 2019

In this work, linear and non‐linear structures of ion‐acoustic waves (IAWs) are investigated in a collisional plasma consisting of warm ions, superthermal electrons, and positrons. A dissipative effect is assumed due to ion‐neutral collisions. The linear properties of IAWs are investigated. It is shown that the dynamics of the IAWs is governed by the damped Korteweg‐de Vries (K‐dV) equation. It is seen that the ion‐neutral collisions modify the basic features of ion‐acoustic solitary waves significantly. Also, the effect of the plasma parameters on the dissipative IAWs is discussed in detail.
Secure user authentication scheme with novel server mutual verification for multiserver environments
Authors: Park YoHan , Park KiSung , Park YoungHo
Published: February 2019

The fast growth of mobile services and devices has made the conventional single‐server architecture ineffective from the point of its functional requirements. To extend the scalability and availability of mobile services to various applications, it is required to deploy multiserver architecture. In 2016, Moon et al insisted that Lu et al's scheme is weak to insiders and impersonation attack, then they proposed a biometric‐based scheme for authentication and key agreement of users in multiserver environments. Unfortunately, we analyze Moon et al's scheme and demonstrate that their scheme does not withstand various attacks from a malicious registered server. We propose a user authentication scheme with server mutual verification to overcome these security drawbacks. The proposed scheme withstands an attack from malicious insiders in multiserver environments. We use a threshold cryptography to strengthen the process of server authorization and to provide better security functionalities. We then prove the authentication and session key of the proposed scheme using Burrows‐Abadi‐Needham (BAN) logic and show that our proposed scheme is secure against various attacks.
A BUS‐aided RSU access scheme based on SDN and evolutionary game in the Internet of Vehicle
Authors: Jia Fang , Chen Chen , Li Jiajun , Chen Lanlan , Li Na
Published: February 2019

The Internet of Vehicle (IoV) is known as a kind of highly dynamic network, in which the vehicle needs to exchange information with the fixed Roadside Unit (RSU) or other moving vehicles frequently. In order to improve the performance of existing RSU access schemes, in this paper, we proposed a BUS‐aided RSU connection scheme based on the software‐defined networking (SDN) and evolutionary game theory, in which the costs during multiple‐user access and following RSU handoff are considered. At first, we constructed a SDN‐IoV architecture and showed the benefits by introducing SDN into IoV. After that, we modified the original OpenFlow protocol stack in order to apply it to the wireless vehicular networks. Next, to explore more accessing opportunities in moving cases, the BUS was further introduced as a mobile RSU. With these fixed and mobile RSUs, an evolutionary game is then envisioned to model the multiple‐user access process with the aim to maximize the rewards of all participants. To make our proposed protocol practical, we also illustrated the implementation procedure of our protocol on the OPNET platform and gave out the finite state machine (FSM) of major routines. Numerical results showed that our proposed scheme could outperform the schemes without BUS, SDN, and game theory enabled, in terms of RSU load ratio, throughput, and handoff times.
Give students ownership of credentials with blockchain technology
Authors: Hope Joan
Published: February 2019

When the enrollment services division at Central New Mexico Community College started looking at digital services for diplomas, transcripts, and other credentials, they were guided by the institution's strategic plan. One of the plan's priorities was to shift from college‐owned technology to student‐owned technology, said Feng Hou, chief information officer and chief digital learning officer.
Think big, collaborate for a successful deanship
Authors: Hope Joan
Published: February 2019

Next academic year, Jennifer Wolch's life will be quite different. After 10 years as William W. Wurster Dean of the College of Environmental Design at the University of California, Berkeley, Wolch is stepping down this summer, with a sabbatical planned. Reflecting on her years as dean, accomplishments Wolch is most proud of include.
Undoing ableism in the institution
Authors: LoGiudice Joseph A.
Published: February 2019

Colleges and universities strive to ensure their students who possess various identities, especially those of minority status, experience an inclusive, diverse, and integrated setting where a plurality of views are welcomed and exchanged among individuals. However, postsecondary institutions are unable to undo historical power, privilege, and oppression that has been built (literally) into the infrastructure, policies, and practices.
Create a comprehensive program to support students with ASD
Authors: Hope Joan
Published: February 2019

Lynn Gallagher, Ed.D., CAS, director of the Lynch Learning Center at Loras College in Iowa, explained how the college supports students with autism spectrum disorder through the ARCH program.
Disability education through campus programming
Authors: Bohler Stephanie Russo
Published: February 2019

As disability services professionals, we often take for granted our knowledge of the field and expect that everyone at our institution has the same level of understanding. This can lead to frustration as we encounter people on campus who seem to lack empathy due to discomfort with involvement in accommodations or who show reservation in discussing disability. Their reactions are likely a result of avoiding what they have been taught is a sensitive topic that is rude to discuss.
Association of oxidative stress and inflammatory markers with chronic stress in patients with newly diagnosed type 2 diabetes
Authors: Siddiqui Azaz , Desai Nimesh G. , Sharma Suman B. , Aslam Mohammad , Sinha Uday K. , Madhu Sri V.
Published: February 2019

Aims

Chronic stress is associated with increased risk of type 2 diabetes. Oxidative stress and inflammation are potential mediators of this risk. This study was conducted to investigate the association of oxidative stress and inflammatory markers with chronic stress and newly diagnosed type 2 diabetes.

Methods

Oxidative stress/antioxidant status (malondialdehyde [MDA], reduce glutathione [GSH], glutathione reductase [GR], glutathione peroxidase [GPx], catalase [CAT], superoxide dismutase [SOD]), inflammatory markers (highly sensitive C‐reactive protein [hsCRP], adiponectin, leptin), chronic stress levels as assessed by stress scales—presumptive stressful life events scale (PSLES), perceived stress scale (PSS), sense of coherence (SOC) and stress biomarker—salivary cortisol in 125 subjects with newly detected diabetes mellitus (NDDM) were compared with an equal number of age and sex matched subjects with normal glucose tolerance (NGT).

Results

NDDM subjects as compared with NGT had significantly increased MDA (P < 0.001), hsCRP (P < 0.001), and leptin (P = 0.014) levels and increased GR (P = 0.043) and SOD (P < 0.001) activity along with decreased GSH (P < 0.001) and adiponectin (P < 0.001) levels. They also had significantly higher PSLES‐LT and PSS and lower SOC scores along with elevated levels of 10:00 pm salivary cortisol and post dexamethasone salivary cortisol as compared with NGT. In stepwise logistic regression analysis, variables GSH (OR: 0.805), SOD (OR: 1.004), and adiponectin (OR: 0.771) along with PSLES‐LT (OR: 1.007), PSS (OR: 1.147), SOC (OR: 0.667), salivary cortisol 10:00 pm (OR: 1.382), WC (OR: 1.087), and HOMA‐IR (OR: 2.721) emerged as significant predictors of NDDM.

Conclusion

The findings of this study indicate that chronic psychological stress and stress responses are associated significantly with inflammation and oxidative stress, which could act as mediating stress related risk factors for type 2 diabetes.
Retinoic acid signaling in vascular development
Authors: Pawlikowski Brad , Wragge Jacob , Siegenthaler Julie A.
Published: February 2019

Formation of the vasculature is an essential developmental process, delivering oxygen and nutrients to support cellular processes needed for tissue growth and maturation. Retinoic acid (RA) and its downstream signaling pathway is vital for normal pre‐ and post‐natal development, playing key roles in the specification and formation of many organs and tissues. Here, we review the role of RA in blood and lymph vascular development, beginning with embryonic yolk sac vasculogenesis and remodeling and discussing RA's organ‐specific roles in angiogenesis and vessel maturation. In particular, we highlight the multi‐faceted role of RA signaling in CNS vascular development and acquisition of blood–brain barrier properties.
A new cognitive behavior therapy for adolescents with avoidant/restrictive food intake disorder in a day treatment setting: A clinical case series
Authors: Dumont Eric , Jansen Anita , Kroes Diana , de Haan Eline , Mulkens Sandra
Published: February 2019

Objective

Avoidant/restrictive food intake disorder (ARFID) is a new diagnosis in the DSM‐5 Feeding and Eating Disorders section, for which very limited treatment research has been carried out, yet. A new, 4‐week exposure based cognitive behavioral therapy (CBT) day treatment, which integrated the inhibitory learning principles, was developed for adolescents with ARFID, and tested in the current study.

Method

A nonconcurrent multiple baseline design was used in a clinical case series of eleven 10‐ to 18‐year‐old patients. After baseline, the 4‐week CBT followed. Measurements of DSM‐5 ARFID diagnosis, food neophobia and related measures such as body weight and length, were taken at baseline (t1), at the end of the 4‐week intensive day treatment (t2) and 3 months after treatment (follow‐up, t3). A food selectivity test, a 1‐week food diary, and behavioral measures on food intake were also taken at baseline and at 3‐month follow‐up. Furthermore, continuous measurements of believability of dysfunctional cognitions, anxiety, and food acceptance were taken throughout the 4‐weeks day treatment.

Results

At follow‐up, 10 out of 11 patients were in remission and had a healthy body weight and an average, age‐adequate nutritional intake. For most patients, food neophobia scores decreased to a nonclinical range. The belief in dysfunctional cognitions and anxiety levels decreased during treatment.

Discussion

This new exposure‐based CBT for adolescents with ARFID seems promising. These results may be very useful for clinical practice and stimulate further development of effective CBT interventions in the area of ARFID.
Molecular diet analysis finds an insectivorous desert bat community dominated by resource sharing despite diverse echolocation and foraging strategies
Authors: Gordon Rowena , Ivens Sally , Ammerman Loren K. , Fenton M. Brock , Littlefair Joanne E. , Ratcliffe John M. , Clare Elizabeth L.
Published: February 2019

Interspecific differences in traits can alter the relative niche use of species within the same environment. Bats provide an excellent model to study niche use because they use a wide variety of behavioral, acoustic, and morphological traits that may lead to multi‐species, functional groups. Predatory bats have been classified by their foraging location (edge, clutter, open space), ability to use aerial hawking or substrate gleaning and echolocation call design and flexibility, all of which may dictate their prey use. For example, high frequency, broadband calls do not travel far but offer high object resolution while high intensity, low frequency calls travel further but provide lower resolution. Because these behaviors can be flexible, four behavioral categories have been proposed: (a) gleaning, (b) behaviorally flexible (gleaning and hawking), (c) clutter‐tolerant hawking, and (d) open space hawking. Many recent studies of diet in bats use molecular tools to identify prey but mainly focus on one or two species in isolation; few studies provide evidence for substantial differences in prey use despite the many behavioral, acoustic, and morphological differences. Here, we analyze the diet of 17 sympatric species in the Chihuahuan desert and test the hypothesis that peak echolocation frequency and behavioral categories are linked to differences in diet. We find no significant correlation between dietary richness and echolocation peak frequency though it spanned close to 100 kHz across species. Our data, however, suggest that bats which use both gleaning and hawking strategies have the broadest diets and are most differentiated from clutter‐tolerant aerial hawking species.
Sex and occupation time influence niche space of a recovering keystone predator
Authors: Rechsteiner Erin U. , Watson Jane C. , Tinker M. Tim , Nichol Linda M. , Morgan Henderson Matthew J. , McMillan Christie J. , DeRoos Mike , Fournier Marie C. , Salomon Anne K. , Honka Leah D. , Darimont Chris T.
Published: February 2019

Predators exert strong effects on ecological communities, particularly when they re‐occupy areas after decades of extirpation. Within species, such effects can vary over time and by sex and cascade across trophic levels. We used a space‐for‐time substitution to make foraging observations of sea otters (Enhydra lutris) across a gradient of reoccupation time (1–30 years), and nonmetric multidimensional scaling (nMDS) analysis to ask whether (a) sea otter niche space varies as a function of occupation time and (b) whether niche space varies by sex. We found that niche space varied among areas of different occupation times. Dietary niches at short occupation times were dominated by urchins (Mesocentrotus and Strongylocentrotus spp; >60% of diets) in open habitats at 10–40 m depths. At longer occupation times, niches were dominated by small clams (Veneroida; >30% diet), mussels (Mytilus spp; >20% diet), and crab (Decapoda; >10% diet) in shallow (<10 m) kelp habitats. Diet diversity was lowest (H′ = 1.46) but energy rich (~37 kcal/min) at the earliest occupied area and highest, but energy poor (H′ = 2.63, ~9 kcal/min) at the longest occupied area. A similar transition occurred through time at a recently occupied area. We found that niche space also differed between sexes, with bachelor males consuming large clams (>60%), and urchins (~25%) from deep waters (>40 m), and females and territorial males consuming smaller, varied prey from shallow waters (<10 m). Bachelor male diets were less diverse (H′ = 2.21) but more energy rich (~27 kcal/min) than territorial males (H′ = 2.54, ~13 kcal/min) and females (H′ = 2.74, ~11 kcal/min). Given recovering predators require adequate food and space, and the ecological interactions they elicit, we emphasize the importance of investigating niche space over the duration of recovery and considering sex‐based differences in these interactions.
Developmental and genetic effects on behavioral and life‐history traits in a field cricket
Authors: Wey Tina W. , Réale Denis , Kelly Clint D.
Published: February 2019

A fundamental goal of evolutionary ecology is to identify the sources underlying trait variation on which selection can act. Phenotypic variation will be determined by both genetic and environmental factors, and adaptive phenotypic plasticity is expected when organisms can adjust their phenotypes to match environmental cues. Much recent research interest has focused on the relative importance of environmental and genetic factors on the expression of behavioral traits, in particular, and how they compare with morphological and life‐history traits. Little research to date examines the effect of development on the expression of heritable variation in behavioral traits, such as boldness and activity. We tested for genotype, environment, and genotype‐by‐environment differences in body mass, development time, boldness, and activity, using developmental density treatments combined with a quantitative genetic design in the sand field cricket (Gryllus firmus). Similar to results from previous work, animals reared at high densities were generally smaller and took longer to mature, and body mass and development time were moderately heritable. In contrast, neither boldness nor activity responded to density treatments, and they were not heritable. The only trait that showed significant genotype‐by‐environment differences was development time. It is possible that adaptive behavioral plasticity is not evident in this species because of the highly variable social environments it naturally experiences. Our results illustrate the importance of validating the assumption that behavioral phenotype reflects genetic patterns and suggest questions about the role of environmental instability in trait variation and heritability.
Epithelium‐specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile
Authors: Mamareli Panagiota , Kruse Friederike , Friedrich Christin , Smit Nathiana , Strowig Till , Sparwasser Tim , Lochner Matthias
Published: February 2019

Infection with Clostridium difficile is one of the major causes of health care acquired diarrhea and colitis. Signaling though MyD88 downstream of TLRs is critical for initiating the early protective host response in mouse models of C. difficile infection (CDI). In the intestine, MyD88 is expressed in various tissues and cell types, such as the intestinal epithelium and mononuclear phagocytes (MNP), including DC or macrophages. Using a genetic gain‐of‐function system, we demonstrate here that restricting functional MyD88 signaling to the intestinal epithelium, but also to MNPs is sufficient to protect mice during acute CDI by upregulation of the intestinal barrier function and recruitment of neutrophils. Nevertheless, we also show that mice depleted for CD11c‐expressing MNPs in the intestine display no major defects in mounting an effective inflammatory response, indicating that the absence of these cells is irrelevant for inducing host protection during acute infection. Together, our results highlight the importance of epithelial‐specific MyD88 signaling and demonstrate that although functional MyD88 signaling in DC and macrophages alone is sufficient to correct the phenotype of MyD88‐deficiency, these cells do not seem to be essential for host protection in MyD88‐sufficient animals during acute infection with C. difficile.
Exploiting the Versatility of Phosphinobenzylsilanes for the Stabilization of 14‐Electron Rhodium(III) and Iridium(III) Complexes
Authors: Corona‐González María Vicky , Zamora‐Moreno Julio , Muñoz‐Hernández Miguel A. , Vendier Laure , Sabo‐Etienne Sylviane , Montiel‐Palma Virginia
Published: February 2019

Incorporating pendant silicon functionalities into phosphine ligands enables to profit from the strong σ‐electron donor and trans influence properties of Si while enhancing the coordination ability of the ligand. Herein, we show that the introduction of bulky sigma donor substituents on the Si atoms and modulation of the number of Si–H functional groups in a series of phosphinobenzylsilanes allow either the stabilization of rare highly unsaturated 14‐electron rhodium(III) and iridium(III) species devoid of agostic interactions or the access to mixed‐valence MI–MIII complexes. Our findings using isopropyl‐substituted silicon are markedly different from those obtained when employing the methyl‐substituted Si series.
Rapid Measuring Flavor Quality Changes of Frying Rapeseed Oils using a Flash Gas Chromatography Electronic Nose
Authors: Xu Lirong , Li Xu , Huang Jianhua , Gao Pan , Jin Qingzhe , Wang Xingguo
Published: February 2019

A flash gas chromatography electronic nose (FGC E‐nose) is applied to measure flavor quality changes and monitor the oxidation process of rapeseed oils during frying. Partial least squares regression (PLS) is applied to determine the relationship between total polar compounds (TPC) and some volatile compounds determined by FGC E‐nose in frying rapeseed oils. Qualitative differentiation between frying oil samples with different frying time is analyzed by principal component analysis (PCA) and hierarchical cluster analysis (HCA). The PCA and HCA results show that the FGC E‐nose could be used to discriminate oil samples with different frying time. The results show a good linear relationship (R2 = 0.98; SD = 1.433) between TPC in oil samples measured by AOCS method and that predicted by the FGC E‐nose responses using PLS method. Thus, this study indicates that the FGC E‐nose method could be available for rapid at‐ or on‐line implementation in oxidation control of frying oils.

Practical Applications: Standard methods for determining the TPC of frying oil samples are labor‐intensive and require toxic chemicals. The volatile compounds determined by FGC E‐nose show a good linear relationship with TPC in frying rapeseed oil samples. The FGC E‐nose technique is suitable to monitor the frying process and the proposed method has the potential to be a more rapid and convenient tool for quality control of frying oils.

A flash gas chromatography electronic nose (FGC E‐nose) is applied to measure flavor quality changes and monitor the oxidation process of rapeseed oils during frying. Partial least squares regression is applied to determine the relationship between total polar compounds and some volatile compounds determined by FGC E‐nose in frying rapeseed oils.
Combination of Hydrophilic or Lipophilic Natural Compounds to Improve the Oxidative Stability of Flaxseed Oil
Authors: Roschel Gabriela Grassmann , Silveira Tayse Ferreira Ferreira da , Cajaiba Letícia Maeda , Castro Inar Alves
Published: February 2019

Oxidation of bulk oils involves radical molecules, transitions metals, and association colloids, among other factors. Combining mechanistically different antioxidants is one possible strategy to improve oxidative stability of polyunsaturated fatty acids rich oils. However, antioxidant polarity may play a critical role in the oxidative protection efficacy. Thus, the objective of this study is to formulate a hydrophilic mixture (HM) containing sinapic, ascorbic, and citric acid; and a lipophilic mixture (LM) composed of α‐tocopherol, ascorbyl palmitate, and citric acid; and apply these mixtures in crude, and stripped flaxseed oils. The oxidative stability of crude oil samples containing HM and LM is comparable to that of artificial compounds mixture (ethylenediamine tetraacetic acid [EDTA] and terc‐butyl hydroquinone [TBHQ]). HM is more effective than LM in crude oil, but not in stripped oil, suggesting a strong influence of minor components on antioxidant activity of natural compounds.

Practical Applications: The increasing demand for foods containing polyunsaturated fatty acids (PUFA) brings the challenge of their chemical stabilization. Here, a strategic mixture of hydrophilic natural antioxidants is effective to stabilize flaxseed oil, with effectiveness comparable to that of artificial antioxidants. Therefore, this HM constitutes a feasible and efficient option to be applied by food producers, especially in formulations that present a health claim.
Mycophenolic Acid: Biogenesis, Compound Isolation, Biological Activity, and Historical Advances in Total Synthesis
Authors: Halle Mahesh B. , Lee Woohyun , Yudhistira Tesla , Kim Myungseob , Churchill David G.
Published: February 2019

The 6‐alkyl‐2,4‐dihydroxybenzoate moiety known commonly as resorcylate occurs widely as a building block in various fused cyclic systems of bioactive natural products and analogues. Among these many isolated active molecules, mycophenolic acid (MPA) was one of the most studied for its structural features and its potential biological activity. This perspective article portrays the unique biosynthetic interrelationships of polyketide formations in to resorcylates, which are implemented by recent biomimetic/chemical synthetic investigations of the natural product target. The resorcylate, MPA have remained as interesting targets for total synthesis in many laboratories worldwide. There are 13 syntheses reported for MPA to date (Scifinder search). The synthetic strategies for this potential lead compound was an evolution of various methods from generating the highly‐substituted aromatic system via employing simple and commercially available materials to the catalytic methods employed which always involve linear sequences; convergent approaches to the most important protecting group‐free syntheses are also briefly documented in this critical review. This natural product has been the subject of considerable synthetic study. Most reported total syntheses employ 6‐alkyl‐2,4‐hydroxybenzoic acids (lactones) as intermediates and proceed via stepwise derivatization to introduce other functionalities.
A multiplex SNP genotyping by allele‐specificspecific PCR based on stem‐loop and universal fluorescent primers of Chr1daxin mice
Authors: Wang Maochun , Xu Fuyi , Chen Ke , Li Xiaoning , Li Kai , Zhou Yuxun , Xiao Junhua
Published: February 2019

Single nucleotide polymorphisms (SNPs) are one of the most common markers in mammals. Rapid, accurate, and multiplex typing of SNPs is critical for subsequent biological and genetic research. In this study, we have developed a novel method for multiplex genotyping SNPs in mice. The method involves allele‐specific PCR amplification of genomic DNA with two stem‐loop primers accompanied by two different universal fluorescent primers. Blue and green fluorescent signals were conveniently detected on a DNA sequencer. We verified four SNPs of 65 mice based on the novel method, and it is well suited for multiplex genotyping as it requires only one reaction per sample in a single tube with multiplex PCR. The use of universal fluorescent primers greatly reduces the cost of designing different fluorescent probes for each SNP. Therefore, this method can be applied to many biological and genetic studies, such as multiple candidate gene testing, genome‐wide association study, pharmacogenetics, and medical diagnostics.
Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
Authors: Auvin Stéphane , Williams Betsy , McMurray Rob , Kumar Dinesh , Perdomo Carlos , Malhotra Manoj
Published: February 2019

Objective

Drug development for patients with Lennox‐Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure efficacy parameters related to QoL in pediatric patients with LGS, using seizure diary data from rufinamide Study 303 (NCT01405053).

Methods

Study 303 was a phase III, multicenter, randomized, controlled, open‐label study involving patients aged ≥1 to <4 years with inadequately controlled LGS. Patients were randomized 2:1 to receive add‐on therapy with rufinamide or any other approved antiseizure drug (ASD), in addition to their existing treatment of 1‐3 ASDs, across a 106‐week treatment phase. Seizure diaries, completed by parents or caregivers, recorded seizure occurrence, and were used in this post hoc analysis to evaluate two novel efficacy parameters comparing baseline vs postbaseline mean number of seizure‐free days and assessing time to reach the number of prerandomization seizures for patients receiving rufinamide or any other ASD.

Results

Patients received rufinamide (n = 25) or any other ASD (n = 12). For rufinamide, mean number of seizure‐free days was 42.2% greater postbaseline compared with baseline (P < 0.0001); only one rufinamide patient experienced a decrease in number of seizure‐free days postbaseline. Median time to reach the baseline number of seizures increased by 10.5 days for rufinamide and 0.5 days for the any‐other‐ASD group during the treatment phase, to 46.0 and 54.0 days, respectively.

Significance

Both of these novel and contrasting endpoints demonstrated potential improvements in seizure outcomes in patients receiving rufinamide postbaseline vs baseline. Although these parameters should be investigated in larger patient populations, our initial findings suggest that they could be applied as predefined primary endpoints for seizure assessment in future clinical trials for LGS drug development.
Cost analysis of carbon capture and storage for current gas‐fired power plants in Nigeria
Authors: Ugwuishiwu Boniface O. , Nwakaire Joel N. , Ohagwu Chukwuemeka J.
Published: February 2019

This study examined the cost of adopting carbon capture and storage (CCS) as a technology when retrofitting current gas‐fired plants in Nigeria to reduce CO2 emissions. Studies show that Nigeria has abandoned or depleted oil fields; it has large coal reserves that are potential sites for CO2 storage. Five power plants with capacities of 1074, 675, 624, 480, and 191 MW were studied using the Integrated Environmental Control Model (IECM) 9.5. The IECM 9.5 was calibrated using available data and some default values to model the performance and cost of retrofitting the power plants. The transport and storage system chosen was pipeline and enhance oil recovery (EOR). The results show that net plant efficiency, CO2 emission rate, quantity of CO2 captured, and CCS energy penalty are 35.78 ± 1.69%, 0.0668 ± 0.0138 kg MWh−1, 0.4478 ± 0.0274 kg MWh−1, and 0.2588 ± 0.0386%, respectively. The results also show that total capital requirement, cost of electricity, and percentage increase in cost of electricity were 1888.2 ± 336.9 $ kW−1, 114.44 ± 10.15 $ MWh−1, and 52.04 ± 3.58%, respectively. In the same manner, the cost of CO2 avoided, cost of capture, and added cost of CCS were 84.442 ± 27.73 $ MWh−1, 60.02 ± 22.51 $ tonne−1, and 28.44 ± 10.16 $ MWh−1, respectively. Further analysis shows that it would be advantageous to retrofit 1074 MW plants because this has a 46.51% increase in cost, which is lower than the cost for the other retrofitted plants. The total CO2 emission rate dropped from 0.4282 ± 0.014 to 0.0668 ± 0.0138 kg MWh−1; this drop is significant as it shows that CCS can reduce the amount of CO2 emitted from Nigeria. The study recommends that CCS is a viable CO2 emission‐reduction alternative but incentives must be put in place to cushion the high cost of electricity. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Social Media, E‐Health, and Medical Ethics
Authors: Terrasse Mélanie , Gorin Moti , Sisti Dominic
Published: February 2019

Given the profound influence of social media and emerging evidence of its effects on human behavior and health, bioethicists have an important role to play in the development of professional standards of conduct for health professionals using social media and in the design of online systems themselves. In short, social media is a bioethics issue that has serious implications for medical practice, research, and public health. Here, we inventory several ethical issues across four areas at the intersection of social media and health: the impact of social networking sites on the doctor‐patient relationship, the development of e‐health platforms to deliver care, the use of online data and algorithms to inform health research, and the broader public health consequences of widespread social media use. In doing so, we review discussions of these topics and emphasize the need for bioethics to focus more deeply on the ways online technology platforms are designed and implemented. We argue that bioethicists should turn their attention to the ways in which consumer engagement, bias, and profit maximization shape online content and, consequently, human behavior and health. We also offer a set of recommendations and suggest future directions for addressing ethical challenges in these domains.
Searching for the neurite density with diffusion MRI: Challenges for biophysical modeling
Authors: Lampinen Björn , Szczepankiewicz Filip , Novén Mikael , van Westen Danielle , Hansson Oskar , Englund Elisabet , Mårtensson Johan , Westin Carl‐Fredrik , Nilsson Markus
Published: February 2019

In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic (“stick‐like”) diffusion. Second, the “density” of tissue components may be confounded by non‐diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with “b‐tensor encoding” and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b‐tensor data is associated with myelinated axons but not with dendrites. Furthermore, b‐tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data‐driven estimates of compartment‐specific T2 values. Finally, the “stick” fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment‐specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained “index” parameters could be valid within limited domains that should be delineated by future studies.
Detection of mild cognitive impairment in a community‐dwelling population using quantitative, multiparametric MRI‐based classification
Authors: Bouts Mark J. R. J. , van der Grond Jeroen , Vernooij Meike W. , Koini Marisa , Schouten Tijn M. , de Vos Frank , Feis Rogier A. , Cremers Lotte G. M. , Lechner Anita , Schmidt Reinhold , de Rooij Mark , Niessen Wiro J. , Ikram M. Arfan , Rombouts Serge A. R. B.
Published: February 2019

Early and accurate mild cognitive impairment (MCI) detection within a heterogeneous, nonclinical population is needed to improve care for persons at risk of developing dementia. Magnetic resonance imaging (MRI)‐based classification may aid early diagnosis of MCI, but has only been applied within clinical cohorts. We aimed to determine the generalizability of MRI‐based classification probability scores to detect MCI on an individual basis within a general population. To determine classification probability scores, an AD, mild‐AD, and moderate‐AD detection model were created with anatomical and diffusion MRI measures calculated from a clinical Alzheimer's Disease (AD) cohort and subsequently applied to a population‐based cohort with 48 MCI and 617 normal aging subjects. Each model's ability to detect MCI was quantified using area under the receiver operating characteristic curve (AUC) and compared with an MCI detection model trained and applied to the population‐based cohort. The AD‐model and mild‐AD identified MCI from controls better than chance level (AUC = 0.600, p = 0.025; AUC = 0.619, p = 0.008). In contrast, the moderate‐AD‐model was not able to separate MCI from normal aging (AUC = 0.567, p = 0.147). The MCI‐model was able to separate MCI from controls better than chance (p = 0.014) with mean AUC values comparable with the AD‐model (AUC = 0.611, p = 1.0). Within our population‐based cohort, classification models detected MCI better than chance. Nevertheless, classification performance rates were moderate and may be insufficient to facilitate robust MRI‐based MCI detection on an individual basis. Our data indicate that multiparametric MRI‐based classification algorithms, that are effective in clinical cohorts, may not straightforwardly translate to applications in a general population.
PNPLA3, CGI‐58, and Inhibition of Hepatic Triglyceride Hydrolysis in Mice
Authors: Wang Yang , Kory Nora , BasuRay Soumik , Cohen Jonathan C. , Hobbs Helen H.
Published: February 2019

A variant (148M) in patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) is a major risk factor for fatty liver disease. Despite its clinical importance, the pathogenic mechanism linking the variant to liver disease remains poorly defined. Previously, we showed that PNPLA3(148M) accumulates to high levels on hepatic lipid droplets (LDs). Here we examined the effect of that accumulation on triglyceride (TG) hydrolysis by adipose triglyceride lipase (ATGL), the major lipase in the liver. As expected, overexpression of ATGL in cultured hepatoma (HuH‐7) cells depleted the cells of LDs, but unexpectedly, co‐expression of PNPLA3(wild type [WT] or 148M) with ATGL inhibited that depletion. The inhibitory effect of PNPLA3 was not caused by the displacement of ATGL from LDs. We tested the hypothesis that PNPLA3 interferes with ATGL activity by interacting with its cofactor, comparative gene identification‐58 (CGI‐58). Evidence supporting such an interaction came from two findings. First, co‐expression of PNPLA3 and CGI‐58 resulted in LD depletion in cultured cells, but expression of PNPLA3 alone did not. Second, PNPLA3 failed to localize to hepatic LDs in liver‐specific Cgi‐58 knockout (KO) mice. Moreover, overexpression of PNPLA3(148M) increased hepatic TG levels in WT, but not in Cgi‐58 KO mice. Thus, the pro‐steatotic effects of PNPLA3 required the presence of CGI‐58. Co‐immunoprecipitation and pulldown experiments in livers of mice and in vitro using purified proteins provided evidence that PNPLA3 and CGI‐58 can interact directly. Conclusion: Taken together, these findings are consistent with a model in which PNPLA3(148M) promotes steatosis by CGI‐58‐dependent inhibition of ATGL on LDs.
A Call to Standardize Definitions, Data Collection, and Outcome Assessment to Improve Care in Alcohol‐Related Liver Disease
Authors: Shen Nicole T. , Salajegheh Annaheta , Brown Robert S.
Published: February 2019

Alcohol‐related liver disease (ALD) is highly prevalent and appears to be increasingly reported with worsening mortality; thus, optimizing care in this patient population is imperative. This will require a multidisciplinary, multifaceted approach that includes recognizing alcohol use disorder (AUD) and existing treatments for AUD. We must also acknowledge the full spectrum of ALD clinically and histologically. For example, our current clinical definitions of alcohol‐related hepatitis (AH) do not address that >95% of severe AH occurs in the setting of cirrhosis with <60% of liver explants having hepatitis. Given that the majority of ALD studies rely on clinical diagnosis and lack pathologic confirmation, prior data on the efficacy of medical treatment or use of transplantation are likely limited by intertrial and intratrial heterogeneity. Added limitations of the current field include the inconsistent reporting of relapse with the use of varying definitions and unreliable assessments. Moreover, studies fail to consistently capture the data variables that likely influence the main outcomes of interest in this population—mortality and relapse—and a global effort to create a standardized data collection tool moving forward could help effectively and efficiently aid in the advancement of this field. Conclusion: To optimize patient care and make best use of a limited resource, a systematic change in the approach to research in this population must be undertaken that creates consistent definitions for use in future research to generate reliable and reproducible results. With this in mind, we concisely reviewed the literature to summarize the current state of treating and managing ALD, the heterogeneity in definitions, and the significant opportunities for clinical and research improvement.
NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis
Authors: Harrison Stephen A. , Rossi Stephen J. , Paredes Angelo H. , Trotter James F. , Bashir Mustafa R. , Guy Cynthia D. , Banerjee Rajarshi , Jaros Mark J. , Owers Sandra , Baxter Bryan A. , Ling Lei , DePaoli Alex M.
Published: February 2019

NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double‐blind, placebo‐controlled study in patients with biopsy‐confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open‐label study, we assessed the histological efficacy of NGM282 in patients with biopsy‐confirmed nonalcoholic steatohepatitis. Paired liver biopsies from 43 patients who received subcutaneous NGM282 (1 mg, n = 24; 3 mg, n = 19) once daily for 12 weeks were evaluated blinded to time point, subject, and clinical information. At week 12, NGM282 significantly reduced nonalcoholic fatty liver disease activity score (NAS; −1.9; 95% confidence interval, −2.6 to −1.2; P < 0.001 in the 1 mg group; −2.2, −3.1 to −1.3; P < 0.001 in the 3 mg group) and fibrosis (−0.5; −0.9 to 0; P = 0.035 in the 3 mg group) scores. Overall, 50% and 63% of the patients receiving NGM282 1 mg or 3 mg, respectively, improved NAS by 2 or more points without fibrosis worsening. Of the patients receiving NGM282 1 mg or 3 mg, 25% and 42%, respectively, improved liver fibrosis by one stage or more without worsening of steatohepatitis. Treatment with NGM282 led to relative reductions in liver fat content (−58% and −67% in the 1 mg and 3 mg groups, respectively), corrected T1 (cT1; −8% and −9%), alanine aminotransferase (ALT) (−67% and −60%), aspartate aminotransferase (−57% and −52%), and fibrogenesis biomarkers neoepitope‐specific N‐terminal propeptide of type III collagen (Pro‐C3; −22% and −33%) and enhanced liver fibrosis score (ELF; −3% and −6%) at week 12. Greater reductions in Pro‐C3, ELF, and cT1, but not in liver fat content, 7alpha‐hydroxy‐4‐cholesten‐3‐one, or ALT, were observed in histological responders than in nonresponders. Conclusion: In this open‐label study, NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and fibrosis scores, accompanied by improvements in noninvasive imaging and serum markers.
Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis
Authors: Abe Kazumichi , Takahashi Atsushi , Fujita Masashi , Hayashi Manabu , Okai Ken , Nozawa Yoshihiro , Ohira Hiromasa
Published: February 2019

Interleukin (IL)‐33 was recently described as a new member of the IL‐1 family; members of this family have proinflammatory activity. IL‐33 and its soluble receptor ST2 (sST2) have been implicated in the pathogenesis of autoimmune diseases. This study investigated serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) and the relationship of these molecules with clinical and pathologic parameters. Subjects included 65 patients with AIH who were diagnosed in our hospital. The control population included 17 healthy individuals and 36 patients with primary biliary cholangitis (PBC). Mean age at AIH diagnosis was 55.5 years, and the male‐to‐female ratio was 6:59. Serum IL‐33 and sST2 levels were significantly higher in patients with AIH than in those with PBC or controls. Importantly, immunohistochemistry revealed high IL‐33 expression in liver sections from patients with AIH. In particular, serum IL‐33 and sST2 levels were significantly higher in acute‐onset AIH than in chronic‐onset AIH. Serum IL‐33 levels were positively correlated with serum total bilirubin (TB), alanine aminotransferase (ALT), and necroinflammatory activity in AIH. We performed multivariate logistic regression analysis and found serum IL‐33 levels to be independent factors for severe activity. Serum sST2 levels were positively correlated with serum TB and ALT and negatively correlated with serum albumin and prothrombin time in AIH. In particular, serum sST2 levels were significantly higher in severe symptoms of AIH. Serum IL‐33 and sST2 levels in patients with AIH responsive to treatment with prednisolone were significantly decreased after treatment. Interestingly, serum IL‐33 level was associated with a significantly increased risk of relapse. Conclusion: IL‐33/ST2 may play an important role in the pathogenesis and severity of AIH and may be a promising target for AIH therapy.