bluuebunny/crossref_metadata_2025 huggingface dataset:
Disulfide‐Bridged Organosilica Frameworks: Designed, Synthesis, Redox‐Triggered Biodegradation, and Nanobiomedical Applications
Authors: Du Xin , Kleitz Freddy , Li Xiaoyu , Huang Hongwei , Zhang Xueji , Qiao Shi‐Zhang
Published: April 2018

Over the past few years, silica‐based nanotheranostics have demonstrated their great potential for nano/biomedical applications. However, the uncontrollable and difficult degradability of their pure silica framework and long‐time in vivo retention still cause severe and unpredictable toxicity risks. Therefore, it is highly desirable to design and synthesize materials with safer framework structures and compositions. To this aim, the introduction of disulfide bonds into the silica framework can not only maintain high stability in physiological conditions, but also achieve a stimuli‐responsive biodegradation triggered by intracellular reducing microenvironment in living cells, especially in cancer cells. Once nanotheranostics with disulfide (i.e., thioether)‐bridged silsesquioxane framework are taken up by tumor cells via passive or active targeting, the disulfide bonds in the hybrid silica matrix can be cleaved by a high concentration of intracellular glutathione, enabling redox‐triggered biodegradation of the nanosystems for both concomitant release of the loaded therapeutic cargo and in vivo clearance. It is envisioned that such hybrid materials comprised of disulfide‐bridged silsesquioxane frameworks can become promising responsive and biodegradable nanotheranostics. This review summarizes the recent advances in the synthesis of hybrid organosilicas with disulfide‐bridged silsesquioxane frameworks, and discuss their redox‐triggered biodegradation behaviors combined with their biocompatibility and nanobiomedical applications.
In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease
Authors: Khodabukus Alastair , Prabhu Neel , Wang Jason , Bursac Nenad
Published: April 2018

Healthy skeletal muscle possesses the extraordinary ability to regenerate in response to small‐scale injuries; however, this self‐repair capacity becomes overwhelmed with aging, genetic myopathies, and large muscle loss. The failure of small animal models to accurately replicate human muscle disease, injury and to predict clinically‐relevant drug responses has driven the development of high fidelity in vitro skeletal muscle models. Herein, the progress made and challenges ahead in engineering biomimetic human skeletal muscle tissues that can recapitulate muscle development, genetic diseases, regeneration, and drug response is discussed. Bioengineering approaches used to improve engineered muscle structure and function as well as the functionality of satellite cells to allow modeling muscle regeneration in vitro are also highlighted. Next, a historical overview on the generation of skeletal muscle cells and tissues from human pluripotent stem cells, and a discussion on the potential of these approaches to model and treat genetic diseases such as Duchenne muscular dystrophy, is provided. Finally, the need to integrate multiorgan microphysiological systems to generate improved drug discovery technologies with the potential to complement or supersede current preclinical animal models of muscle disease is described.
38th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2017 Annual Meeting
Authors: Stevens Cathy A. , Krantz Ian
Published: April 2018

The 38th Annual David W. Smith Workshop on Malformations and Morphogenesis occurred on August 26th – 29th, 2017 at the Stoweflake Resort and Conference Center in Stowe, VT. The Workshop, which honors the legacy of David W Smith, brought together clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. The Workshop highlighted four themes besides mechanisms of morphogenesis and new syndromes: Disorders of Transcriptional Regulation, Dysmorphology (Syndromes and Malformations) in Minority and Unique Populations, Syndromes and Isolated Birth Defects Involving Malformations of the Developing Foregut, and the Natural History of Syndromes. This Conference Report includes the abstracts presented at the 2017 Workshop.
Delayed peak response of cortisol to insulin tolerance test in patients with Prader–Willi syndrome
Authors: Oto Yuji , Matsubara Keiko , Ayabe Tadayuki , Shiraishi Masahisa , Murakami Nobuyuki , Ihara Hiroshi , Matsubara Tomoyo , Nagai Toshiro
Published: April 2018

Deaths among children with Prader–Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus‐pituitary‐adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5–3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age‐matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3–27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2–23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3–48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5–22.0 pg/ml), 15.6 (IQR, 11.9–21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7–30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis.
Robust Preparation of Atomic Concatenated Greenberger–Horne–Zeilinger States via Shortcuts to Adiabaticity
Authors: Lin Jin‐Zhong
Published: April 2018

Here, a protocol for robust preparation of an atomic concatenated Greenberger–Horne–Zeilinger (C‐GHZ) state via shortcuts to adiabaticity (STA) is proposed. The devices for implementing the protocol consist of atoms, cavities, and the optical fibers, which are feasible with current technology. The atoms are trapped in the separated cavities allowing individual control over each atom with classical fields. STA helps to design Rabi frequencies of classical fields so that the atoms can be driven from the initial states to the target states. The numerical simulations show that the protocol holds robustness against atomic spontaneous emissions and photonic leakages. Thus, the protocol may be realized by experiments in the near future.
Intermolecular Arrangement of Fullerene Acceptors Proximal to Semiconducting Polymers in Mixed Bulk Heterojunctions
Authors: Wang Chao , Nakano Kyohei , Lee Hsiao Fang , Chen Yujiao , Hong You‐Lee , Nishiyama Yusuke , Tajima Keisuke
Published: April 2018

Precise control of the molecular arrangements at the interface between the electron donor and acceptor in mixed bulk heterojunctions (BHJs) remains challenging, despite the correlation between structural characteristics and efficiency in organic photovoltaics (OPVs). This study reveals that the substitution patterns of linear and branched alkyl side chains on electron‐donating/‐accepting alternating copolymers can control the positions of an acceptor molecule (C60) around the π‐conjugated main chains in mixed BHJs. Two‐dimensional solid‐state NMR demonstrates a marked difference in the location of C60 in the blend films. A copolymer with an electron‐accepting unit positioned in close proximity to C60 demonstrated higher OPV performance in combination with various fullerene derivatives. This molecular design offers precise control over the interfacial molecular structure, thereby paving the way for overcoming the current limitations of OPVs comprising mixed BHJs.
Water‐Binding‐Mediated Gelation/Crystallization and Thermosensitive Superchirality
Authors: Xing Pengyao , Li Yongxin , Wang Yang , Li Pei‐Zhou , Chen Hongzhong , Phua Soo Zeng Fiona , Zhao Yanli
Published: April 2018

Determination of molecular structural parameters of hydrophobic cholesterol–naphthalimide conjugates for water binding capabilities as well as their moisture‐sensitive supramolecular self‐assembly were revealed. Water binding was a key factor in leading trace water‐induced crystallization against gelation in apolar solvent. Ordered water molecules entrapped in self‐assembly arrays revealed by crystal structures behave as hydrogen‐bonding linkers to facilitate three‐dimensional growth into crystals rather than one‐dimensional gel nanofibers. Water binding was also reflected on the supramolecular chirality inversion of vesicle self‐assembly in aqueous media via heating‐induced dehydration. Structural parameters that favor water binding were evaluated in detail, which could help rationally design organic building units for advancing soft materials, crystal engineering, and chiral recognition.
Janus Graft Block Copolymers: Design of a Polymer Architecture for Independently Tuned Nanostructures and Polymer Properties
Authors: Guo Zi‐Hao , Le An N. , Feng Xunda , Choo Youngwoo , Liu Bingqian , Wang Danyu , Wan Zhengyi , Gu Yuwei , Zhao Julia , Li Vince , Osuji Chinedum O. , Johnson Jeremiah A. , Zhong Mingjiang
Published: April 2018

The graft‐through synthesis of Janus graft block copolymers (GBCPs) from branched macromonomers composed of various combinations of homopolymers is presented. Self‐assembly of GBCPs resulted in ordered nanostructures with ultra‐small domain sizes down to 2.8 nm (half‐pitch). The grafted architecture introduces an additional parameter, the backbone length, which enables control over the thermomechanical properties and processability of the GBCPs independently of their self‐assembled nanostructures. The simple synthetic route to GBCPs and the possibility of using a variety of polymer combinations contribute to the universality of this technique.
Simultaneous Quantification of Multiple Cancer Biomarkers in Blood Samples through DNA‐Assisted Nanopore Sensing
Authors: Liu Lei , Li Ting , Zhang Shouwen , Song Peng , Guo Bingyuan , Zhao Yuliang , Wu Hai‐Chen
Published: April 2018

Protein biomarkers in blood have been widely used in the early diagnosis of disease. However, simultaneous detection of many biomarkers in a single sample remains challenging. Herein, we show that the combination of a sandwich assay and DNA‐assisted nanopore sensing could unambiguously identify and quantify several antigens in a mixture. We use five barcode DNAs to label different gold nanoparticles that can selectively bind specific antigens. After the completion of the sandwich assay, barcode DNAs are released and subject to nanopore translocation tests. The distinct current signatures generated by each barcode DNA allow simultaneous quantification of biomarkers at picomolar level in clinical samples. This approach would be very useful for accurate and multiplexed quantification of cancer‐associated biomarkers within a very small sample volume, which is critical for non‐invasive early diagnosis of cancer.
Surface Engineering of Carbon Nitride Electrode by Molecular Cobalt Species and Their Photoelectrochemical Application
Authors: Chen Zupeng , Wang Hongqiang , Xu Jingsan , Liu Jian
Published: April 2018

Graphitic carbon nitride (CN) has been widely regarded as a promising photocatalyst since the discovery of its capability for photocatalytic hydrogen evolution. Herein, we developed a functional CN film on a conductive fluorine‐doped tin oxide (FTO) electrode by using a microprinting‐based direct growth method. Furthermore, the photoelectrochemical performance of the derived CN@FTO film was demonstrated to be enhanced by incorporating molecular cobalt species. The reduced charge transport resistance in the cobalt‐modified CN@FTO films is suggested to accelerate the charge‐carrier transfer rate and thus to improve the performance in photoelectrochemical application. The approach is versatile and can be further optimized by selecting a proper “ink” solution and modifier on various conductive substrates.
Visible‐Light‐Promoted Synthesis of Fluoroalkylated Oximes
Authors: Lee Da Seul , Hwang Ho Seong , Cho Eun Jin
Published: April 2018

A method has been developed for the synthesis of fluoroalkylated oximes, potential fluoroalkyl building‐blocks for the synthesis of various organofluorine compounds, from easily available amino substrates and fluoroalkylated alkenes. tBuONO was utilized both as a diazotizing agent and as a NO radical source for the oxime synthesis in the process, and the use of a photocatalyst under visible‐light irradiation increased the efficiency of the reaction. Various fluoroalkylated oximes were prepared by a tandem process of aryl radical addition to fluoroalkylated alkene and consecutive oxime generation process, albeit in moderate yields. This differentiated approach, transferring an aromatic system into an electron‐deficient fluoroalkylated alkene, expands the scope of substrates where electron‐poor aromatic systems could be utilized.
Solventless Catalytic Etherification of Glycerol Using Acetate Salts as Efficient Catalysts
Authors: Lee Ji Hyun , Park Seo Kyoung , Ryu Jung‐Bok , Lee Hyunjoo , Lee Je Seung
Published: April 2018

Diglycerol (DG) and triglycerol (TG) were synthesized via dehydrative etherification reaction of glycerol without solvent. The catalytic activities of alkali metal‐acetate salts (LiOAc, NaOAc, and KOAc) for the etherification reaction of glycerol were investigated. Compared to the stronger basic catalysts, the less basic catalysts showed higher selectivity of DG and TG. A half mol % of LiOAc exhibited excellent selectivities of DG and TG as 52.5 and 30.4%, at 260 °C and 6 h. The dependence of reaction on the relative basicity and loading amount of catalyst, reaction time, and reaction temperature were investigated to elucidate the characteristics of etherification reaction of glycerol.
Applications of virtual reality in learning the photoelectric effect of liquid crystal display
Authors: Tarng Wernhuar , Lee Chi‐Young , Lin Chih‐Ming , Chen Wei‐Hun
Published: April 2018

Liquid crystals are the matter in a state with properties between solid crystals and conventional liquids. Due to their special physical, chemical, and photoelectric properties, liquid crystals are often applied in the displays of portable consumer devices because they can solve the problems of heavy weights and large sizes in traditional cathode ray tube (CRT) displays. Virtual reality (VR) is a computer technology to create an immersive environment for simulating the real world through one's sense organs. The user can see and hear as if situated in the real world, and even interact with virtual objects or other people manifested by avatars to experience lifelike feelings in the virtual environments. In this study, a virtual laboratory is developed for learning the photoelectric effect of liquid crystal displays (LCD). The users can operate the LCD device by changing the electric field to control the direction of crystal alignment. They can also manipulate a marquee on the LCD to move the text from the left (or right) to the opposite direction, and use LCD shuttle glasses to view stereo images to understand its operating principle. A teaching experiment has been conducted to investigate the learning effectiveness of the virtual laboratory in comparison with that of using traditional teaching aids. The results show that the virtual laboratory could enhance students' learning interest and achievement. They believed that the high interactivity and 3D visualization could help them understand the photoelectric effect of LCD.
The prognostic impact of revascularization strategy in acute myocardial infarction and cardiogenic shock: Insights from the British Columbia Cardiac Registry
Authors: McNeice Andrew , Nadra Imad J. , Robinson Simon D. , Fretz Eric , Ding Lillian , Fung Anthony , Aymong Eve , Chan Albert W. , Hodge Steven , Webb John , Sheth Tej , Jolly Sanjit S. , Mehta Shamir R. , Della Siega Anthony , Wood David A. , Iqbal M. Bilal ,   on behalf of the British Columbia Cardiac Registry Investigators
Published: April 2018

Background

In patients with acute myocardial infarction (AMI) and cardiogenic shock (CS), percutaneous coronary intervention (PCI) of the culprit vessel is associated with improved outcomes. A large majority of these patients have multivessel disease (MVD). Whether or not PCI of non‐culprit disease in the acute setting improves outcomes continues to be debated. We evaluated the prognostic impact of revascularization strategy for patients presenting with AMI and CS.

Methods

We compared culprit vessel intervention (CVI) versus multivessel intervention in 649 patients with AMI, CS, and MVD enrolled in the British Columbia Cardiac Registry. We evaluated mortality at 30 days and 1 year.

Results

CVI was associated with lower mortality at 30 days (23.7% vs. 34.5%, P = 0.004) and 1 year (32.6% vs. 44.3%, P = 0.003). CVI was an independent predictor for survival at 30 days (HR = 0.63, 95% CI: 0.45–0.88, P = 0.009) and 1 year (HR = 0.72, 95% CI: 0.54–0.96, P = 0.027). These findings were confirmed in propensity‐matched cohorts. Subgroup analyses indicated that CVI was associated with lower mortality in patients aged <80 years; non‐diabetics; and those presenting with ST‐elevation MI. When analyzing non‐culprit anatomy, PCI of non‐culprit LAD disease was associated with higher 1‐year mortality (HR = 1.51, 95% CI: 1.13–2.01, P = 0.006), primarily with non‐culprit proximal LAD disease (HR = 1.82, 95% CI: 1.20–2.76, P = 0.005). However, PCI of non‐culprit non‐proximal LAD, LCx, and RCA disease was not associated with mortality.

Conclusions

In patients with AMI and CS, a strategy of CVI appears to be associated with lower mortality. These findings are consistent with recently published randomized‐controlled trial data.
Improved Electrocatalytic Performance in Overall Water Splitting with Rational Design of Hierarchical Co3O4@NiFe Layered Double Hydroxide Core–Shell Nanostructure
Authors: Wang Shanpeng , Wu Jian , Yin Junwen , Hu Qi , Geng Dongsheng , Liu Li‐Min
Published: April 2018

The front cover artwork is provided by the groups of Li‐Min Liu (Beijing Computational Science Research Center, China) and Dongsheng Geng (University of Science and Technology Beijing, China). The cover picture shows that the as‐prepared Co3O4@NiFe layered double hydroxide electrode with a core–shell structure exhibits excellent electrocatalyst performance in overall water splitting. Read the full text of the Article at 10.1002/celc.201800194.
C‐Functionalized Cationic Diazaoxatriangulenes: Late‐Stage Synthesis and Tuning of Physicochemical Properties
Authors: Delgado Irene Hernández , Pascal Simon , Besnard Céline , Voci Silvia , Bouffier Laurent , Sojic Neso , Lacour Jérôme
Published: April 2018

A series of nine C‐functionalized cationic diazaoxatriangulene (DAOTA) dyes have been successfully synthesized and fully characterized, including X‐ray structural analysis of four derivatives. The introduction of electron‐withdrawing or ‐donating functions enables the tuning of both electro‐ and photochemical properties with, for instance, two consecutive (reversible) reductions or oxidations observed for nitro or amino derivatives, respectively. The substituents also impacted on the optical properties, with absorption maxima varying from λ=528 to 640 nm and fluorescence being shifted from the yellow to the red range, up to λ=656 nm.
Donor‐influenced Structure–Activity Correlations in Stoichiometric and Catalytic Reactions of Lithium Monoamido‐Monohydrido‐Dialkylaluminates
Authors: Lemmerz Lara E. , McLellan Ross , Judge Neil R. , Kennedy Alan R. , Orr Samantha A. , Uzelac Marina , Hevia Eva , Robertson Stuart D. , Okuda Jun , Mulvey Robert E.
Published: April 2018

A series of heteroleptic monoamido‐monohydrido‐dialkylaluminate complexes of general formula [iBu2AlTMPHLi⋅donor] were synthesized and characterised in solution and in the solid state. Applying these complexes in catalytic hydroboration reactions with representative aldehydes and ketones reveals that all are competent, however a definite donor substituent effect is discernible. The bifunctional nature of the complexes is also probed by assessing their performance in metallation of a triazole and phenylacetylene and addition across pyrazine. These results lead to an example of phenylacetylene hydroboration, which likely proceeds via deprotonation, rather than insertion as observed with the aldehydes and ketones. Collectively, the results emphasise that reactivity is strongly influenced by both the mixed‐metal constitution and mixed‐ligand constitution of the new aluminates.
A cationic polymer enhanced PAC for the removal of dissolved aquatic organic carbon and organic nitrogen from surface waters
Authors: Wang Chuang , Zhu Guocheng , Ren Bozhi , Zhang Peng , Hursthouse Andrew
Published: April 2018

Dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) are important components of the aquatic environment and may produce harmful disinfection by‐products through chlorination associated with water treatment processes. Therefore, it is necessary to remove them from the water. Coagulation is a cost‐effective water treatment technique as the key unit in the pretreatment of drinking water but deals with DON poorly. We present a study to investigate the enhancement of poly aluminum chloride (PAC) using a cationic polymer for the removal of both DON and DOC. The cationic dimethyl diallyl ammonium chloride (PDMDAAC) polymer was hybridized with PAC to remove DON and DOC. The results showed that the PDMDAAC increased the charge neutralization capacity of PAC and floc aggregation, thereby increasing the settling efficiency of the flocs. The PDMDAAC increased the amount of colloidal species in PAC, which was beneficial to the formation of adsorption‐bridging. With the increase of pH, a greater proportion of colloidal adsorption sites were used in the removal of DON. The DOC, DON, and turbidity removal were dependent on multiple interactions through charge neutralization, adsorption‐bridging, and floc sweeping. However, DOC and DON removal were primarily determined by adsorption‐bridging and floc sweeping, while turbidity removal was mainly dependent on charge neutralization.
Droplet Digital PCR with EvaGreen Assay: Confirmational Analysis of Structural Variants
Authors: Tai Angela C. , Parfenov Michael , Gorham Joshua M.
Published: April 2018

DNA structural variants can be analyzed by droplet digital PCR (ddPCR), a water‐oil microfluidics and fluorescence technology to quantify target nucleic acids with extreme precision and sensitivity. Traditional ddPCR uses expensive fluorescent oligonucleotide probes that require extensive optimization. Here we describe a variation of ddPCR using a DNA‐binding dye (EvaGreen), whose properties allow target products to be effectively quantified at a significantly lower cost. © 2018 by John Wiley & Sons, Inc.
Overview of Huntington's Disease Models: Neuropathological, Molecular, and Behavioral Differences
Authors: Rangel‐Barajas Claudia , Rebec George V.
Published: April 2018

Transgenic mouse models of Huntington's disease (HD), a neurodegenerative condition caused by a single gene mutation, have been transformative in their ability to reveal the molecular processes and pathophysiological mechanisms underlying the HD behavioral phenotype. Three model categories have been generated depending on the genetic context in which the mutation is expressed: truncated, full‐length, and knock‐in. No single model, however, broadly replicates the behavioral symptoms and massive neuronal loss that occur in human patients. The disparity between model and patient requires careful consideration of what each model has to offer when testing potential treatments. Although the translation of animal data to the clinic has been limited, each model can make unique contributions toward an improved understanding of the neurobehavioral underpinnings of HD. Thus, conclusions based on data obtained from more than one model are likely to have the most success in the search for new treatment targets. © 2018 by John Wiley & Sons, Inc.
An updated overview with simple and practical approach for developing in vitro–in vivo correlation
Authors: Jacob Shery , Nair Anroop B
Published: April 2018

Preclinical Research & Development

An in vitro–in vivo correlation (IVIVC) is as a predictive mathematical model that demonstrates a key role in the development, advancement, evaluation and optimization of extended release, modified release and immediate release pharmaceutical formulations. A validated IVIVC model can serve as a surrogate for bioequivalence studies and subsequently save time, effort and expenditure during pharmaceutical product development. This review discusses about different levels of correlations, general approaches to develop an IVIVC by mathematical modelling, validation, data analysis and various applications. In the current setting, the dearth of success associated with IVIVC is due to complexity of underlying scientific principles as well as the practice of fitting/matching in vivo plasma level‐time data with in vitro dissolution profile. Hence, a simple, straightforward practical means to predict plasma drug levels by convolution technique and percentage drug absorbed computed from in vitro dissolution profile based on deconvolution method are illustrated. The bioavailability/bioequivalence assessment and evaluation are frequently validated by the pharmacokinetic parameters such as maximum concentration, time to reach maximum concentration, and area under the curve. The implementation of a quality by design manufacturing based on in vivo bioavailability and clinically relevant dissolution specification are recommended because corresponding design safe space will guarantee that all batches from relevant products are met with sufficient quality and bioperformance. Recently, United States Food and Drug Administration and European Medicines Agency have proposed that in silico/physiologically based pharmacokinetic modelling can be used in decision making during preclinical experiments as well as to recognize the dissolution profiles that can forecast and ensure the desired clinical performance.
Reduced embryonic blood flow impacts extracellular matrix deposition in the maturing aorta
Authors: Espinosa M. Gabriela , Taber Larry A. , Wagenseil Jessica E.
Published: April 2018

Background: Perturbations to embryonic hemodynamics are known to adversely affect cardiovascular development. Vitelline vein ligation (VVL) is a model of reduced placental blood flow used to induce cardiac defects in early chick embryo development. The effect of these hemodynamic interventions on maturing elastic arteries is largely unknown. We hypothesize that hemodynamic changes impact maturation of the dorsal aorta (DA). Results: We examined the effects of VVL on hemodynamic properties well into the maturation process and the corresponding changes in aortic dimensions, wall composition, and gene expression. In chick embryos, we found that DA blood velocity was reduced immediately postsurgery at Hamburger‐Hamilton (HH) stage 18 and later at HH36, but not in the interim. Throughout this period, DA diameter adapted to maintain a constant shear stress. At HH36, we found that VVL DAs showed a substantial decrease in elastin and a modest increase in collagen protein content. In VVL DAs, up‐regulation of elastic fiber–related genes followed the down‐regulation of flow‐dependent genes. Together, these suggest the existence of a compensatory mechanism in response to shear‐induced delays in maturation. Conclusions: The DA's response to hemodynamic perturbations invokes coupled mechanisms for shear regulation and matrix maturation, potentially impacting the course of vascular development. Developmental Dynamics 247:914–923, 2018. © 2018 Wiley Periodicals, Inc.
“Normal” Creatinine Levels Predict Persistent Kidney Injury and Waitlist Mortality in Outpatients With Cirrhosis
Authors: Cullaro Giuseppe , Park Meyeon , Lai Jennifer C.
Published: April 2018

Acute kidney injury (AKI) is a critical determinant of outcomes in hospitalized patients with cirrhosis, but little is known of the impact of AKI in the outpatient setting. We analyzed 385 adult outpatients with cirrhosis listed for liver transplant at a single center; excluded were those with severe hepatic encephalopathy, with hepatocellular carcinoma, or on hemodialysis. Baseline serum creatinine (bCr) was defined as the lowest value recorded, peak Cr as the highest value, ΔCr as peak Cr minus bCr, AKI as a rise in serum Cr (sCr) by ≥0.3 mg/dL from bCr, persistent kidney injury as elevation of sCR by ≥0.3 mg/dL from bCr on each subsequent clinical assessment. Among 385 outpatients with cirrhosis, bCr was ≤0.70, 0.70‐0.97, and ≥0.97 mg/dL in 28%, 38%, and 34%, respectively. At a median follow‐up of 16 (range 8‐28) months, 143 (37%) had one or more AKI episode, which increased significantly by bCr group (24% versus 37% versus 48%, P = 0.001). Of these 143 with AKI, 13% developed persistent kidney injury. A multivariable Cox regression analysis highlighted that bCr (hazard ratio [HR], 2.96) and ΔCr (HR, 2.05) were the only factors independently associated with the development of persistent kidney injury (P < 0.001). The likelihood of death/delisting increased by bCr group (14% versus 19% versus 28%, P = 0.03). A competing risk analysis demonstrated that each 1 mg/dL increase in bCr was independently associated with a 62% higher risk of death/delisting when accounting for transplantation and adjusting for confounders. Conclusion: AKI is not only common in outpatients with cirrhosis but even “clinically normal” bCr levels significantly impact the risk of persistent kidney injury and waitlist mortality, supporting the need for a lower clinical threshold to initiate monitoring of renal function and implementation of kidney‐protective strategies.
Preemptive Activation of the Integrated Stress Response Protects Mice From Diet‐Induced Obesity and Insulin Resistance by Fibroblast Growth Factor 21 Induction
Authors: Xu Xu , Krumm Christopher , So Jae‐Seon , Bare Curtis J. , Holman Corey , Gromada Jesper , Cohen David E. , Lee Ann‐Hwee
Published: April 2018

Integrated stress response (ISR) is a signaling system in which phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by stress‐specific kinases and subsequent activation of activation transcription factor (ATF) 4 help restore cellular homeostasis following exposure to environmental stresses. ISR activation has been observed in metabolic diseases, including hepatic steatosis (HS), steatohepatitis (SH), and insulin resistance (IR), but it remains unclear whether ISR contributes to disease pathogenesis or represents an innate defense mechanism against metabolic stresses. Constitutive repressor of eIF2α phosphorylation (CReP) is a critical regulatory subunit of the eIF2α phosphatase complex. Here, we show that CReP ablation causes constitutive eIF2α phosphorylation in the liver, which leads to activation of the ATF4 transcriptional program including increased fibroblast growth factor 21 (FGF21) production. Liver‐specific CReP knockout (CRePLKO) mice exhibited marked browning of white adipose tissue (WAT) and increased energy expenditure and insulin sensitivity in an FGF21‐dependent manner. Furthermore, CRePLKO mice were protected from high‐fat diet (HFD)‐induced obesity, HS, and IR. Acute CReP ablation in liver of HFD‐induced obese mice also reduced adiposity and improved glucose homeostasis. Conclusion: These data suggest that CReP abundance is a critical determinant for eIF2α phosphorylation and ensuing ISR activation in the liver. Constitutive ISR activation in the liver induces FGF21 and confers protection from HFD‐induced adiposity, IR, and HS in mice. Augmenting hepatic ISR may represent a therapeutic approach to treat metabolic disorders.
Interleukin 2 Promotes Hepatic Regulatory T Cell Responses and Protects From Biliary Fibrosis in Murine Sclerosing Cholangitis
Authors: Taylor Amy E. , Carey Alexandra N. , Kudira Ramesh , Lages Celine S. , Shi Tiffany , Lam Simon , Karns Rebekah , Simmons Julia , Shanmukhappa Kumar , Almanan Maha , Chougnet Claire A. , Miethke Alexander G.
Published: April 2018

In the multidrug resistance protein 2 (Mdr2)‐/‐ mouse model, low phospholipid bile instigates biliary epithelial injury, sterile inflammation, and fibrosis, thereby recapitulating disease mechanisms implicated in biliary atresia (BA) and primary sclerosing cholangitis. We hypothesize that T lymphocytes contribute to the biliary injury and fibrosis in murine sclerosing cholangitis (SC) and that they are susceptible to suppression by regulatory T cells (Tregs). In juvenile Mdr2‐/‐ mice, intrahepatic CD8+ lymphocytes were expanded, and contraction of intrahepatic Tregs coincided with rising serum alanine transferase and alkaline phosphatase (ALP) levels between days 14‐30 of life. Antibody‐mediated depletion of intrahepatic CD8+ lymphocytes during that time reduced ALP levels and the expression of osteopontin (Opn), a pro‐fibrogenic cytokine. Depletion of intrahepatic Tregs with anti‐CD25 antibody between days 7‐30 increased intrahepatic CD8+ T cells, Opn expression, and fibrosis. Conversely, expansion of intrahepatic Tregs with interleukin 2/anti‐interleukin 2 immune complexes (IL‐2c) downregulated hepatic expression of Opn and Tnf, reduced frequency of intrahepatic CD8+ lymphocytes, and diminished biliary injury and fibrosis. Treatment with IL‐2c upregulated hepatic Treg expression of CD39, an ectonucleotidase capable of hydrolyzing pro‐inflammatory adenosine triphosphate. In vitro, Tregs expressing CD39 suppressed the proliferation of hepatic CD8+ lymphocytes from Mdr2‐/‐ mice more efficiently than those lacking CD39. In infants with BA, infiltration of interlobular bile ducts with CD8+ cells was associated with biliary expression of Opn and its transcription was negatively correlated with mRNA expression of Treg‐associated genes. Conclusion: Hepatic CD8+ T lymphocytes drive biliary injury and fibrosis in murine SC. Their proliferation is controlled by hepatic Tregs through the purinergic pathway, which is responsive to IL‐2c, suggesting that Treg‐directed low‐dose Il‐2 treatment may be considered as therapy for SC.
Surgical simulation and applicant perception in otolaryngology residency interviews
Authors: Masood Maheer M. , Stephenson Elizabeth D. , Farquhar Douglas R. , Farzal Zainab , Shah Parth V. , Buckmire Robert A. , McClain Wade G. , Clark J. Madison , Thorp Brian D. , Kimple Adam J. , Ebert Charles S. , Kilpatrick Lauren A. , Patel Samip N. , Shah Rupali N. , Zanation Adam M.
Published: April 2018

Objective

The traditional resident applicant interview involves multiple oral interviews. The implementation of surgical simulations adds an additional dimension of assessment but can be perceived in a stressful way by applicants. The purpose of this project is to describe low‐fidelity simulations that were implemented for the 2016 to 2017 residency interviews and obtain applicant perception of these simulations.

Methods

Six simulation modules were created, which reflected tasks used in six subspecialties within otolaryngology (pediatrics, otology, laryngology, facial plastics, rhinology, and head/neck). Applicants were guided in the procedures by both an attending and resident. Afterward, applicants were anonymously surveyed on their perception of the tasks using a 5‐point Likert scale (1 = Strongly Disagree, 2 = Somewhat Disagree, 3 = Neutral, 4 = Somewhat Agree, 5 = Strongly Agree).

Results

A total of 41 applicants were interviewed. The following were measured: enjoyable (98.5% strongly agree, 2.5% somewhat agree; mean: 4.97; 95% confidence interval [CI], 4.92, 5.02), educational (88% strongly agree, 12% somewhat agree; mean: 4.88; 95% CI, 4.78, 4.98), recommended for future use (92.7% strongly agree, 7.3% somewhat agree; mean: 4.93; 95% CI, 4.85, 5.01), and stressful (63.5% strongly disagree, 19.5% somewhat disagree, 17% neutral; mean: 1.54; 95% CI, 1.30, 1.78).

Conclusion

Implementation of a low‐fidelity multi‐station surgical simulation experience is feasible in an interview day. Majority of applicants viewed the simulations in a positive manner. Surgical simulations may provide a useful holistic evaluation of an applicant in future interviews, especially if done in a setting that minimizes stress and maximizes the educational experience.

Level of Evidence

2b. Laryngoscope, 2503–2507, 2018
Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study
Authors: Butt Zeeshan , DiMartini Andrea F. , Liu Qian , Simpson Mary Ann , Smith Abigail R. , Zee Jarcy , Gillespie Brenda W. , Holtzman Susan , Ladner Daniela , Olthoff Kim , Fisher Robert A. , Hafliger Silvia , Freise Chris E. , Mandell Mercedes Susan , Sherker Averell H. , Dew Mary Amanda
Published: April 2018

Little is known about living liver donors' perceptions of their physical well‐being following the procedure. We collected data on donor fatigue, pain, and other relevant physical outcomes as part of the prospective, multicenter Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study consortium. A total of 271 (91%) of 297 eligible donors were interviewed at least once before donation and 3, 6, 12, and 24 months after donation using validated measures when available. Repeated measures regression models were used to identify potential predictors of worse physical outcomes. We found that donors reported more fatigue immediately after surgery that improved by 2 years after donation, but not to predonation levels. A similar pattern was seen across a number of other physical outcomes. Abdominal or back pain and interference from their pain were rated relatively low on average at all study points. However, 21% of donors did report clinically significant pain at some point during postdonation study follow‐up. Across multiple outcomes, female donors, donors whose recipients died, donors with longer hospital stays after surgery, and those whose families discouraged donation were at risk for worse physical well‐being outcomes. In conclusion, although not readily modifiable, we have identified risk factors that may help identify donors at risk for worse physical outcomes for targeted intervention. Liver Transplantation 00 000–000 2018 AASLD.
Customer satisfaction, Confucian dynamism, and long‐term oriented marketing relationship: A threefold empirical analysis
Authors: Ndubisi Nelson Oly , Nataraajan Rajan
Published: April 2018

Firms and their customers enter into a relationship for mutual satisfaction. However, there is much more to learn about long‐term oriented marketing relationship dynamics in Asia that lead to customer satisfaction. The goal of this study is to examine the direct and indirect effects of relational dynamics on customer satisfaction in the Asian context. Specifically, the study proposes that long‐term oriented relationship variables such as fairness, empathy, and trust have significant direct impact on customer satisfaction, and indirectly through overall relationship quality. Three studies were conducted in three service sectors viz. banking, healthcare, and hospitality with data collected from two regions of Malaysia, the Peninsular region and the Borneo region. A total of 1945 usable responses were received across the three sectors and analyzed: banking (653), healthcare (666), and hospitality (626). The model was compared among the three sectors. The results show that long‐term oriented marketing relationship variables predict a significant amount of variance in customer satisfaction across the three service sectors. However, the predictive powers differ from industry to industry, wherein 72% unique variance was predicted in the banking sector, 66% in healthcare, and 68% in hospitality. Relationship quality fully mediates some of the relationships in some sectors and partially mediates in others. Since Malaysia is dubbed a potpourri of Asian cultures, there is a potential for generalizability of the research findings across other Asian contexts. Theoretical, contextual, and managerial implications of the findings are discussed.
Assessing Angler Effort, Catch, and Harvest on a Spatially Complex, Multi-Lake Fishery in Middle Georgia
Authors: Roop Hunter J. , Poudyal Neelam C. , Jennings Cecil A.
Published: April 2018

Creel surveys are valuable tools in recreational fisheries management. However, multiple-impoundment fisheries of complex spatial structure can complicate survey designs and pose logistical challenges for management agencies. The Marben Public Fishing Area (PFA) in Mansfield, Georgia, is a multi-impoundment fishery with many access points, and these features prevent or complicate use of traditional on-site contact methods, such as standard roving or access-point designs, because many anglers may be missed during the survey process. Therefore, adaptation of a traditional survey method is often required for sampling this special case of multi-lake fisheries to develop an accurate fishery profile. Accordingly, a modified nonuniform probability roving creel survey was conducted at the Marben PFA during 2013 to estimate fishery characteristics relating to fishing effort, catch, and fish harvest. Monthly fishing effort averaged 7,523 angler-hours (SD = 5,956) and ranged from 1,301 angler-hours (SD = 562) in December to 21,856 angler-hours (SD = 5,909) in May. A generalized linear mixed model was used to determine that angler catch and harvest rates were significantly higher in the spring and summer than in the other seasons but did not vary by fishing location. Our results demonstrate the utility of modifying existing creel methodology for monitoring small, spatially complex, intensely managed impoundments that support quality recreational fisheries; these results also provide a template for the assessment and management of similar regional fisheries.
Clinical Implications of UCP1 mRNA Expression in Human Cervical Adipose Tissue Under Physiological Conditions
Authors: Lee Ju Hee , Kim Ji Min , Choi Min Jeong , Kang Yea Eun , Joung Kyoung Hye , Yi Hyon‐Seung , Kim Koon Soon , Ku Bon Jeong , Koo Bon Seok , Shong Minho , Kim Hyun Jin
Published: April 2018

Objective

The clinical implications of human brown adipose tissue (BAT) were investigated based on the analysis of cervical adipose tissue gene expression under normal physiological conditions.

Methods

Matched‐pair specimens of adipose tissue (AT) were collected from beneath the incision plane (subcutaneous AT) and from the area surrounding the carotid sheath (carotid AT) from 60 patients undergoing thyroidectomy. The mRNA expression of BAT‐associated genes in these tissues was examined, and this expression was correlated with the clinical characteristics of the subjects.

Results

The UCP1 mRNA level was significantly higher in the carotid AT than in the subcutaneous AT. There was an inverse correlation between subject age and the ratio of UCP1 mRNA expression in the carotid AT relative to the subcutaneous AT, which is a measure of BAT activity (r = −0.459; P = 0.004), and there was a negative correlation between BMI and the ratio of UCP1 mRNA expression in subjects with higher BAT activity (r = −0.532; P = 0.016).

Conclusions

UCP1 was identified as the only marker of cervical BAT in humans. There was a negative correlation between obesity and BAT activity in subjects with higher BAT activity, although BAT activity decreased with age.
Treatment of retinoblastoma in Sub‐Saharan Africa: Experience of the paediatric oncology unit at Gabriel Toure Teaching Hospital and the Institute of African Tropical Ophthalmology, Bamako, Mali
Authors: Traoré Fousseyni , Sylla Fatou , Togo Boubacar , Kamaté Bakarou , Diabaté Konimba , Diakité Abdoul Aziz , Diall Hawa , Dicko Fatoumata , Sylla Mariam , Bey Pierre , Desjardins Laurence , Gagnepain‐Lacheteau Anne , Coze Carole , Harif Mhamed , Doz François
Published: April 2018

Background

Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015.

Procedure

The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French‐African Paediatric Oncology Group.

Results

Eighty‐eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months–5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event‐free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8–81.2%) and 59% (95% CI 47.9–69.5%), respectively, with a median follow‐up of 3.7 years (0.1–5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource‐limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival.
Autism spectrum disorder assessment and evaluation research in 10 school psychology journals from 2007 to 2017
Authors: McClain Maryellen Brunson , Otero Tiffany L. , Haverkamp Cassity R. , Molsberry Fiona
Published: April 2018

School psychologists are increasingly engaged in service provisions for students eligible for special education services under the eligibility category of autism, including conducting school‐based assessments and evaluations. Evaluations occur for a variety of reasons such as special education eligibility decision‐making, treatment and intervention planning, and progress monitoring. Publications in school psychology journals emphasizing autism spectrum disorder (ASD) assessment and evaluation are vital to quality training and practitioner utilization of quality practices. In the current study, researchers conducted a systematic review of publicaftions in 10 school psychology journals from 2007 to 2017 to assess the current state of ASD assessment and evaluation research in the field of school psychology. Implications for researchers, trainers, and practitioners are discussed.