bluuebunny/crossref_metadata_2025 huggingface dataset:
A field‐applicable method for flow cytometric analysis of granulocyte activation: Cryopreservation of fixed granulocytes
Authors: de Ruiter Karin , van Staveren Selma , Hilvering Bart , Knol Edward , Vrisekoop Nienke , Koenderman Leo , Yazdanbakhsh Maria
Published: March 2018

Upon activation granulocytes upregulate several adhesion molecules (CD11b) and granule proteins (CD35, CD66b) and shed surface l‐selectin (CD62L). These changes in expression, as assessed by flow cytometry, can be used as markers for activation. Whereas these markers are usually studied in fresh blood samples, a new method is required when samples are collected at a field site with no direct access to a flow cytometer. Therefore, we developed and tested a field‐applicable method in which fixed leukocytes were cryopreserved. Using this method, the intensity of granulocyte activation markers was compared to samples that were either stained fresh, or fixed prior to staining but not cryopreserved. In addition, the response to an in vitro stimulation with fMLF was determined. While we observed differences in marker intensities when comparing fresh and fixed granulocytes, similar intensities were found between fixed cells that had been cryopreserved and fixed cells that did not undergo cryopreservation. Although fixation using FACS lysing solution might lead to membrane permeabilization, activation markers, and the responsiveness to fMLF or eotaxin could still be clearly measured. This method will, therefore, enable future studies of granulocyte activation in settings with limited resources and will allow simultaneous analysis of samples collected at different time points. © 2018 International Society for Advancement of Cytometry
ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis
Authors: Das Koushik K. , Heeg Steffen , Pitarresi Jason R. , Reichert Maximilian , Bakir Basil , Takano Shigetsugu , Kopp Janel L. , Wahl‐Feuerstein Anja , Hicks Philip , Sander Maike , Rustgi Anil K.
Published: March 2018

Background: The plasticity of pancreatic acinar cells to undergo acinar to ductal metaplasia (ADM) has been demonstrated to contribute to the regeneration of the pancreas in response to injury. Sox9 is critical for ductal cell fate and important in the formation of ADM, most likely in concert with a complex hierarchy of, as yet, not fully elucidated transcription factors. Results: By using a mouse model of acute pancreatitis and three dimensional organoid culture of primary pancreatic ductal cells, we herein characterize the Ets‐transcription factor Etv5 as a pivotal regulator of ductal cell identity and ADM that acts upstream of Sox9 and is essential for Sox9 expression in ADM. Loss of Etv5 is associated with increased severity of acute pancreatitis and impaired ADM formation leading to delayed tissue regeneration and recovery in response to injury. Conclusions: Our data provide new insights in the regulation of ADM with implications in our understanding of pancreatic homeostasis, pancreatitis and epithelial plasticity. Developmental Dynamics 247:854–866, 2018. © 2018 Wiley Periodicals, Inc.
Hippo‐yap signaling in ocular development and disease
Authors: Lee Matthew , Goraya Navneet , Kim Seonhee , Cho Seo‐Hee
Published: March 2018

The Hippo‐Yes associated protein (Yap) pathway plays an important role in organ size control by regulating cell proliferation, apoptosis, and stem cell renewal. Hippo‐Yap signaling also functions at the level of cellular development in a variety of organs through its effects on cell cycle control, cell survival, cell polarity, and cell fate. Because of its important roles in normal development and homeostasis, abnormal regulation of this pathway has been shown to lead to pathological outcomes such as tissue overgrowth, tumor formation, and abnormal organogenesis, including ocular‐specific disorders. In this review, we summarize how normal and perturbed control of Yap signaling is implicated in ocular development and disease Developmental Dynamics 247:794–806, 2018. © 2018 Wiley Periodicals, Inc.
Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development
Authors: Harley Randall J. , Murdy Joseph P. , Wang Zhirong , Kelly Michael C. , Ropp Tessa‐Jonne F. , Park Sehoon H. , Maness Patricia F. , Manis Paul B. , Coate Thomas M.
Published: March 2018

Background: In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. Neuronal cell adhesion molecule (NrCAM) is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. Results: Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells. Neonatal Nrcam‐null cochleae show errors in type II SGN fasciculation, reduced efferent innervation, and defects in the stereotyped packing of hair and supporting cells. Nrcam loss also leads to dramatic changes in the profiles of presynaptic afferent and efferent synaptic markers at the time of hearing onset. Despite these numerous developmental defects, Nrcam‐null adults do not show defects in auditory acuity, and by postnatal day 21, the developmental deficits in ribbon synapse distribution and sensory domain structure appear to have been corrected. Conclusions: NrCAM is expressed by several neural and sensory epithelial subtypes within the developing cochlea, and the loss of Nrcam confers numerous, but nonpermanent, developmental defects in innervation and sensory domain patterning. Developmental Dynamics 247:934–950, 2018. © 2018 Wiley Periodicals, Inc.
Generation of Elf5‐Cre knockin mouse strain for trophoblast‐specific gene manipulation
Authors: Kong Shuangbo , Liang Guixian , Tu Zhaowei , Chen Dunjin , Wang Haibin , Lu Jinhua
Published: March 2018

Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells. To analyze the specificity and efficiency of Cre recombinase activity in Elf5‐Cre mice, we mated Elf5‐Cre mice with Rosa26mT/mG reporter mice, and found that Elf5‐Cre transgene is expressed specifically in the trophoectoderm as early as embryonic day 4.5 (E4.5). By E12.5, the activity of Elf5‐Cre transgene was detected exclusively in all derivatives of trophoblast lineages, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. In addition, Elf5‐Cre transgene was also active during spermatogenesis, from spermatids to mature sperms, which is consistent with the endogenous Elf5 expression in testis. Collectively, our results provide a unique tool to delete specific genes selectively and efficiently in trophoblast lineage during placentation.
Associations of parents' self, child, and other “fat talk” with child eating behaviors and weight
Authors: Lydecker Janet A. , Riley Kristen E. , Grilo Carlos M.
Published: March 2018

Objective

Fat talk, negative communication about weight, is common in the media, peer groups, and families. Little is known about parental fat talk directed at oneself or others. This study examined associations between different forms of parental fat talk and child disordered eating behaviors and weight, and differences by child sex and age.

Method

Parents of preadolescents or adolescents (n = 581) reported fat talk about themselves (self‐fat talk), others (obesity‐fat talk), and their child (child‐fat talk).

Results

76.0% of parents reported regular self‐fat talk in front of children, 51.5% reported obesity‐fat talk, and 43.6% reported child‐fat talk. Fat talk did not differ significantly between parents of preadolescents and adolescents but was more common with sons than daughters. Of the three forms of fat talk, only child‐fat talk was associated with all child eating and weight variables (binge eating, overeating, secretive eating, and overweight/obesity); associations were strongest for adolescent girls. Child sex was associated with secretive eating and overweight/obesity.

Conclusions

Parents reported using different forms of fat talk frequently. Parent self‐ and obesity‐fat talk were reported more frequently, but child‐fat talk was the most strongly associated with children's eating and weight. Because of associations with disordered eating behaviors, intervening to reduce fat talk might contribute to improving pediatric disordered eating and weight‐related interventions.
A hierarchical Bayesian model to incorporate uncertainty into methods for diversity partitioning
Authors: Marion Zachary H. , Fordyce James A. , Fitzpatrick Benjamin M.
Published: March 2018

Recently there have been major theoretical advances in the quantification and partitioning of diversity within and among communities, regions, and ecosystems. However, applying those advances to real data remains a challenge. Ecologists often end up describing their samples rather than estimating the diversity components of an underlying study system, and existing approaches do not easily provide statistical frameworks for testing ecological questions. Here we offer one avenue to do all of the above using a hierarchical Bayesian approach. We estimate posterior distributions of the underlying “true” relative abundances of each species within each unit sampled. These posterior estimates of relative abundance can then be used with existing formulae to estimate and partition diversity. The result is a posterior distribution of diversity metrics describing our knowledge (or beliefs) about the study system. This approach intuitively leads to statistical inferences addressing biologically motivated hypotheses via Bayesian model comparison. Using simulations, we demonstrate that our approach does as well or better at approximating the “true” diversity of a community relative to naïve or ad‐hoc bias‐corrected estimates. Moreover, model comparison correctly distinguishes between alternative hypotheses about the distribution of diversity within and among samples. Finally, we use an empirical ecological dataset to illustrate how the approach can be used to address questions about the makeup and diversities of assemblages at local and regional scales.
Size‐Controllable Synthesis of NiMoS Nanoflowers for Hydrodesulfurization – Space‐Confinement Effect of Silica Nanospheres
Authors: Song Wenjing , Lai Weikun , Lian Yixin , Yang Weimin , Jiang Xingmao
Published: March 2018

The edge sites of NiMoS are highly catalytically active and are preferred over the surfaces. However, the stacking of the NiMoS layers is thermodynamically favored and limits the exposure of the active surface. Herein, we engineer the nanoflower structure to expose surface active sites through the synthesis of NiMoS nanoflowers assembled from ultrathin nanosheets. The well‐controlled fabrication of small NiMoS nanoflowers under the assistance of small silica nanospheres exposes abundant active sites. The exposed active sites and high surface area lead to superior hydrodesulfurization performance.
Spectroscopic Studies of Photochemical Transformations of Cymantrenylquinazolinone Derivatives
Authors: Kelbysheva Elena S. , Telegina Lyudmila N. , Strelkova Tatyana V. , Ezernitskaya Mariam G. , Nosova Emiliya V. , Borisov Yurii A. , Lokshin Boris V. , Loim Nikolay M.
Published: March 2018

For the first time, the photochemical properties of compounds 1–4 containing a cymantrene fragment at the 2‐ or 3‐position of the quinazolinone have been studied. It was found that the ‐NC=O group in compounds 1 and 2 is capable of coordinating to the Mn atom with the formation of intramolecular chelates. The influence of the nature of the solvent and substituent in the side‐chain of cymantrene on the thermodynamic and kinetic stability of the dicarbonyl complexes was studied. For the first time, the olefin chelate 9 was isolated; its structure was established by X‐ray diffraction analysis and its photochemical and fluorescence properties were studied. The photolysis of compound 4 gave only stable intermolecular dicarbonyl complexes, in which the solvent can be easily replaced by n‐ and π‐donor ligands.
Synthesis of CLA‐Rich Lysophosphatidylcholine by Immobilized MAS1‐H108A‐Catalyzed Esterification: Effects of the Parameters and Monitoring of the Reaction Process
Authors: Li Daoming , Wang Weifei , Zhang Li , Liu Nan , Faiza Muniba , Tan Chin Ping , Yang Bo , Lan Dongming , Wang Yonghua
Published: March 2018

Conjugated linoleic acid (CLA)‐rich lysophosphatidylcholine (LPC) with many proven beneficial effects is successfully synthesized by an immobilized mutant lipase (MAS1‐H108A)‐catalyzed esterification of glycerophosphorylcholine (GPC) and CLA‐rich FAs. Under the optimized conditions (temperature of 55 °C, substrate molar ratio of CLA‐rich FAs to GPC of 40:1, and enzyme loading of 300 U g−1), LPC content as high as 89.10 mol.% is achieved, which is exceptionally higher than any ever‐reported value. By monitoring the esterification process, it is found that sn1‐LPC is easy to synthesize and is the predominant product, while sn2‐LPC and phosphatidylcholine (PC) are difficult to synthesize and are with lower content in the final product. The formed sn2‐LPC during esterification may mainly attribute to the acyl migration of sn1‐LPC and the ratio of sn1‐LPC to sn2‐LPC finally plateaus at approximately 7. Besides, our results also demonstrate that sn2‐LPC is the main template for the synthesis of PC. Finally, a complete reaction scheme for the synthesis of LPC by immobilized MAS1‐H108A‐catalyzed esterification of GPC and fatty acids is mapped out. Overall, the highest LPC content can be obtained by immobilized MAS1‐H108A‐catalyzed esterification and there is the first study for systematical studying the reaction process of CLA‐rich LPC synthesis.

Practical Applications: Previous studies have demonstrated that Novozym 435 is the most suitable catalyst for the synthesis of CLA‐rich LPC. However, the LPC content obtained by Novozym 435 is only 70 mol.% and the reaction process for the synthesis of CLA‐rich LPC has not been studied systematically, which restricts the commercial production of CLA‐rich LPC in some extent. Therefore, further exploration of alternative enzyme resources for highly efficient synthesis of CLA‐rich LPC and trying to clarify the reaction process of CLA‐rich LPC synthesis are of significant importance for the future commercially industrial production of CLA‐rich LPC.

A complete reaction scheme for the synthesis of LPC using GPC and FAs as substrates by immobilized MAS1‐H108A‐catalyzed esterification. CLA‐rich FAs are used as model FAs in this study. Reaction parameters, such as temperature, CLA‐rich FAs/GPC ratio, and enzyme loading are selected to study their effects on the esterification. Concurrently, the reaction process is monitored. LPC content as high as 89.10 mol.% is obtained, which is the highest reported value thus far for the synthesis of CLA‐rich LPC. Finally, the reaction scheme for the synthesis of LPC by immobilized MAS1‐H108A‐catalyzed esterification is mapped out.
Green/Yellow‐Emitting Conjugated Heterocyclic Fluorophores for Luminescent Solar Concentrators
Authors: Papucci Costanza , Geervliet Tristan A. , Franchi Daniele , Bettucci Ottavia , Mordini Alessandro , Reginato Gianna , Picchioni Francesco , Pucci Andrea , Calamante Massimo , Zani Lorenzo
Published: March 2018

In this study, we report on the synthesis of new organic fluorophores containing either the benzo[1,2‐d:4,5‐d′]bisthiazole or the dithieno[3,2‐b:2′,3′‐d]silole heterocyclic unit, and on their application for the fabrication of luminescent solar concentrators (LSCs) made of poly(methyl methacrylate) (PMMA) thin films. In solution, the new compounds absorbed light in the visible region and displayed a brilliant green emission in the 500–600 nm range with moderate‐to‐good fluorescence quantum yields (0.25–0.68). Dispersions of selected fluorophores in PMMA thin films mostly maintained the light absorption features observed in solution, although in the case of benzobisthiazole‐based fluorophore 1a an evident fluorescence red‐shift was observed when increasing the compound concentration in the film. In agreement with its promising optical properties, LSCs prepared with the latter compound yielded interesting optical efficiencies up to 6.42 %, not far from those of state‐of‐the‐art PMMA LSC devices.
Non‐covalent Functionalization of Multi‐wall Carbon Nanotubes with Polyarginine: Characterization and Analytical Applications for Uric Acid Quantification
Authors: Gutiérrez Alejandro , Gutierrez Fabiana , Eguílaz Marcos , Parrado Concepción , Rivas Gustavo A.
Published: March 2018

We report for the first time the non‐covalent functionalization of multiwall carbon nanotubes (MWCNTs) with polyarginine (Polyarg), the modification of glassy carbon electrodes (GCE) with the resulting Polyarg‐MWCNTs dispersion and the analytical application of Polyarg‐MWCNTs‐modified GCE for the quantification of uric acid. The optimum MWCNT‐Polyarg dispersion was obtained by sonicating for 5.0 min the mixture of 0.75 mg mL−1 MWCNTs and 0.50 mg mL−1 Polyarg. The dispersion was characterized by scanning electron microscopy, electrophoretic mobility, electrochemical impedance spectroscopy, cyclic voltammetry and amperometry. The presence of MWCNT‐Polyarg at GCE surface produced a drastic decrease in the overvoltages for the oxidation of hydrogen peroxide (300 mV) ascorbic acid (281 mV) and uric acid (70 mV) and for the reduction of hydrogen peroxide (200 mV), as well as an important decrease in the charge transfer resistances for hydrogen peroxide, hydroquinone/quinone and ferricyanide/ferrocyanide markers. The strong adsorption of uric acid at GCE/MWCNT‐Polyarg made possible the highly sensitive detection of this biomarker at nanomolar levels even in the presence of 1.0×10−4 M ascorbic acid by Adsorptive Stripping with medium exchange and linear scan voltammetry transduction. The quantification of uric acid in untreated human urine was very successful, demonstrating an excellent correlation (98 %) with the reference method used in clinical laboratories (Uricostat, Wiener Lab).
Electrochemistry Study of Antineoplastic Raltitrexed Oxidation Mechanism and its Interaction with DNA
Authors: Queiroz Nathalia L. , Nascimento Maysa L. , Nascimento José A. M. , Nascimento Valberes B. , Oliveira Severino Carlos B.
Published: March 2018

Raltitrexede (RTX) is a folate analogue that belongs to the antimetabolites family and has antineoplastic activity correlated to inhibition of the thymidylate synthase (TS) enzyme. This study addresses the electrochemical characterization of RTX at a glassy carbon electrode, on a wide interval of pH, using voltammetric techniques. The interaction between RTX and double helix DNA (dsDNA) in physiological medium is also addressed, using a DNA‐electrochemical biosensor. A mechanism for the electrochemical oxidation of RTX is proposed. RTX is irreversibly electroxidized under a predominantly diffusion controlled and pH‐dependent process. The oxidation process in acid and physiological media occurs in two consecutive steps. The first oxidation step is pH‐independent and associated with the transfer of one electron of the nitro group at N10 position by releasing a methyl cation. The second oxidation step is pH‐dependent and occurs with the transfer of one electron and one proton from the carbon at C9 position, followed by a direct attack by a water molecule leading to an irreversible dissociation of an oxidation product of RTX. A strong interaction between RTX and dsDNA was revealed by using a multilayer dsDNA electrochemical biosensor. The experiments demonstrated that RTX interacts and binds to the dsDNA helix by different interaction modes, suggesting an intercalation in between the DNA base pairs leading to defects in its secondary structure.
Detection of Rocuronium in Whole Blood Using a Lipid‐bonded Conducting Polymer and Porous Carbon Composite Electrode
Authors: Chung Saeromi , Hwang Boo‐Young , Naveen M. H. , Shim Yoon‐Bo
Published: March 2018

Rocuronium is a neuromuscular blocking agent used in anesthesia to facilitate tracheal intubation by muscle relaxation. A fast and sensitive amperometric sensor was developed for the detection of rocuronium in human whole blood samples. The sensor probe was fabricated using phosphatidylinositol lipid (PI) bonded 3′‐(2‐aminopyrimidyl)‐2,2′ : 5′,2′′‐terthiophene and porous carbon, which revealed the enhanced response to the rocuronium oxidation. The modified sensor layers were characterized by electrochemical and surface analysis experiments. The experimental parameters affecting the rocuronium analysis were studied in terms of PI concentration, amount of porous carbon, pH, temperature, and interferences. A dynamic range was observed between 0.025 to 10 μg/mL with the detection limit of 3.83±0.21 ng/mL. The reliability of proposed sensor was successfully demonstrated through the detection of rocuronium in clinical samples without pre‐treatment.
Application of the CometChip platform to assess DNA damage in field‐collected blood samples from turtles
Authors: Sykora Peter , Chiari Ylenia , Heaton Andrew , Moreno Nickolas , Glaberman Scott , Sobol Robert W.
Published: March 2018

DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism‐induced oxidative damage that can lead to single‐strand and double‐strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra‐violet light, can also contribute to exogenously derived DNA damage. We previously validated a novel, high through‐put approach to measure levels of DNA damage in cultured mammalian cells. This new CometChip Platform builds on the classical single cell gel electrophoresis or comet methodology used extensively in environmental toxicology and molecular biology. We asked whether the CometChip Platform could be used to measure DNA damage in samples derived from environmental field studies. To this end, we determined that nucleated erythrocytes from multiple species of turtle could be successfully evaluated in the CometChip Platform to quantify levels of DNA damage. In total, we compared levels of DNA damage in 40 animals from two species: the box turtle (Terrapene carolina) and the red‐eared slider (Trachemys scripta elegans). Endogenous levels of DNA damage were identical between the two species, yet we did discover some sex‐linked differences and changes in DNA damage accumulation. Based on these results, we confirm that the CometChip Platform allows for the measurement of DNA damage in a large number of samples quickly and accurately, and is particularly adaptable to environmental studies using field‐collected samples. Environ. Mol. Mutagen. 59:322–333, 2018. © 2018 Wiley Periodicals, Inc.
Different outcomes, psychopathological features, and comorbidities in patients with eating disorders reporting childhood abuse: A 3‐year follow‐up study
Authors: Castellini Giovanni , Lelli Lorenzo , Cassioli Emanuele , Ciampi Eleonora , Zamponi Francesco , Campone Beatrice , Monteleone Alessio Maria , Ricca Valdo
Published: March 2018

The aim of this study was to evaluate the role of childhood adversities in long‐term outcomes in eating disorders (EDs). One hundred thirty‐three eating disorder patients were studied by means of the Structured Clinical Interview for DSM‐IV and psychometric tests, at baseline, at the end of individual cognitive behavioural therapy, and at 3‐year follow‐up. As compared with the other patients, those reporting childhood abuse (overall: 24.8%; physical abuse: 20.3%; sexual abuse: 13.6%) showed higher impulsivity, psychiatric comorbidity, lower full recovery at follow‐up (12.1% vs. 31%), and higher diagnostic crossover (39.4% vs. 13.0%). The different rates of recovery were mostly due to a higher persistence of depression in abused patients (77.8% vs. 26.7%). Patients with both abuse and neglect had a higher probability of dropout. Eating disorder patients with childhood abuse represent a group of persons with more complex psychopathological features and a worse long‐term outcome, thus requiring specific treatment strategies.
The impact of data frequency on market efficiency tests of commodity futures prices
Authors: Wu Xuedong , Dorfman Jeffrey H. , Karali Berna
Published: March 2018

We investigate the impacts of sampling frequency and model specification uncertainty on the outcome of unit root tests, commonly employed as market efficiency tests, using a new, robust Bayesian test on seven commodity futures prices at three different sample frequencies (daily, weekly, and monthly). Using Bayesian model averaging to account for different possible mean and error variance specifications, we show that sample frequency does affect the unit root test results: the higher the frequency, the higher the support for stationarity. We further show that not accounting for model specification uncertainty can produce unit root test results that are not robust.
Constraining the denudation process in the eastern Sichuan Basin, China using low‐temperature thermochronology and vitrinite reflectance data
Authors: Zhu Chuanqing , Qiu Nansheng , Liu Yifeng , Xiao Yao , Hu Shengbiao
Published: March 2018

The temperature history of samples and maximum palaeogeothermal profiles of boreholes were reconstructed based on low‐temperature thermochronology and vitrinite reflectance data, and the results provide limits for the timescale and amount of uplift–denudation of the eastern Sichuan Basin. The thermal history showed that the uplifting and cooling of eastern Sichuan Basin began around the Late Cretaceous (approximately 100–80 Ma). The region had experienced a continuous cooling process from the Late Cretaceous until the present, with the geothermal gradient decreasing from 32–36 °C/km to 20–23 °C/km. The amount of denudation at the Puguang region in north‐eastern Sichuan was approximately 2.3 km, whereas that at south‐eastern Sichuan was 1.9 km, and the erosion thickness in the eastern Sichuan fold belt that was revealed via the field samples is 2.3 ± 0.3–2.6 ± 0.3 km. The north‐eastern Sichuan experienced sustained cooling with inconspicuous fluctuations, whereas the thrust belt and the south‐eastern Sichuan Basin presented 2–4 stages with different cooling rates. It may indicate that the eastern Sichuan fold belt experienced a complex structural evolution, characterized by episodic upliftings and deformations since Late Cretaceous, while a different and gentle deformation took place in the northeastern Sichuan Basin.
Listening under difficult conditions: An activation likelihood estimation meta‐analysis
Authors: Alain Claude , Du Yi , Bernstein Lori J. , Barten Thijs , Banai Karen
Published: March 2018

The brain networks supporting speech identification and comprehension under difficult listening conditions are not well specified. The networks hypothesized to underlie effortful listening include regions responsible for executive control. We conducted meta‐analyses of auditory neuroimaging studies to determine whether a common activation pattern of the frontal lobe supports effortful listening under different speech manipulations. Fifty‐three functional neuroimaging studies investigating speech perception were divided into three independent Activation Likelihood Estimate analyses based on the type of speech manipulation paradigm used: Speech‐in‐noise (SIN, 16 studies, involving 224 participants); spectrally degraded speech using filtering techniques (15 studies involving 270 participants); and linguistic complexity (i.e., levels of syntactic, lexical and semantic intricacy/density, 22 studies, involving 348 participants). Meta‐analysis of the SIN studies revealed higher effort was associated with activation in left inferior frontal gyrus (IFG), left inferior parietal lobule, and right insula. Studies using spectrally degraded speech demonstrated increased activation of the insula bilaterally and the left superior temporal gyrus (STG). Studies manipulating linguistic complexity showed activation in the left IFG, right middle frontal gyrus, left middle temporal gyrus and bilateral STG. Planned contrasts revealed left IFG activation in linguistic complexity studies, which differed from activation patterns observed in SIN or spectral degradation studies. Although there were no significant overlap in prefrontal activation across these three speech manipulation paradigms, SIN and spectral degradation showed overlapping regions in left and right insula. These findings provide evidence that there is regional specialization within the left IFG and differential executive networks underlie effortful listening.
Detailed spatiotemporal brain mapping of chromatic vision combining high‐resolution VEP with fMRI and retinotopy
Authors: Pitzalis Sabrina , Strappini Francesca , Bultrini Alessandro , Di Russo Francesco
Published: March 2018

Neuroimaging studies have identified so far, several color‐sensitive visual areas in the human brain, and the temporal dynamics of these activities have been separately investigated using the visual‐evoked potentials (VEPs). In the present study, we combined electrophysiological and neuroimaging methods to determine a detailed spatiotemporal profile of chromatic VEP and to localize its neural generators. The accuracy of the present co‐registration study was obtained by combining standard fMRI data with retinotopic and motion mapping data at the individual level. We found a sequence of occipito activities more complex than that typically reported for chromatic VEPs, including feed‐forward and reentrant feedback. Results showed that chromatic human perception arises by the combined activity of at the least five parieto‐occipital areas including V1, LOC, V8/VO, and the motion‐sensitive dorsal region MT+. However, the contribution of V1 and V8/VO seems dominant because the re‐entrant activity in these areas was present more than once (twice in V8/VO and thrice in V1). This feedforward and feedback chromatic processing appears delayed compared with the luminance processing. Associating VEPs and neuroimaging measures, we showed for the first time a complex spatiotemporal pattern of activity, confirming that chromatic stimuli produce intricate interactions of many different brain dorsal and ventral areas.
Postoperative mechanical bowel obstruction after pharyngolaryngectomy for hypopharyngeal cancer: Retrospective analysis using a Japanese inpatient database
Authors: Suzuki Sayaka , Yasunaga Hideo , Matsui Hiroki , Fushimi Kiyohide , Ando Mizuo , Yamasoba Tatsuya
Published: March 2018

Background

Data have been limited on donor‐site mechanical bowel obstruction after pharyngolaryngectomy with free jejunum graft reconstruction.

Methods

Using a nationwide Japanese inpatient database, we extracted data on patients who underwent pharyngolaryngectomy for hypopharyngeal cancer between July 2007 and March 2014. A Cox proportional hazard model was used to determine the association between background characteristics and the occurrence of mechanical bowel obstruction.

Results

Among the 3320 eligible patients from 332 hospitals, 108 patients (3.3%) developed mechanical bowel obstruction after a median 88 (interquartile range 26‐217) postoperative days. Multivariable Cox regression analysis revealed that older age (≥60 years old) was independently associated with an increased risk of mechanical bowel obstruction, whereas sex, body mass index [BMI], smoking status, comorbidity at admission, blood transfusion, history of surgery, and hospital type were not.

Conclusion

In pharyngolaryngectomy, careful attention should be paid to the risk of abdominal complications and, thus, to the graft choice, especially in elderly patients.
Circulating tumor DNA as a biomarker and liquid biopsy in head and neck squamous cell carcinoma
Authors: Payne Karl , Spruce Rachel , Beggs Andrew , Sharma Neil , Kong Anthony , Martin Timothy , Parmar Satyesh , Praveen Prav , Nankivell Paul , Mehanna Hisham
Published: March 2018

The use of circulating biochemical molecular markers in head and neck cancer holds the promise of improved diagnostics, treatment planning, and posttreatment surveillance. In this review, we provide an introduction for the head and neck surgeon of the basic science, current evidence, and future applications of circulating tumor DNA (ctDNA) as a biomarker and liquid biopsy to detect tumor genetic heterogeneity in patients with head and neck squamous cell carcinoma (HNSCC).
Cost‐effectiveness analysis of salvage therapies in locoregional previously irradiated head and neck cancer
Authors: Kim HaYeon , Vargo John A. , Beriwal Sushil , Clump David A. , Ohr James P. , Ferris Robert L. , Heron Dwight E. , Huq M. Saiful , Smith Kenneth J.
Published: March 2018

Background

The purpose of this study was to present our evaluation of the cost‐effectiveness of salvage therapies for patients with recurrent head and neck cancer.

Methods

A Markov model was developed with 5 salvage treatment strategies: (1) platinum‐based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity‐modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost‐effectiveness ratio (ICER), with effectiveness in quality‐adjusted life years (QALYs), and evaluated with a willingness‐to‐pay (WTP) threshold of $100 000 per QALY gained.

Results

In the base case analysis, no treatment strategy was cost‐effective at a WTP threshold. The most cost‐effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost‐effective.

Conclusion

None of the treatment strategies were cost‐effective. However, SBRT‐based reirradiation has potential to be cost‐effective.
Association of overexpressed karyopherin alpha 2 with poor survival and its contribution to interleukin‐1β‐induced matrix metalloproteinase expression in oral cancer
Authors: Wang Chun‐I , Yu Chia‐Jung , Huang Yenlin , Yi Jui‐Shan , Cheng Hsing‐Wen , Kao Huang‐Kai , Lao William Wei‐Kai , Chang Kai‐Ping
Published: March 2018

Background

The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression.

Methods

The KPNA2 expressions were analyzed by immunohistochemistry and enzyme‐linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2‐knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real‐time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor‐kappa B (NF‐κB).

Results

The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease‐specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)‐1β‐induced nuclear import of NF‐κB and MMP (MMP‐1, MMP‐3, and MMP‐9) transcription.

Conclusion

The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP‐mediated metastasis.
Pilot randomized controlled trial of a comprehensive smoking cessation intervention for patients with upper aerodigestive cancer undergoing radiotherapy
Authors: Rettig Eleni M. , Fakhry Carole , Hales Russell K. , Kisuule Flora , Quon Harry , Kiess Ana P. , Yin Linda X. , Zhang Yuehan , Blackford Amanda L. , Drummond M. Bradley , Gourin Christine G. , Koch Wayne M. , Eisele David W. , D'Souza Gypsyamber
Published: March 2018

Background

Smoking among patients with cancer is associated with poor outcomes, however, smoking cessation interventions have had limited success.

Methods

This randomized controlled trial compared a novel smoking cessation intervention (“intervention”) with enhanced usual care (“control”). Participants were smokers with head and neck or thoracic malignancies undergoing radiation. Controls received brief counseling. Intervention participants received intensive counseling, pharmacotherapy, text‐messaging, and financial incentives. Biochemically confirmed 7‐day abstinence at 8 weeks was compared using Fisher's exact t test. Smoking abstinence and intensity were also analyzed using time‐series panel regression.

Results

The study population comprised 19 intervention and 10 control participants. More intervention (74%) than control (30%) participants abstained from smoking at 8 weeks (P = .05). Intervention participants were significantly more likely to abstain (adjusted odds ratio [OR] 14.70; 95% confidence interval [CI] 3.56‐60.76) and smoked fewer cigarettes (adjusted incidence rate ratio [IRR], 0.16; 95% CI 0.06‐0.40) during weeks 1 to 8.

Conclusion

This intervention decreased smoking among patients with upper aerodigestive cancers during radiotherapy.
Impact of Interferon Lambda 4 Genotype on Interferon‐Stimulated Gene Expression During Direct‐Acting Antiviral Therapy for Hepatitis C
Authors: Ramamurthy Narayan , Marchi Emanuele , Ansari M. Azim , Pedergnana Vincent , Mclean Angela , Hudson Emma ,   STOP HCV consortium, Bowden Rory , Spencer Chris C.A. , Barnes Eleanor , Klenerman Paul
Published: March 2018

New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat, including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, patients with cirrhosis receiving a 16‐week course of sofosbuvir and ribavirin had a sustained virological response (SVR) rate of around 50%. In patients with cirrhosis, interferon lambda 4 (IFNL4) CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon‐stimulated gene (ISG) signature in peripheral blood and in liver at baseline. Unexpectedly, patients with the CC genotype showed a dynamic increase in ISG expression between weeks 4 and 16 of DAA therapy, whereas the reverse was true for non‐CC patients. Conclusion: These data provide an important dynamic link between host genotype and phenotype in HCV therapy also potentially relevant to naturally acquired infection. (Hepatology 2018; 00:000‐000).
Hepatology in a changing health care landscape: A call for health services research
Authors: VanWagner Lisa B. , Kanwal Fasiha
Published: March 2018

With the passage of the Affordable Care Act followed by the physician payment reform, there is an urgent need to better understand the complex relationships between structure (including incentives), processes, and outcomes of health care and, based on this understanding, identify interventions that can ensure delivery of high‐value care to patients with liver disease. As hepatologists, how do we systematically address these issues and ensure that we provide high‐value care to our patients? These factors combine in the burgeoning field of health services research. This article seeks to describe how health services research influences the practice of hepatology, the tools and technologies it utilizes, as well as how interested individuals can seek to acquire knowledge and methodological training in health services research. Finally, we summarize the current state of health services research in hepatology and liver transplantation. (Hepatology 2018).
Drivers behind widespread informal payments in the Romanian public health care system: From tolerance to corruption to socio‐economic and spatial patterns
Authors: Horodnic Adrian V. , Mazilu Sorin , Oprea Liviu
Published: March 2018

In order to explain informal payments in public health care services in Romania, this paper evaluates the relationship between extra payments or valuable gifts (apart from official fees) and the level of tolerance to corruption, as well as the socio‐economic and spatial patterns across those individuals offering informal payments. To evaluate this, a survey undertaken in 2013 is reported. Using logistic regression analysis, the findings are that patients with a high tolerance to corruption, high socio‐economic risk (those divorced, separated, or with other form of marital status, and those not working), and located in rural or less affluent areas are more likely to offer (apart from official fees) extra payments or valuable gifts for health care services. The paper concludes by discussing the health policy implications.
Human resources for health: A narrative review of adequacy and distribution of clinical and nonclinical human resources in hospitals of Iran
Authors: Nobakht Samin , Shirdel Arash , Molavi‐Taleghani Yasamin , Doustmohammadi Mohammad M. , Sheikhbardsiri Hojjat
Published: March 2018

Introduction

Human resource supply is considered as one of the most vital factors in achieving organizational goals, and human resources are the most valuable factor in the production and delivery of services. Labor shortages and surpluses could downgrade the quality of services offered to patients. Considering the seriousness of this issue, this study aimed to investigate the status of human resources in Iran hospitals.

Methods

The narrative review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines. The key terms “Human Resource,” “Human Resource Management,” “Staff,” “Workforce,” “Hospital,” “emergency,” “staff nursing,” “medical,” “clinical personnel,” “administration,” “physician personnel,” “non clinical personnel,” “hospital personnel,” “human development,” and “Iran” were used in combination with Boolean operators OR and AND. The Institute for Scientific Information's Web of Science, PubMed, Scopus, ScienceDirect, Ovid, ProQuest, Wiley, Google Scholar, and the Persian database were searched.

Results

The research findings revealed that Iran's hospitals have no uniform distribution of human resources. In spite of the concentration of labor forces in some positions (eg, laboratory, radiology, operating room, anesthesia, and midwifery), other positions occupied by physicians and nurses are experiencing serious shortages of human resources, affecting the quality of the provided services.

Conclusion

With respect to the study findings, planning to compensate for staff shortages and achieving personnel standard levels as well as providing the grounds for training the heads of wards for proper human resource management and planning would lead to an increase in the efficiency and effectiveness of hospital activities.
Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks
Authors: Kikuchi Asuka , Nasir Fairuz Binti Mohammadi , Inami Akie , Mohsen Attayeb , Watanuki Shoichi , Miyake Masayasu , Takeda Kazuko , Koike Daigo , Ito Takayasu , Sasakawa Junpei , Matsuda Rin , Hiraoka Kotaro , Maurer Marcus , Yanai Kazuhiko , Watabe Hiroshi , Tashiro Manabu
Published: March 2018

Objective

Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.

Methods

In this double‐blind, placebo‐controlled, three‐way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two‐back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near‐infrared spectroscopy.

Results

Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.

Conclusions

Physiological “coupling” between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.
The Grasping Task: A 12‐month predictor of 24‐month delay task performance and BRIEF‐P inhibition scores
Authors: Neale Dave , Basilio Marisol , Whitebread David
Published: March 2018

Important developments in executive function are thought to occur during the second year of life, but few tools exist to assess executive function in this period. We argue that, to be effective, tasks for this age range need to reduce the abstract nature of the task rules and reduce reliance on verbal instruction. We present the Grasping Task, which uses familiar objects presented in such a way as to communicate the rules of the task to infants with no need for verbal instruction or abstraction. A longitudinal validity study of infants from 12 to 24 months old showed the Grasping Task at 12 months predicted children's performance on delay tasks and scores on the inhibition scale of the Behavior Rating Inventory of Executive Function for preschool children at 24 months but were unrelated to scores on the Bayley Scales of Infant Development III at 18 months, suggesting the task captures an aspect of early inhibitory development that is distinct from general cognitive functioning.

Highlights

We assessed the predictive validity of the grasping task, a new measure of emerging inhibitory skills in infancy.

Grasping task scores at 12 months predicted children's delay task scores and BRIEF‐P inhibition scores at 24 months.

The grasping task could be an important new tool in understanding the emergence and development of inhibitory control in infancy.
Chemical Waves in Embryonic Cell Cycles
Authors: Ferree Patrick L. , Di Talia Stefano
Published: March 2018

In most metazoans, early embryonic development is characterized by a rapid series of cleavage divisions. At the core of the coordination of these divisions is the oscillatory dynamic of Cyclin‐dependent kinase 1 (Cdk1), which arises through the integration of a negative feedback with delay and positive feedback. The regulation of this oscillator in large embryos is emerging as an ideal model for quantitative studies of how spatiotemporal coordination is achieved in large complex tissues. Recent work has demonstrated that the reaction‐diffusion dynamics regulating the cell cycle can generate traveling waves of enzymatic activity, which ensure the synchronization of cell division processes. Here, we will review how the mechanisms of cell cycle regulation can give rise to chemical waves, and highlight recent experiments on the coordination of cell division through traveling waves.