bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPK promotes the survival of colorectal cancer stem cells
Authors: Guo Bing , Han Xin , Tkach Diane , Huang Shu‐Guang , Zhang Dong
Published: July 2018

Background

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis, chemotherapy resistance, and relapse.

Methods

To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient‐derived xenograft (PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent‐activated cell sorting (FACS) and characterized their metabolic properties.

Results

Interestingly, we found that the CRC cancer stem cells (ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species (ROS) than non‐CRC cancer stem cells (ie, CRC cells with lower ALDH activity, or ALDH−). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly, we observed higher AMP‐activated protein kinase (AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.

Conclusion

We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.
The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models
Authors: Gong Shu‐ran , Bao Lin‐lin
Published: July 2018

In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.
Safety considerations for working with animal models involving human health hazards
Authors: Carpenter Calvin B.
Published: July 2018

A human health hazard may constitute a variety of hazards that are encountered in an animal facility. Health hazards include physical, chemical, radioactive, or biological hazards such as cage and rack washers, chemicals used for cleaning and disinfection, experimental drugs or biologics, radioactive isotopes, zoonotic diseases, allergens, experimental infectious agents, or biological toxins. This article will focus on experimental infectious agents and biological toxins (biohazards) that are hazardous to both animals and humans and require biological containment (biocontainment) to prevent their inadvertent release into the environment. Key areas for safely managing a biocontainment animal care and use program and vivarium are described. While scientific research involving health hazards has created some challenges, it has also provided some excellent advances in methods and technologies. The ideas and approaches in this article will be useful for those just entering this field of research and those who have committed their careers to the safe use of animals exposed to biohazards.
Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions
Authors: Deng Xiaoyun , Rong Jian , Wang Lu , Vasdev Neil , Zhang Lei , Josephson Lee , Liang Steven H.
Published: July 2018

Positron emission tomography (PET) is a molecular imaging technology that provides quantitative information about function and metabolism in biological processes in vivo for disease diagnosis and therapy assessment. The broad application and rapid advances of PET has led to an increased demand for new radiochemical methods to synthesize highly specific molecules bearing positron‐emitting radionuclides. This Review provides an overview of commonly used labeling reactions through examples of clinically relevant PET tracers and highlights the most recent developments and breakthroughs over the past decade, with a focus on 11C, 18F, 13N, and 15O.
Highly Chemo‐ and Stereoselective Catalyst‐Controlled Allylic C−H Insertion and Cyclopropanation Using Donor/Donor Carbenes
Authors: Zhu Dong , Chen Lianfen , Zhang He , Ma Zhiqiang , Jiang Huanfeng , Zhu Shifa
Published: July 2018

The highly chemo‐, enantio‐, and diastereoselective catalyst‐controlled intramolecular allylic C−H insertion and cyclopropanation of donor/donor carbenes are reported. The RuII/Pybox complex selectively catalyzed the intramolecular allylic C−H insertion, providing vinyl‐substituted dihydroindoles with greater than 20:1 chemoselectivity and up to greater than 99 % ee. Chiral dirhodium(II) tetracarboxylates, however, selectively promoted the intramolecular cyclopropanation, giving rise to cyclopropane‐fused tetrahydroquinoline derivatives in excellent yields with greater than 99:1 chemoselectivity and up to 97 % ee.
Testing predictions for symmetry, variability and chronology of backed artefact production in Australia's Western Desert
Authors: MCDONALD JO , REYNEN WENDY , FULLAGAR RICHARD
Published: July 2018

The “Backed Artefact Symmetry Index” (BASI) provides a measure with which to describe geometric variation in Australian backed artefacts, and Peter Hiscock has suggested that desert versions of this artefact type will be more symmetrical than their coastal counterparts. The re‐excavated Serpent's Glen (Karnatukul) site and nearby site of Wirrili have produced a large assemblage of backed artefacts. These Western Desert assemblages allow for the testing of BASI. The backed artefacts demonstrate significantly more variability than predicted, demonstrating that all technological debates benefit from larger well‐dated assemblages. The signalling information observed in these sites’ pigment art repertoires, combined with this versatility in the toolkits, increases our understanding of the complexity of middle and late Holocene highly mobile foragers in the Australian arid zone.
Investigating drug–disease interactions in drug–symptom–disease triples via citation relations
Authors: Song Min , Kang Keunyoung , Young An Ju
Published: July 2018

With the growth in biomedical literature, the necessity of extracting useful information from the literature has increased. One approach to extracting biomedical knowledge involves using citation relations to discover entity relations. The assumption is that citation relations between any two articles connect knowledge entities across the articles, enabling the detection of implicit relationships among biomedical entities. The goal of this article is to examine the characteristics of biomedical entities connected via intermediate entities using citation relations aided by text mining. Based on the importance of symptoms as biomedical entities, we created triples connected via citation relations to identify drug–disease pairs with shared symptoms as intermediate entities. Drug–disease interactions built via citation relations were compared with co‐occurrence‐based interactions. Several types of analyses were adopted to examine the properties of the extracted entity pairs by comparing them with drug–disease interaction databases. We attempted to identify the characteristics of drug–disease pairs through citation relations in association with biomedical entities. The results showed that the citation relation‐based approach resulted in diverse types of biomedical entities and preserved topical consistency. In addition, drug–disease pairs identified only via citation relations are interesting for clinical trials when they are examined using BITOLA.
Citations in Scientific Texts: Do Social Relations Matter?
Authors: Milard Béatrice , Tanguy Ludovic
Published: July 2018

This article presents an investigation of the role of social relations in the writing of scientific articles through the study of in‐text citations. Does the fact that the author of an article knows the author whose work he or she cites have an impact on the context of the citation? Because citations are commonly used as criteria for research evaluation, it is important to question their social background to better understand how it impacts textual features. We studied a collection of science articles (N = 123) from 5 disciplines and interviewed their authors (N = 84) to: (a) identify the social relations between citing and cited authors; and (b) measure the correlation between a set of features related to in‐text citations (N = 6,956) and the identified social relations. Our pioneering work, mixing sociological and linguistic results, shows that social relations between authors can partly explain the variations of citations in terms of frequency, position and textual context.
Generalized prediction intervals for treatment effects in random‐effects models
Authors: Al‐Sarraj Razaw , von Brömssen Claudia , Forkman Johannes
Published: July 2018

This article derives generalized prediction intervals for random effects in linear random‐effects models. For balanced and unbalanced data in two‐way layouts, models are considered with and without interaction. Coverage of the proposed generalized prediction intervals was estimated in a simulation study based on an agricultural field experiment. Generalized prediction intervals were compared with prediction intervals based on the restricted maximum likelihood (REML) procedure and the approximate methods of Satterthwaite and Kenward and Roger. The simulation study showed that coverage of generalized prediction intervals was closer to the nominal level 0.95 than coverage of prediction intervals based on the REML procedure.
Use of synthesized analysis and informed treatment to promote school reintegration
Authors: Taylor Sarah A. , Phillips Katrina J. , Gertzog Margaret G.
Published: July 2018

Severe problem behavior within a school can result in exclusion from education. A practitioner providing school‐based services must plan an effective treatment, while mitigating safety risks to the child and others. In this study, we sought to replicate the interview‐informed synthesized contingency analysis and treatment procedures developed by Hanley and colleagues in a school setting for a 12‐year‐old boy with autism and severe problem behavior. However, due to a severe burst in behavior, we increased treatment intensity and introduced procedures across increasing academic demand contexts to promote safety. During a treatment extension, procedures were implemented by teacher aides, across the entire school day. Treatment resulted in meaningful reductions in problem behavior, sustained improvements in compliance, and the student was fully integrated into the regular classroom. In addition, improvements in functional communication and tolerance persisted across contexts and the intervention received high social validity scores from those involved.
Late recovery from unconsciousness in a patient with severe posterior reversible encephalopathy syndrome
Authors: Ogura Shiori , Narumiya Hiromichi , Iiduka Ryoji , Nagakane Yoshinari
Published: July 2018

Key Clinical Message

This study describes a patient case presenting with severe posterior reversible encephalopathy syndrome (PRES) who needed 3 months to recover impaired consciousness. We discuss the protracted time course needed to deal with severe PRES cases. Positive prognoses can emerge from these situations if treatment is prompt and precise.
Efficient N‐Heterocyclic Carbene/Ruthenium Catalytic Systems for the Alcohol Amidation with Amines: Involvement of Poly‐Carbene Complexes?
Authors: Cheng Hua , Xiong Mao‐Qian , Zhang Ni , Wang Hua‐Jing , Miao Yang , Su Wei , Yuan Ye , Chen Cheng , Verpoort Francis
Published: July 2018

The atom‐economic direct amidation of alcohols with amines has been recently highlighted as an attractive and promising transformation. Among the versatile reported catalytic systems, in situ generated N‐heterocyclic carbene (NHC)/ruthenium (Ru) catalytic systems have demonstrated their advantages such as easy operation and use of commercial Ru compounds. However, the existing catalyst loadings are relatively high, and additional insights for the in situ catalyst generation are still not well‐documented. In this work, a variety of benzimidazole‐based NHC precursors were initially synthesized. Through the screening of various NHC precursors and other reaction conditions, active in situ catalytic systems were discovered for the efficient amide synthesis. Notably, the catalyst loading is as low as 0.5 mol %. Furthermore, additional experiments were performed to validate the rationale for the superiority of the current catalytic systems over our previous system. It was observed that the ligand structure is one of the reasons for the higher activity. In addition, the higher ratio of the NHC precursor/[Ru] is another important factor for the improvement. Further HR‐MS analysis identified the formation of two mono‐NHC‐Ru species as major species and two Ru species bearing multiple NHC ligands as minor species. Hopefully, the efficient and readily‐accessible catalytic systems reported herein could demonstrate great potential for further practical applications.
Stable Organic Radicals Derived from N‐Heterocyclic Carbenes
Authors: Kim Youngsuk , Lee Eunsung
Published: July 2018

Over the past decade, numerous stable organic and main‐group radicals have been synthesized from N‐heterocyclic carbenes (NHCs). The structure of NHCs, in particular, offers electronic stabilization that helps to delocalize the unpaired electron over the molecule. In addition, the sterically bulky substituents of NHCs protect the radical center to prevent detrimental reactions such as dimerization. These advantages enable the straightforward synthesis and characterization of various interesting organic radicals starting from NHCs, which are, these days, widely available. NHCs have enabled the structural characterization of various organic radicals over the past decade, including α‐carbonyl, propargyl, oxyallyl, and triazenyl radicals as notable examples. This minireview summarizes the advances in this field, mainly focusing on the preparation and stability as well as the properties and applications of NHC‐derived organic radicals.
Is ventricular sensing always right, when it is left?
Authors: Biffi Mauro , de Zan Giulia , Massaro Giulia , Angeletti Andrea , Martignani Cristian , Boriani Giuseppe , Diemberger Igor , Ziacchi Matteo
Published: July 2018

Background

Ventricular sensing in transvenous cardiac implantable electronic devices (CIEDs) occurs conventionally from the right ventricular (RV) channel, though it evolved from epicardial sensing both in pacemakers and implantable cardioverter‐defibrillators (ICDs).

Hypothesis

The objective of this study was to observe the reliability of left ventricular (LV) sensing by transvenous leads placed in coronary veins.

Methods

LV leads were used for sensing and arrhythmia detection in clinical situations where placement of an RV lead across the tricuspid valve was either not preferred or not feasible, or RV signal was unsuitable for arrhythmia detection, or in the event of sensing failure of an RV lead under advisory in cardiac resynchronization therapy defibrillator (CRTD) recipients.

Results

Thirty‐seven patients had an IS‐1 LV lead connected to the RV port of CIEDs (17 pacemakers, 5 cardiac resynchronization therapy pacemaker [CRTP], 2 ICDs, and 13 CRTDs). Along a median 41 (25‐67) months follow‐up, lead performance remained stable; there were neither undersensing nor oversensing of non‐cardiac signals. VT/VF were correctly detected and terminated by ATP and shocks (one and three patients, respectively); no inappropriate arrhythmia detection. Device reprogramming occurred in four CRTD recipients because of transient counting the QRS (short intervals) when paced in LV‐only, and in two with T‐wave oversensing.

Conclusions

Ventricular sensing by an LV lead is feasible in transvenous devices. Sensing programmability is an unmet need: to fix RV lead sensing issues in cardiac resynchronization therapy (CRT) recipients at no risk of infection (no pocket opening); to avoid interaction with the tricuspid valve; to avoid lead redundancy in the vasculature. Moreover, it will be mandatory owing to the loss of lead interchangeability due to the adoption of DF‐4 and quadripolar leads.
Molecular Photoswitching Aided by Excited‐State Aromaticity
Authors: Durbeej Bo , Wang Jun , Oruganti Baswanth
Published: July 2018

Central to the development of optoelectronic devices is the availability of efficient synthetic molecular photoswitches, the design of which is an arena where the evolving concept of excited‐state aromaticity (ESA) is yet to make a big impact. The aim of this minireview is to illustrate the potential of this concept to become a key tool for the future design of photoswitches. The paper starts with a discussion of challenges facing the use of photoswitches for applications and continues with an account of how the ESA concept has progressed since its inception. Then, following some brief remarks on computational modeling of photoswitches and ESA, the paper describes two different approaches to improve the quantum yields and response times of switches driven by E/Z photoisomerization or photoinduced H‐atom/proton transfer reactions through simple ESA considerations. It is our hope that these approaches, verified by quantum chemical calculations and molecular dynamics simulations, will help stimulate the application of the ESA concept as a general tool for designing more efficient photoswitches and other functional molecules used in optoelectronic devices.
Effective Guest Inclusion by a 6‐O‐Modified β‐Cyclodextrin Dimer in Organic Solvents
Authors: Asahara Chizuru , Iwamoto Takuya , Akashi Mitsuru , Shigemitsu Hajime , Kida Toshiyuki
Published: July 2018

A 6‐O‐tert‐butyldimethylsilylated β‐cyclodextrin (TBDMS‐β‐CD) dimer, in which two TBDMS‐β‐CD rings are connected in a head‐to‐head fashion by a m‐xylylene linker, effectively forms inclusion complexes with pyrene and naphthalene in nonpolar organic solvents such as cyclohexane and benzene. This TBDMS‐β‐CD dimer shows a higher inclusion ability toward these guests than a TBDMS‐β‐CD dimer bearing a p‐xylylene linker due to the greater cooperation of the two TBDMS‐β‐CD rings for the guest inclusion. Unlike the corresponding monomer, the TBDMS‐β‐CD dimer bearing a m‐xylylene linker is also a good host even in polar organic solvents such as tetrahydrofuran. High chiral recognition of aromatic amines and alcohol is realized by utilizing inclusion within the cavity of the TBDMS‐β‐CD dimer in cyclohexane. In particular, an extremely high binding selectivity for (S)‐1‐(1‐naphthyl)ethylamine and (S)‐1‐(1‐naphthyl)ethanol over the corresponding (R)‐isomers is achieved. Moreover, by utilizing the high chiral recognition with the TBDMS‐β‐CD dimer in cyclohexane, a non‐enzymatic kinetic resolution of racemic 1‐(1‐naphthyl)ethylamine via enantioselective N‐benzoylation is attained with an enantiomer excess of up to 87 % and an s‐factor of 15.
The KHENERGY Study: Safety and Efficacy of KH176 in Mitochondrial m.3243A>G Spectrum Disorders
Authors: Janssen Mirian C.H. , Koene Saskia , de Laat Paul , Hemelaar Pleun , Pickkers Peter , Spaans Edwin , Beukema Rypko , Beyrath Julien , Groothuis Jan , Verhaak Chris , Smeitink Jan
Published: July 2018

KH176 is a potent intracellular reduction–oxidation‐modulating compound developed to treat mitochondrial disease. We studied tolerability, safety, pharmacokinetics, pharmacodynamics, and efficacy of twice daily oral 100 mg KH176 for 28 days in a double‐blind, randomized, placebo‐controlled, two‐way crossover phase IIA study in 18 adult m.3243A>G patients without cardiovascular involvement. Efficacy parameters included clinical and functional outcome measures and biomarkers. The trial was registered within ClinicalTrials.gov (NCT02909400), the European Clinical Trials Database (2016‐001696‐79), and ISRCTN (43372293) (The KHENERGY study). Twice daily oral 100 mg KH176 was well tolerated and appeared safe. No serious treatment‐emergent adverse events were reported. No significant improvements in gait parameters or other outcome measures were obtained, except for a positive effect on alertness and mood, although a coincidence due to multiplicity cannot be ignored. The results of the study provide first data on safety and efficacy of KH176 in patients with mitochondrial disease and will be instrumental in designing future clinical trials.
Provable secure lightweight hyper elliptic curve‐based communication system for wireless sensor networks
Authors: Naresh Vankamamidi S. , Sivaranjani Reddi , V.E.S. Murthy Nistala
Published: July 2018

It is widely believed that hyper elliptic curve cryptosystems (HECCs) are not attractive for wireless sensor network because of their complexity compared with systems based on lower genera, especially elliptic curves. Our contribution shows that for low cost security applications HECs cryptosystems can outperform elliptic curve cryptosystems. The aim of this paper is to propose a discrete logarithm problem‐based lightweight secure communication system using HEC. We propose this for different genus curves over varied prime fields performing a full scale study of their adaptability to various types of constrained networks. Also, we propose to evaluate the performance of the protocol for computational times with respect to different genus for main operations like Jacobian, Divisor identifications, key generation, signature generation/verification, message encryption, and decryption by changing the size of the field. A formal security model was established based on the hardness of HEC‐Decision Diffie‐Hellman (HEC‐DDH). Finally, a comparative analysis with ECC‐based cryptosystems was made, and satisfactory results were obtained.
Repeated range expansion and niche shift in a volcanic hotspot archipelago: Radiation of C4 Hawaiian Euphorbia subgenus Chamaesyce (Euphorbiaceae)
Authors: Yang Ya , Morden Clifford W. , Sporck‐Koehler Margaret J. , Sack Lawren , Wagner Warren L. , Berry Paul E.
Published: July 2018

Woody perennial plants on islands have repeatedly evolved from herbaceous mainland ancestors. Although the majority of species in Euphorbia subgenus Chamaesyce section Anisophyllum (Euphorbiaceae) are small and herbaceous, a clade of 16 woody species diversified on the Hawaiian Islands. They are found in a broad range of habitats, including the only known C4 plants adapted to wet forest understories. We investigate the history of island colonization and habitat shift in this group. We sampled 153 individuals in 15 of the 16 native species of Hawaiian Euphorbia on six major Hawaiian Islands, plus 11 New World close relatives, to elucidate the biogeographic movement of this lineage within the Hawaiian island chain. We used a concatenated chloroplast DNA data set of more than eight kilobases in aligned length and applied maximum likelihood and Bayesian inference for phylogenetic reconstruction. Age and phylogeographic patterns were co‐estimated using BEAST. In addition, we used nuclear ribosomal ITS and the low‐copy genes LEAFY and G3pdhC to investigate the reticulate relationships within this radiation. Hawaiian Euphorbia first arrived on Kaua`i or Ni`ihau ca. 5 million years ago and subsequently diverged into 16 named species with extensive reticulation. During this process Hawaiian Euphorbia dispersed from older to younger islands through open vegetation that is disturbance‐prone. Species that occur under closed vegetation evolved in situ from open vegetation of the same island and are only found on the two oldest islands of Kaua`i and O`ahu. The biogeographic history of Hawaiian Euphorbia supports a progression rule with within‐island shifts from open to closed vegetation.
Increased female resistance to mating promotes the effect of mechanical constraints on latency to pair
Authors: Han Chang S. , Jablonski Piotr G.
Published: July 2018

Size‐assortative mating, defined as a positive linear association of body size between members of mating pairs, can arise from mechanical constraints on pairing efficiency, particularly when mating success is affected by males’ mate‐grasping force. In this context, female resistance is predicted to have an important role in changing the threshold force necessary for males to hold females, thereby contributing to the effect of mechanical constraints. Thus, increased female resistance is expected to increase the paring success of an optimally sized male relative to the female body size (sexual size ratio = male body size/female body size = 0.86), which leads to positive size‐assortative mating. However, very little is known about the extent to which female resistance affects mechanical constraints on mate grasping. Here, using the water strider Gerris gracilicornis (Hemiptera: Gerridae), we tested whether the level of female resistance affected the relationship between the sexual size ratio and latency to pair. We found that optimally sized males mated sooner than other males when females resisted a male's mating attempts. When females did not resist, an effect of sexual size ratio on latency to pair was not found. Our results thus imply that increased female resistance to male mating attempts may strengthen the pattern of size‐assortative mating. We provide clear empirical evidence that female resistance to mating influences the effect of mechanical constraints on size‐assortative mating under sexual conflict. This result further suggests that patterns of size‐assortative mating can be altered by a variety of ecological circumstances that change female resistance to mating in many other animal species under sexual conflict.
Reproductive skipping as an optimal life history strategy in the southern elephant seal,Mirounga leonina
Authors: Griffen Blaine D.
Published: July 2018

Intermittent breeding by which organisms skip some current reproductive opportunities in order to enhance future reproductive success is a common life history trade‐off among long‐lived, iteroparous species. The southern elephant sealMirounga leoninaengages in intermediate breeding when body condition is low. While it is anticipated that this strategy may increase the lifetime reproductive output of this species, the conditions under which reproductive skipping are predicted to occur are not clear. Here I develop a dynamic state variable model based on published data that examines when southern elephant seals are predicted to optimally skip reproduction in order to maximize lifetime reproductive output as a function of current body mass, maternal age, and survivorship. I demonstrate that the optimal reproductive strategy for this species can include reproductive skipping, and that the conditions where this is optimal depend on patterns of mass‐dependent adult female survival. I further show that intermittent breeding can increase lifetime reproductive output, and that the magnitude of this benefit increases with the ability of individual animals to replenish depleted body mass through foraging. Finally, I show that when the environment is variable and foraging is reduced in bad years, the benefit of adopting an optimal strategy that includes reproductive skipping increases asymptotically with the frequency of bad years. These results highlight the importance of characterizing the pattern of adult survival in this species, as well as the need to identify other factors that may influence the prevalence and benefits of reproductive skipping.
Nanostructured Anode Materials for Non‐aqueous Lithium Ion Hybrid Capacitors
Authors: Han Cuiping , Li Hongfei , Shi Ruiying , Xu Lei , Li Junqin , Kang Feiyu , Li Baohua
Published: July 2018

The rapid advancement in electronic devices, electric vehicles, and grid storage stations have lead to a high demand for energy storage devices with enhanced power and energy densities as well as extended lifespans. Lithium ion hybrid capacitors are constructed with battery‐type anodes and capacitor‐type cathodes, which enables the direct integration of the high energy from lithium ion batteries and high power and long lifetime from supercapacitors, making lithium ion hybrid capacitor one of the most promising energy storage devices. In the past two decades, tremendous efforts have been put into the search for suitable battery‐type anode materials with improved Faradaic reaction kinetics so that it can match with the fast non‐Faradaic charging rate of the capacitive cathodes. This review aims to provide an up‐to‐date and comprehensive summary of the battery‐type anode materials for high‐performance lithium ion hybrid capacitors. To date, a large variety of battery‐type anode materials have been explored with smart material design strategies, such as carbonaceous materials, metal oxides, alloys, sulfides, nitirdes, and Mxenes, etc., which will be discussed in detail. A perspective to the challenges and future developing trends of lithium ion hybrid capacitors is proposed to close.
CXCR3high CD8+ T cells with naïve phenotype and high capacity for IFN‐γ production are generated during homeostatic T‐cell proliferation
Authors: Kato Aiko , Takaori‐Kondo Akifumi , Minato Nagahiro , Hamazaki Yoko
Published: July 2018

Naïve phenotype (NP) T cells spontaneously initiate homeostatic proliferation (HP) as T‐cell output is reduced because of physiologic thymic involution with age. However, the effects of sustained HP on overall immune function are poorly understood. We demonstrated that the NP CD8+ T cell population in adult thymectomized mice showing accelerated HP has an increased capacity for TCR‐mediated interferon‐γ and tumor necrosis factor α production, which is attributed to an increase in CXCR3+ cells in the NP CD8+ T cell population. The CXCR3+ NP CD8+ T cells developed during persistent HP with a slow cell division rate, but rarely during robust antigen‐driven proliferation with a fast cell division rate. In ontogeny, the proportions of CXCR3+ cells in the NP CD8+ T cell population showed a biphasic profile, which was high at the newborn and aged stages. Upon transfer, CXCR3+ NP CD8+ T cells, but not CXCR3− NP CD8+ T cells, potently enhanced Th17‐mediated inflammatory tissue reactions in vivo. Furthermore, CXCR3high NP CD8+ T cells with similar features were also detected at variable levels in healthy human blood. These results suggest that CXCR3+ NP CD8+ T cells generated during physiological HP significantly impact overall immunity at the immunologically vulnerable neonatal and aged stages.
Sequencing of mitochondrial genomes using the Precision ID mtDNA Whole Genome Panel
Authors: Pereira Vania , Longobardi Antonio , Børsting Claus
Published: July 2018

Massively parallel sequencing offers a fast and cost‐effective method for sequencing of the whole mtDNA genome. The Precision ID mtDNA Whole Genome Panel amplifies the entire mtDNA genome in two multiplex PCRs with 81 primer sets using the Ion AmpliSeq™ technology. In this study, the performance of the panel was evaluated by testing different amplification methods (two‐in‐one or conservative), the number of PCR cycles (21, 23, and 25), and different reaction volumes (recommended volume or half‐volume). Furthermore, a dilution series, controlled mtDNA mixtures, and casework samples were also sequenced. The normalised read depths of the individual fragments were highly consistent irrespectively of the amplification methods or reaction volumes used. The sequencing output matched the mixture ratios of the controlled mtDNA mixtures indicating that the sequencing results were a loyal representation of the input DNA. Complete mtDNA profiles were generated from <10 pg genomic DNA. Seven fragments with relatively low read depths and large variations in read depth were identified. One of these fragments covered part of the control region and the hypervariable region II.
Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients
Authors: Boëlle Pierre‐Yves , Debray Dominique , Guillot Loic , Clement Annick , Corvol Harriet ,   on behalf of the French CF Modifier Gene Study Investigators
Published: July 2018

Cystic fibrosis (CF)–related liver disease (CFLD) is a common symptom in patients with CF. However, its prevalence, risk factors, and evolution are unclear. We analyzed a large database of patients with CF to investigate the incidence of CFLD, its related risk factors, and the use and effect of ursodeoxycholic acid (UDCA) treatment. We retrospectively analyzed 3,328 CF patients with pancreatic insufficiency born after 1985 and recruited into the French CF Modifier Gene Study since 2004. We determined liver status, age at CFLD and severe CFLD onset, sex, CFTR genotype, history of meconium ileus, treatment with UDCA, and respiratory and nutritional status. The incidence of CFLD increased by approximately 1% every year, reaching 32.2% by age 25. The incidence of severe CFLD increased only after the age of 5, reaching 10% by age 30. Risk factors for CFLD and severe CFLD were male sex, CFTR F508del homozygosity, and history of meconium ileus. Increasingly precocious initiation of UDCA treatment did not change the incidence of severe CFLD. Finally, patients with severe CFLD had worse lung function and nutritional status than other CF patients.
Conclusion:
CFLD occurs not only during childhood but also later in the lifetime of patients with CF; male sex, CFTR F508del homozygosity, and history of meconium ileus are independent risk factors for CFLD development; earlier use of UDCA over the last 20 years has not changed the incidence of severe CFLD, leading to questions about the use of this treatment in young children given its possible adverse effects.
Nutrition education in the Australian New South Wales primary school curriculum: An exploration of time allocation, translation and attitudes in a sample of teachers
Authors: de Vlieger Nienke , Riley Nicholas , Miller Andrew , Collins Clare E. , Bucher Tamara
Published: July 2018

Issue addressed

The dietary intakes of Australian children are not optimal, with few meeting recommended vegetable and fruit intake targets. Nutrition education in childhood is important for developing healthy eating patterns, with schools an ideal setting for a wide reach. The aims of this study were to examine nutrition education within the NSW primary school syllabus, explore how much time teachers spend teaching nutrition, what is taught, what materials are used, and to identify attitudes towards nutrition education.

Method

An online survey consisting of 29 closed questions (with options for comments) was specifically developed for the purpose of this study. Teachers currently teaching at a NSW primary school were eligible to participate.

Results

A total of 33 NSW primary school teachers completed the survey. Results indicate that limited time is spent on teaching nutrition with some important nutrition education components currently missed, resources perceived to be inadequate and lack of time reported as the largest barrier to teaching nutrition.

Conclusion

In order to improve the quality of nutrition education in NSW primary schools, several important topics need to be integrated into the curriculum, and time constraints of teachers should be taken into account.

So what?

Findings from the current survey will inform the development of future nutrition education programs and resources with the aim of integrating nutrition education within the primary school curriculum.
Understanding coastal wetland hydrology with a new regional‐scale, process‐based hydrological model
Authors: Zhang Yu , Li Wenhong , Sun Ge , Miao Guofang , Noormets Asko , Emanuel Ryan , King John S.
Published: July 2018

Coastal wetlands represent an ecotone between ocean and terrestrial ecosystems, providing important services, including flood mitigation, fresh water supply, erosion control, carbon sequestration, and wildlife habitat. The environmental setting of a wetland and the hydrological connectivity between a wetland and adjacent terrestrial and aquatic systems together determine wetland hydrology. Yet little is known about regional‐scale hydrological interactions among uplands, coastal wetlands, and coastal processes, such as tides, sea level rise, and saltwater intrusion, which together control the dynamics of wetland hydrology. This study presents a new regional‐scale, physically based, distributed wetland hydrological model, PIHM‐Wetland, which integrates the surface and subsurface hydrology with coastal processes and accounts for the influence of wetland inundation on energy budgets and evapotranspiration (ET). The model was validated using in situ hydro‐meteorological measurements and Moderate Resolution Imaging Spectroradiometer (MODIS) ET data for a forested and herbaceous wetland in North Carolina, USA, which confirmed that the model accurately represents the major wetland hydrological behaviours. Modelling results indicate that topographic gradient is a primary control of groundwater flow direction in adjacent uplands. However, seasonal climate patterns become the dominant control of groundwater flow at lower coastal plain and land–ocean interface. We found that coastal processes largely influence groundwater table (GWT) dynamics in the coastal zone, 300 to 800 m from the coastline in our study area. Among all the coastal processes, tides are the dominant control on GWT variation. Because of inundation, forested and herbaceous wetlands absorb an additional 6% and 10%, respectively, of shortwave radiation annually, resulting in a significant increase in ET. Inundation alters ET partitioning through canopy evaporation, transpiration, and soil evaporation, the effect of which is stronger in cool seasons than in warm seasons. The PIHM‐Wetland model provides a new tool that improves the understanding of wetland hydrological processes on a regional scale. Insights from this modelling study provide benchmarks for future research on the effects of sea level rise and climate change on coastal wetland functions and services.
Identification of potential anti‐hepatitis C virus agents targeting non structural protein 5B using computational techniques
Authors: Polamreddy Prasanthi , Vishwakarma Vinita , Saxena Puneet
Published: July 2018

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA‐dependent RNA polymerase that plays a key role in HCV replication, and, hence, NS5B is an attractive target for hepatitis C drug discovery. Hepatitis C is a chronic liver disease affecting the global population significantly. Many NS5B inhibitors targeting active site were launched in recent years, however, still there exists a pressing need for cost‐effective therapies with pan genotypic activity and therapies targeting niche HCV population with comorbities and resistant to earlier therapies. The objective of the current study is to identify potential anti‐HCV agents from FDA approved drugs that are already in the market for a different disease—Drug repurposing approach. A combination of computational chemistry and computational biology techniques was used to discover potential therapies for hepatitis C targeting the NS5B Thumb I allosteric site. Computational chemistry analysis emphasized the fact that fluvastatin, a lipid lowering agent, and olopatadine, an antihistamine, exhibited good binding affinity to NS5B. In addition, gene set enrichment analysis brought to light the significant overlap between disease characteristic features and the mechanism of action of fluvastatin and olopatadine. The current study concludes the potentially beneficial use of fluvastatin in niche hepatitis C patient population suffering from nonalcoholic fatty liver diseases.
17β‐Estradiol inhibits testosterone‐induced cell proliferation in HepG2 by modulating the relative ratios of 3 estrogen receptor isoforms to the androgen receptor
Authors: Xu Zhixiang , Liu Jun , Jianxin Cao , Yongliang Zhuang , Pan Xuejun
Published: July 2018

Sex hormones, especially 17β‐estradiol (E2) and testosterone (TEST), play crucial roles in the oncogenesis and progression of liver cancer via hormone‐related receptors. As women have a lower rate of hepatocellular carcinoma (HCC) than men, estrogens might attenuate the occurrence and development of HCC. This study aimed to investigate the inhibitory effects and mechanisms of E2 on TEST‐induced HCC development; the HepG2 cell line was used as an in vitro model. Five endpoints, including cell viability, cell apoptosis, cell cycle, receptor protein expression, and messenger RNA transcription, were investigated. Different roles and the ratios of androgen receptor (AR) and 3 estrogen receptor (ER) subtypes were also estimated. Cell viability assay showed that co‐treatment of E2 and TEST resulted in a significant inhibition of E2‐induced or TEST‐induced cell proliferation. Flow cytometry analysis revealed that combined treatment of E2 and TEST blocked the cell cycle in the G0/G1 phase as well as induced cell early apoptosis, characterized by decreased cyclin‐dependent kinase transcription and the ratio of Bcl‐2/Bax. Real‐time quantitative polymerase chain reaction and Western blot analysis results further demonstrated that estrogen receptor estrogen receptor α66 (ERα66) and estrogen receptor β (ERβ) were upregulated, whereas AR and estrogen receptor α36 (ERα36) were downregulated, irrespective of whether E2 and TEST were considered separately or together, whereas the combined treatment of E2 and TEST resulted in a decrease in the ERα66/ERβ ratio, the ERα66/ERα36 ratio, and the ERβ/ERα36 ratio, but with an increase in the ERα66/AR ratio, the ERα36/AR ratio, and the ERβ/AR ratio. To sum up, E2 could inhibit TEST‐induced cell proliferation by modulating the ratio of different hormone‐related receptors.
Benzimidazoles as novel deoxyribonuclease I inhibitors
Authors: Kolarević Ana , Ilić Budimir S. , Anastassova Neda , Mavrova Anelia Ts. , Yancheva Denitsa , Kocić Gordana , Šmelcerović Andrija
Published: July 2018

Inhibitory potential of 19 benzimidazoles against bovine pancreatic deoxyribonuclease I (DNase I) was investigated in vitro. Three compounds inhibited DNase I with IC50 below 100 μM and proved to be more potent DNase I inhibitors than crystal violet (IC50 = 351.82 ± 29.41 μM), used as a positive control. Compound 9 showed the most potent DNase I inhibition with an IC 50 value of 79.46 ± 11.75 μM. To further explore the relationship between inhibitory activity and 2D pharmacophore features, Pharma/E‐State R‐group quantitative structure‐activity relationship (RQSAR) models were generated and validated using Schrödinger Suite. RQSAR models showed a significant enhancement of benzimidazoles activity using hydrogen‐bond acceptor substituents at the R2, R3, and R4 positions, or aryl substituents at the R4 position. The Site Finder module and molecular docking defined the benzimidazoles interactions with the most important catalytic residues of DNase I, including H‐acceptor interaction with residue His 134 and His 252 and/or H‐donor interaction with residue Glu 39. We also found a positive correlation between IC50 inhibition values and relative binding free energies of the most active benzimidazoles. In addition, a molecular dynamics simulation was performed for DNase I‐compound
9 docking complex in Desmond. Trajectory analysis showed that docking complex and intermolecular interactions were stable throughout the entire production part of simulations. Furthermore, the results of protein structure alignment module suggested the potential translational impact of benzimidazoles against human DNase I. Due to the significant involvement of DNase I in the pathophysiology of many disease conditions, benzimidazoles as DNase I inhibitors could have potential therapeutic applications.
Performance evaluation of the mindray anti‐HCV assay for the detection of hepatitis C virus infection
Authors: Yue Zhi‐hong , Xia Chang‐sheng , Wang Hui
Published: July 2018

Background

Anti‐hepatitis C virus (anti‐HCV) antibody assays are recommended for HCV infection screening. The Mindray anti‐HCV assay, based on a third‐generation immunoassay, was recently launched in China. We aimed to evaluate its diagnostic performance compared with that of two other widely used assays.

Methods

Six HCV infection seroconversion panels were used to evaluate the sensitivity of the assay for early detection. A total of 1952 clinical samples were tested by the Mindray anti‐HCV, Elecsys anti‐HCV II, and Architect anti‐HCV assays. Samples with reactive results using at least one anti‐HCV assay were further tested with the recombinant immunoblot assay (RIBA). Inconsistent results were investigated by the HCV RNA assay and HCV core antigen assay. HCV infection diagnosis was made according to the results of laboratory tests and medical records.

Results

The Mindray anti‐HCV assay and Elecsys anti‐HCV II assay detected seroconversion in an average of 12.5 days and 10.5 days, respectively, and this difference was not significant (P = .818). Of the 1952 cases, 90 were categorized as “HCV infection” and 1862 were categorized as “no HCV infection.” The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR‐) of each assay were as follows: the Mindray anti‐HCV assay, 95.6%, 99.2%, 85.1%, 99.8%, 118.6 and 0.045, respectively; the Architect anti‐HCV assay, 98.9%, 95.2%, 50.0%, 99.9%, 20.69 and 0.012, respectively; and the Elecsys anti‐HCV II assay, 96.7%, 99.9%, 98.9%, 99.8%, 1799.9 and 0.033, respectively. There were significant differences in the specificity, PPV and LR+ among the three assays (P < .001). There were no significant differences in the sensitivity, NPV or LR‐ among the three assays (P > .05).

Conclusions

The Mindray anti‐HCV assay displays a similar sensitivity to the Elecsys anti‐HCV II assay with respect to the early detection of HCV infection. The Mindray anti‐HCV assay shows excellent diagnostic performance and is suitable for the screening of HCV infection.
Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay
Authors: Tange Clare E. , Kaur Amrit , Verma Nisha , Hickey Alaco , Grigoriadou Sofia , Scott Chris , Kiani Sorena , Steven Rachael , Ponsford Mark , El‐Shanawany Tariq , Jolles Stephen , Harding Stephen , Parker Antony R.
Published: July 2018

Background

Impaired levels or function of C1 inhibitor (C1‐INH) results in angioedema due to increased bradykinin. It is important to distinguish between angioedema related to C1‐INH deficiency and that caused by other mechanisms, as treatment options are different. In hereditary (HAE) and acquired (AAE) angioedema, C1‐INH concentration is measured to aid patient diagnosis. Here, we describe an automated turbidimetric assay to measure C1‐INH concentration on the Optilite® analyzer.

Methods

Linearity, precision, and interference were established over a range of C1‐INH concentrations. The 95th percentile reference interval was generated from 120 healthy adult donors. To compare the Optilite C1‐INH assay with a predicate assay used in a clinical laboratory, samples sent for C1‐INH investigation were used. The predicate results were provided to allow comparison.

Results

The Optilite C1‐INH assay was linear across the measuring range at the standard sample dilution. Intra and interassay variability was <6%. The 95th percentile adult reference interval for the assay was 0.21‐0.38 g/L. There was a strong correlation between the Optilite concentrations and those generated with the predicate assay (R2 = 0.94, P < 0.0001, slope y = 0.83x). All patients with Type I HAE (n = 24) and AAE (n = 3) tested had concentrations below the measuring range in both assays, while all patients with unspecified angioedema (UAE), not diagnosed with HAE or AAE had values within the reference range.

Conclusion

The Optilite assay allows the automated and precise quantification of C1‐INH concentrations in patient samples. It could therefore be used as a tool to aid the investigation of patients with angioedema.