bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a procedure to quantify oxolinic acid, danofloxacin, ciprofloxacin and enrofloxacin in selected meats by micellar liquid chromatography according to EU Commission Decision 2002/657/EC
Authors: Peris‐Vicente Juan , Tayeb‐Cherif Khaled , Carda‐Broch Samuel , Esteve‐Romero Josep
Published: June 2017

The suitability of an analytical method to determine oxolinic acid, danofloxacin, ciprofloxacin and enrofloxacin in edible tissues, based on micellar liquid chromatography coupled with fluorescence detection, to be applied in chicken, turkey, duck, lamb, goat, rabbit and horse muscle, is described. The method was fully matrix‐matched in‐lab revalidated, for each antimicrobial drug and meat, following the guidelines of the EU Commission Decision 2002/657/EC. The permitted limits were the maximum residue limits stated by the EU Commission Regulation 37/2010. The results obtained for the studied validation parameters were in agreement with the guidelines: selectivity (the antibiotics were resolved), linearity (r2 > 0.995), limit of detection (0.004–0.02 mg/kg), limits of quantification (0.01–0.05 mg/kg), calibration range (up to 0.5 mg/kg), recovery (89.5–105.0%), precision (<8.3%), decision limit, detection capability, ruggedness, stability and application to incurred samples. The method was found to be able to provide reliable concentrations with low uncertainty within a large interval, including the maximum residue limits, and then was useful to find out prohibited contaminated samples. The method did not require to be adapted for these matrices, and then it maintained its interesting advantages: short‐time, eco‐friendly, safe, inexpensive, easy‐to‐conduct, minimal manipulation and useful for routine analysis.
Automated long‐term EEG analysis to localize the epileptogenic zone
Authors: van Mierlo Pieter , Strobbe Gregor , Keereman Vincent , Birot Gwénael , Gadeyne Stefanie , Gschwind Markus , Carrette Evelien , Meurs Alfred , Van Roost Dirk , Vonck Kristl , Seeck Margitta , Vulliémoz Serge , Boon Paul
Published: June 2017

Objective

We investigated the performance of automatic spike detection and subsequent electroencephalogram (EEG) source imaging to localize the epileptogenic zone (EZ) from long‐term EEG recorded during video‐EEG monitoring.

Methods

In 32 patients, spikes were automatically detected in the EEG and clustered according to their morphology. The two spike clusters with most single events in each patient were averaged and localized in the brain at the half‐rising time and peak of the spike using EEG source imaging. On the basis of the distance from the sources to the resection and the known patient outcome after surgery, the performance of the automated EEG analysis to localize the EZ was quantified.

Results

In 28 out of the 32 patients, the automatically detected spike clusters corresponded with the reported interictal findings. The median distance to the resection in patients with Engel class I outcome was 6.5 and 15 mm for spike cluster 1 and 27 and 26 mm for cluster 2, at the peak and the half‐rising time of the spike, respectively. Spike occurrence (cluster 1 vs. cluster 2) and spike timing (peak vs. half‐rising) significantly influenced the distance to the resection (p < 0.05). For patients with Engel class II, III, and IV outcomes, the median distance increased to 36 and 36 mm for cluster 1. Localizing spike cluster 1 at the peak resulted in a sensitivity of 70% and specificity of 100%, positive prediction value (PPV) of 100%, and negative predictive value (NPV) of 53%. Including the results of spike cluster 2 led to an increased sensitivity of 79% NPV of 55% and diagnostic OR of 11.4, while the specificity dropped to 75% and the PPV to 90%.

Significance

We showed that automated analysis of long‐term EEG recordings results in a high sensitivity and specificity to localize the epileptogenic focus.
Experimental evaluation of fog computing techniques to reduce latency in LTE networks
Authors: García‐Pérez César Augusto , Merino Pedro
Published: June 2017

The changes in new mobile networks toward a full Internet protocol–based architecture have led to opportunities for service‐oriented optimizations based on emergent technologies like fog computing, software‐defined networking, or network function virtualization. This paper explores 2 ways of using these new technologies to reduce the latency in Long‐Term Evolution (LTE) networks. Both solutions reduce the path that the data packets should follow from the base station (evolved Node B [eNB]) to the network components that connect to the servers. The first solution, called Fog Gateway, is based on the interception of the packets in the tunnel at the eNB and their redirection to local servers running the fog services. This solution is fully compliant with the current LTE architecture and only requires new components. The second solution, called General Packet Radio Service Tunneling Protocol Gateway (GTP), is based on splitting the eNB's functionality to avoid unnecessary GTP encapsulation of the packets geared toward the fog services. This paper includes an analysis of the latency split in LTE networks, the evaluation of both solutions with experiments in an end‐to‐end LTE network testbed, and a discussion around their applicability in future fifth‐generation networks. The results confirm that they are feasible to provide low‐latency services and that they are compatible with some of the emergent paradigms (software‐defined networking and network function virtualization) as well as with the studies on fifth‐generation networks from the standardization bodies.
Regulatory T‐cell conditioning endows activated effector T cells with suppressor function in autoimmune hepatitis/autoimmune sclerosing cholangitis
Authors: Liberal Rodrigo , Grant Charlotte R. , Yuksel Muhammed , Graham Jonathon , Kalbasi Alireza , Ma Yun , Heneghan Michael A. , Mieli‐Vergani Giorgina , Vergani Diego , Longhi Maria Serena
Published: June 2017

Imbalance between T regulatory (Treg) and T effector (Teff) cells is likely to contribute to the induction and perpetuation of liver damage in autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC) either through inability of Tregs to restrain proliferation and effector cytokine production by responders or through conversion of Tregs into T helper type 1 (Th1) or type 17 (Th17) effector lymphocytes. We investigated the effect of Treg skewing on the phenotypic and functional properties of CD4+CD127+CD25high cells, an activated subset of Teff, in 32 patients with AIH and 20 with AISC and in 36 healthy subjects. In AIH/AISC we noted a substantial increase in peripheral blood–derived CD4+CD127+ CD25high cells that display a Th1/Th17 phenotypic profile, as reflected by heightened interferon gamma and interleukin 17 (IL‐17) production as well as by high levels of T‐bet and related orphan receptor 3 expression, which is strongly correlated with disease activity. CD4+CD127+CD25high cells are unresponsive to low‐dose IL‐2 and in patients have marked proliferative ability, further enhanced by stimulation with IL‐7. CD4+CD127+CD25high cells obtained from CD4+ cells exposed to Treg polarizing conditions display enhanced IL‐10 production; up‐regulate CD49b and LAG‐3, markers of T regulatory 1 cells; and effectively suppress responder cell proliferation in both healthy subjects and AIH/AISC patients through a mechanism which is dependent on interferon gamma and IL‐17. The suppressive function of CD4+CD127+CD25high cells is maintained upon proinflammatory challenge in healthy subjects but not in AIH/AISC. Conclusion: Treg skewing confers activated Teff phenotypic and functional properties of T regulatory 1 cells in health and in AIH/AISC, though suppressive function is lost in patients upon proinflammatory challenge; protracted modulation of the inflammatory environment is required to attenuate the effector potential while boosting immunoregulatory properties in Teff. (Hepatology 2017;66:1570–1584).
Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case‐control study in southwest China
Authors: Zheng Chuanfen , Zeng Hui , Lin Hui , Wang Jia , Feng Xiaobin , Qiu Zhiqun , Chen Ji‐an , Luo Jiaohua , Luo Yang , Huang Yujing , Wang Lingqiao , Liu Wenyi , Tan Yao , Xu Anwei , Yao Yuan , Shu Weiqun
Published: June 2017

Microcystins have been reported to be carcinogenic by animal and cell experimentation, but there are no data on the linkage between serum microcystins and hepatocellular carcinoma (HCC) risk in humans. We conducted a clinical case‐control study to investigate the association between serum microcystins and HCC risk after controlling several known risk factors, such as hepatitis B virus, alcohol, and aflatoxin. From December 2013 to May 2016, 214 patients newly diagnosed with HCC along with 214 controls (frequency‐matched by age and sex) were recruited from three hospitals in Chongqing, southwest China. Basic information on lifestyle and history of disease was obtained by questionnaire. Blood samples were collected and analyzed for serum microcystin‐LR (MC‐LR) and aflatoxin‐albumin adduct by enzyme‐linked immunosorbent assay and for hepatitis B surface antigen status by chemiluminescence assay. Binary logistic regression analyses were performed to assess the independent effects of MC‐LR and its joint effects with other factors on HCC risk. The adjusted odds ratio for HCC risk by serum MC‐LR was 2.9 (95% confidence interval [CI], 1.5‐5.5) in all patients. Notably, a clear relationship between increased MC‐LR level (Q2, Q3, and Q4) and HCC risk was observed with elevated adjusted odds ratios (1.3, 2.6, and 4.0, respectively). Positive interactions with the additive model were investigated between MC‐LR and hepatitis B virus infection (synergism index = 3.0; 95% CI, 2.0‐4.5) and between MC‐LR and alcohol (synergism index = 4.0; 95% CI, 1.7‐9.5), while a negative interaction was found between MC‐LR and aflatoxin (synergism index = 0.4; 95% CI, 0.3‐0.7). Additionally, serum MC‐LR was significantly associated with tumor differentiation (r = –0.228, P < 0.001). Conclusion: We provide evidence that serum MC‐LR was an independent risk factor for HCC in humans, with an obvious positive interaction with hepatitis B virus and alcohol but a negative interaction with aflatoxin. (Hepatology 2017;66:1519–1528)
Branched chain α‐ketoacid dehydrogenase kinase 111–130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice
Authors: Krishnan Bharathi , Massilamany Chandirasegaran , Basavalingappa Rakesh H. , Gangaplara Arunakumar , Kang Guobin , Li Qingsheng , Uzal Francisco A. , Strande Jennifer L. , Delhon Gustavo A. , Riethoven Jean‐Jack , Steffen David , Reddy Jay
Published: June 2017

Introduction

Organ‐specific autoimmune diseases are believed to result from immune responses generated against self‐antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune‐mediated damage may be wide spread.

Methods

In this report, we describe a mitochondrial protein, branched chain α‐ketoacid dehydrogenase kinase (BCKDk) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.

Results

We demonstrate that BCKDk protein contains at least nine immunodominant epitopes, three of which, BCKDk 71–90, BCKDk 111–130 and BCKDk 141–160, were found to induce varying degrees of myocarditis in immunized mice. One of these, BCKDk 111–130, could also induce hepatitis without affecting lungs, kidneys, skeletal muscles, and brain. In immunogenicity testing, all three peptides induced antigen‐specific T cell responses, as verified by proliferation assay and/or major histocompatibility complex class II/IAk dextramer staining. Finally, the disease‐inducing abilities of BCKDk peptides were correlated with the production of interferon‐γ, and the activated T cells could transfer disease to naive recipients.

Conclusions

The disease induced by BCKDk peptides could serve as a useful model to study the autoimmune events of inflammatory heart and liver diseases.
Biphasic Effect of ATP on In Vitro Mineralization of Dental Pulp Cells
Authors: Techatharatip Oranuch , Nowwarote Nunthawan , Taebunpakul Suthisa , Pavasant Prasit
Published: June 2017

Dental pulp cells release adenosine triphosphate (ATP) in response to intrapulpal pressure and the amount released depends on the magnitude of the pressure. ATP regulates the differentiation of stem cells into adipocytes and osteoblasts. However, it is unknown whether extracellular ATP influences the stemness and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). Therefore, this study investigated the effects of extracellular ATP at a low (0.1 μM) and high (10 μM) concentration on the stemness and osteogenic differentiation of SHEDs. Cells were cultured in either growth medium or osteogenic medium with or without 0.1–10 μM ATP. In growth medium, both concentrations of ATP increased the mRNA expression of pluripotent and osteogenic markers. In contrast, in osteogenic medium, 0.1 μM ATP enhanced in vitro mineralization, whereas 10 μM ATP inhibited this process. In addition, 10 μM ATP stimulated the mRNA expression and activity of ectonucleotide pyrophosphatase/phosphodiesterase (ENPP), an enzyme that regulates the phosphate/pyrophosphate ratio. Thus, depending on the growth condition and its concentration, ATP stimulated stemness and in vitro mineralization or inhibited mineralization. In growth medium, both ATP concentrations stimulated pluripotent and osteogenic marker gene expression. However, in osteogenic medium, a biphasic effect was found on in vitro mineralization; the low concentration stimulated, whereas the high concentration inhibited, mineralization. We propose that ATP released due to mechanical stress modulates the stemness and differentiation of SHEDs. J. Cell. Biochem. 119: 488–498, 2018. © 2017 Wiley Periodicals, Inc.
A Novel Interacting Protein SERP1 Regulates the N‐Linked Glycosylation and Function of GLP‐1 Receptor in the Liver
Authors: Xiao Yuanyuan , Han Junfeng , Wang Qianqian , Mao Yueqin , Wei Meilin , Jia Weiping , Wei Li
Published: June 2017

Glucagon‐like peptide 1 (GLP‐1) exerts multiple effects on metabolism through its receptor, GLP‐1R, in the liver. Activation and transduction of GLP‐1R require complex interactions of largely unknown accessory proteins, and these processes are crucial to the response to endoplasmic reticulum (ER) stress. Using the membrane‐based split ubiquitin yeast two‐hybrid system (MYTH) and a human liver cDNA library, we obtained the human GLP‐1R interactome and identified SERP1 as a potential interacting protein based on its ability to stabilize membrane proteins and facilitate N‐linked glycosylation. GLP‐1R and SERP1 were co‐expressed in HEK‐293 cells, and their interaction was confirmed by co‐immunoprecipitation. We then found that overexpression of SERP1 could rescue GLP‐1R glycosylation after application of tunicamycin to block N‐linked glycosylation. SERP1 overexpression also attenuated exendin‐4‐stimulated cAMP accumulation and AMPK activation. However, the glycosylation and function of mutant GLP‐1R, in which all three sites for N‐linked glycosylation were mutated, were not increased with overexpression of SERP1. Moreover, as a GLP‐1R interactor, SERP1 could also partly reverse the accumulation of tunicamycin‐induced ER stress. Taken together, our findings identify a group of proteins that interact with GLP‐1R and show that one specific interacting protein, SERP1, has an important role in facilitating the glycosylation of GLP‐1R and rescuing its activities after ER stress induced by tunicamycin. J. Cell. Biochem. 118: 3616–3626, 2017. © 2017 Wiley Periodicals, Inc.
Humanized mouse models: Application to human diseases
Authors: Ito Ryoji , Takahashi Takeshi , Ito Mamoru
Published: June 2017

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft‐versus‐host disease.
Silver nanoparticle impregnated rechargeable polyethersulfone (PES) membrane for biofouling prevention and water disinfection
Authors: Biswas Pritam , Bandyopadhyaya Rajdip
Published: June 2017

BACKGROUND

Biofouling severely limits membrane life and performance. To address the twin challenges of biofouling prevention and water disinfection, silver nanoparticle (Ag‐NP) impregnated, sulfonated polyethersulfone (SPES) membrane was chosen.

RESULTS

By tuning the degree of sulfonation, Ag‐SPES‐1, Ag‐SPES‐2 and Ag‐SPES‐3 membranes were synthesized, having increasing Ag content of 4.1, 8.8 and 15.1 wt%, respectively. Time‐dependent confocal microscopy images of E. coli cells (after the passage of 104 CFU mL‐1) show that all attached E. coli cells were killed in 5, 2 and 2 min for Ag‐SPES‐1, Ag‐SPES‐2 and Ag‐SPES‐3 membranes, respectively. However, Ag‐SPES‐2 shows maximum permeability coefficient (452 L m‐2 h‐1 bar‐1) of decontaminated water in a cross‐flow module. This is because, Ag‐SPES‐1 takes a longer time for E. coli cell‐death due to its lowest Ag loading, whereas Ag‐SPES‐3 – due to excess Ag loading – results in the formation of an undesirable Ag‐NP layer on the membrane surface, leading to 16.7% decrease in its porosity. The latter translates into lower permeability. Fresh membranes showed the same permeability over six runs. However, to simulate the eventual depletion of Ag in the very long run, the membranes were recharged with Ag, upon which it showed similar permeability to a fresh membrane.

CONCLUSION

Therefore, the study achieved: (i) optimization of Ag content for highest permeability; (ii) recharging of membrane for prevention of biofouling‐initiation with both fresh and recharged Ag‐SPES membrane, leading to membrane reuse; and (iii) E. coli free disinfected water with Ag concentration (39 μg L‐1), well‐within the permissible limit for drinking‐water (100 μg L‐1). © 2017 Society of Chemical Industry
Prototype of a scaled‐up microbial fuel cell for copper recovery
Authors: Rodenas Motos Pau , Molina Gonzalo , ter Heijne Annemiek , Sleutels Tom , Saakes Michel , Buisman Cees
Published: June 2017

Background

Bioelectrochemical systems (BESs) enable recovery of electrical energy through oxidation of a wide range of substrates at an anode and simultaneous recovery of metals at a cathode. Scale‐up of BESs from the laboratory to pilot scale is a challenging step in the development of the process, and there are only a few successful experiences to build on. This paper presents a prototype BES for the recovery of copper.

Results

The cell design presented here had removable electrodes, similar to those in electroplating baths. The anode and cathode in this design could be replaced independently. The prototype bioelectrochemical cell consisted of an 835 cm2 bioanode fed with acetate, and a 700 cm2 cathode fed with copper. A current density of 1.2 A/−2 was achieved with 48 mW m−2 of power production. The contribution of each component (anode, electrolytes, cathode and membrane) was evaluated through the analysis of the internal resistance distribution. This revealed that major losses occurred at the anode, and that the design with removable electrodes results in higher internal resistance compared with other systems. To further assess the practical applicability of BES for copper recovery, an economic evaluation was performed.

Conclusion

Analysis shows that the internal resistance of several lab‐scale BESs is already sufficiently low to make the system economic, while the internal resistance for scaled‐up systems still needs to be improved considerably to become economically applicable.© 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Configurations containing a given linear hypergraph
Authors: Dukes Peter J. , Flowers Garret
Published: June 2017

We investigate the minimum order of a linear r‐regular k‐uniform hypergraph, also known as an ‐combinatorial configuration, which contains a given linear k‐uniform hypergraph of maximum (vertex) degree at most r.
Correlates between calcaneal morphology and locomotion in extant and extinct carnivorous mammals
Authors: Panciroli Elsa , Janis Christine , Stockdale Maximilian , Martín‐Serra Alberto
Published: June 2017

Locomotor mode is an important component of an animal's ecology, relating to both habitat and substrate choice (e.g., arboreal versus terrestrial) and in the case of carnivores, to mode of predation (e.g., ambush versus pursuit). Here, we examine how the morphology of the calcaneum, the ‘heel bone’ in the tarsus, correlates with locomotion in extant carnivores. Other studies have confirmed the correlation of calcaneal morphology with locomotion behaviour and habitat. The robust nature of the calcaneum means that it is frequently preserved in the fossil record. Here, we employ linear measurements and 2D‐geometric morphometrics on a sample of calcanea from eighty‐seven extant carnivorans and demonstrate a signal of correlation between calcaneal morphology and locomotor mode that overrides phylogeny. We used this correlation to determine the locomotor mode, and hence aspects of the palaeobiology of, 47 extinct carnivorous mammal taxa, including both Carnivora and Creodonta. We found ursids (bears), clustered together, separate from the other carnivorans. Our results support greater locomotor diversity for nimravids (the extinct ‘false sabertooths’, usually considered to be more arboreal), than previously expected. However, there are limitations to interpretation of extinct taxa because their robust morphology is not fully captured in the range of modern carnivoran morphology.
Pretarsal structures in Leiodidae and Agyrtidae (Coleoptera, Staphylinoidea)
Authors: Gnaspini Pedro , Antunes‐Carvalho Caio , Leschen Richard A. B.
Published: June 2017

We analysed pretarsal characters of 87 species of Leiodidae (including 10 cholevines and representatives of all tribes and ca. 60% of the genera of non‐cholevines), five species of Agyrtidae, and nine representatives of outgroup taxa (Hydraenidae, Staphylinidae, Hydrophilidae, and Histeridae) using scanning electron microscopy. We focused our observations on the architecture of the empodium (including the sclerites and associated setae), the shape and composition of the medial projection of the distal margin of the terminal tarsomere, and the armature of the claws, which were considered a promising source of information for delimiting supraspecific taxa in our previous study. We identified several diagnostic features and recognize potential synapomorphies at the tribal, subtribal and generic levels. The internal systematic arrangement and/or even the monophyletic status of most of the subfamilies of Leiodidae (Camiarinae, Catopocerinae, Leiodinae, and Platypsyllinae) are challenged. We identified potential synapomorphies for Camiarinae (Camiarini and Agyrtodini) and Leiodinae. The non‐monophyly of Cholevinae is possible because part of the tribe (Anemadini, Eucatopini, and Oritocatopini) shares potentially apomorphic features with Leiodinae (e.g., a triangular medial projection with a diagonal row of conical spines), whereas another part (Leptodirini and Ptomaphagini) shares a potentially apomorphic feature with Coloninae and Platypsyllinae (a typical medial projection with two distinct triangular projections).
Suppression of the vacuolar invertase gene delays senescent sweetening in chipping potatoes
Authors: Wiberley‐Bradford Amy E , Bethke Paul C
Published: June 2017

BACKGROUND

Potato chip processors require potato tubers that meet quality specifications for fried chip color, and color depends largely upon tuber sugar contents. At later times in storage, potatoes accumulate sucrose, glucose, and fructose. This developmental process, senescent sweetening, manifests as a blush of color near the center of the fried chip, becomes more severe with time, and limits the storage period. Vacuolar invertase (VInv) converts sucrose to glucose and fructose and is hypothesized to play a role in senescent sweetening. To test this hypothesis, senescent sweetening was quantified in multiple lines of potato with reduced VInv expression.

RESULTS

Chip darkening from senescent sweetening was delayed by about 4 weeks for tubers with reduced VInv expression. A strong positive correlation between frequency of dark chips and tuber hexose content was observed. Tubers with reduced VInv expression had lower hexose to sucrose ratios than controls.

CONCLUSION

VInv activity contributes to reducing sugar accumulation during senescent sweetening. Sucrose breakdown during frying may contribute to chip darkening. Suppressing VInv expression increases the storage period of the chipping potato crop, which is an important consideration, as potatoes with reduced VInv expression are entering commercial production in the USA. © 2017 Society of Chemical Industry
Targeted metabolomics analysis of aromatic amino acids and their gut microbiota–host cometabolites in rat serum and urine by liquid chromatography coupled with tandem mass spectrometry
Authors: Zeng Yifeng , Luo Liang , Hou Waner , Lu Biyu , Gong Jing , Chen Jiahui , Zhang Xiaojun , Han Bo , Xie Zhiyong , Liao Qiongfeng
Published: June 2017

Gut microbiota–host cometabolites are closely related to various diseases. Monitoring dynamic changes of cometabolites can provide a more comprehensive understanding of pathophysiology. Here, a novel liquid chromatography–tandem mass spectrometry method was performed for the analysis of aromatic amino acids and their gut microbiota–host cometabolites in rat serum and urine. In the developed method, seven key gut microbiota–host cometabolites were chromatographically separated on a Kinetex Phenyl‐Hexyl column by gradient elution, and the run time was 6 min. Serum and urine were extracted by protein precipitation. This method was linear between 10.20 and 1000.00 ng/mL for phenylalanine and p‐cresyl sulfate; 25.60–2500.00 ng/mL for tryptophan; 51.20–5000.00 ng/mL for tyrosine, indole, and indoxyl sulfate; and 75.50–7500.00 ng/mL for p‐cresol. The linearity, accuracy, precision, and recovery of seven analytes were all satisfactory. The method was sufficiently sensitive and robust. It was successfully applied to characterize the alterations of gut microbiota–host cometabolites in inflammatory disorders. All of these results suggest that the developed method is able to simultaneously monitor aromatic amino acids and their gut microbiota–host cometabolites. This method will be expected to be a valuable tool for clinical researches and comprehensive studies of the pathophysiological roles.
Pediatric cochlear implantation: Variation in income, race, payer, and charges across five states
Authors: Huang Zhen , Gordish‐Dressman Heather , Preciado Diego , Reilly Brian K.
Published: June 2017

Objectives/Hypothesis

Our objectives were to investigate pediatric cochlear implantation (PCI) across representative states within the United States and analyze any geographical differences in age, median household income, race, insurance, and total medical charges.

Study Design

Cross‐sectional.

Methods

Data from children (aged 0.5–18 years) who received cochlear implantation surgery were collected from the 2011 State Ambulatory Surgery and Services Databases from California (CA), Florida (FL), Maryland (MD), New York (NY), and Kentucky (KY) as a part of the Healthcare Cost and Utilization Project. We performed data analysis using a combination of Kruskal‐Wallis and Wilcoxon rank sum tests, as well as nominal logistic regression.

Results

Five hundred twelve cases of PCI were performed during 2011 across the five states. The overall mean and median age of implantation were 5.6 years and 4 years, respectively. There was no statistical difference in age of implantation across states (P = .85). However, there were statistical differences in primary payer (P < .001), median household income quartiles of patients who received an implant (P < .006), race (P < .001), and total median hospital charges for four of the states, with the exception of CA (P < .001).

Conclusions

Age of PCI appears to be similar across the five states in cross‐sectional analysis. Geographic variations in charges, payer, race, and median household income occur with statistical significance in PCI. Further analysis of contributing factors at each state level may help elucidate the root cause of these disparities and improve and justify a uniform approach to healthcare delivery and standards of care.

Level of Evidence

4. Laryngoscope, 128:954–958, 2018
Delivered adipose‐derived stromal cells improve host‐derived adipose tissue formation in composite constructs in vivo
Authors: Storck Katharina , Fischer Reyk , Buchberger Maria , Haller Bernhard , Regn Sybille
Published: June 2017

Objectives/Hypothesis

Adipose tissue engineering aims to provide functional tissue surrogates for the restoration of soft tissue defects and contour deformities in the face. Many studies involve the delivery of cells; however, the impact and the exact role of the implanted cells is not yet fully elucidated.

Study Design

Animal research.

Methods

In this study, we used a mouse model for the development of volume‐stable adipose tissue using polyurethane scaffolds combined with a long‐term stable fibrin gel and adipose‐derived stromal cells to investigate the influence of cell delivery on tissue development.

Results

After 12 weeks in vivo, the emerging tissue in these constructs was shown to be exclusively of host origin by human‐specific vimentin staining. Comparison of unseeded versus seeded scaffolds revealed a significant effect of the delivered cells on adipose tissue development as shown by histological staining and histomorphometric quantification of adipocytes, whereas blood vessel formation was not affected by delivery of adipose‐derived stromal cells at this time point.

Conclusions

This is evidence for an indirect action of the implanted cells, providing a proadipogenic microenvironment within constructs, which was further boosted by adipogenic precultivation of the seeded constructs. Especially in peripheral areas of the constructs, the number of adipocytes was significantly elevated in seeded scaffolds compared to nonseeded controls, suggesting that the implanted cells likely triggered the invasion and differentiation of host cells. This is supported by the fact that the provision of a fat rich environment (by coverage of the constructs with a fat flap upon implantation) additionally stimulated adipose tissue formation.

Level of Evidence

NA. Laryngoscope, 127:E428–E436, 2017
Cationic Nanohydrogel Particles for Therapeutic Oligonucleotide Delivery
Authors: Leber Nadine , Nuhn Lutz , Zentel Rudolf
Published: June 2017

Short pharmaceutical active oligonucleotides such as small interfering RNA (siRNA) or cytidine‐phosphate‐guanosine (CpG) are considered as powerful therapeutic alternatives, especially to medicate hard‐to‐treat diseases (e.g., liver fibrosis or cancer). Unfortunately, these molecules are equipped with poor pharmacokinetic properties that prevent them from translation. Well‐defined nanosized carriers can provide opportunities to optimize their delivery and guide them to their site of action. Among several concepts, this Feature Article focuses on cationic nanohydrogel particles as a universal delivery system for small anionic molecules including siRNA and CpG. Cationic nanohydrogels are derived from preaggregated precursor block copolymers, which are further cross‐linked to obtain well‐defined nanoparticles of tunable sizes and with (degradable) cationic cores. Novel opportunities for oligonucleotide delivery in vitro and in vivo with respect to liver fibrosis therapies will be highlighted as well as perspectives toward modulating the immune system. In general, the approach of covalently stabilized cationic carrier systems can contribute to find advanced oligonucleotide therapeutics.
K+‐Responsive Block Copolymer Micelles for Targeted Intracellular Drug Delivery
Authors: Yan Shan , Wan Lin‐Yan , Ju Xiao‐Jie , Wu Jiang‐Feng , Zhang Lei , Li Ming , Liu Zhuang , Wang Wei , Xie Rui , Chu Liang‐Yin
Published: June 2017

In this work, a novel type of block copolymer micelles with K+‐responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self‐assembly of poly(ethylene glycol)‐b‐poly(N‐isopropylacry‐lamide‐co‐benzo‐18‐crown‐6‐acrylamide) (PEG‐b‐P(NIPAM‐co‐B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA‐loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K+ concentration of 150 × 10−3m, as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC‐T6 and HepG2 cells responding to the increase of K+ concentration in intracellular compartments, which confirms the successful endocytosis and efficient K+‐induced intracellular release. Such K+‐responsive block copolymer micelles are highly potential as new‐generation of smart nanocarriers for targeted intracellular delivery of drugs.
Nuclear embeddings in function spaces
Authors: Triebel Hans
Published: June 2017

Let be the usual Besov spaces in bounded Lipschitz domains Ω in (bounded intervals if ). The paper clarifies under which conditions the continuous embedding between two such spaces with is nuclear.
Envisioning a future purchase: The effects of consumption imagery perspective and identity on consumer motivation
Authors: Soliman Monica , Buehler Roger , Peetz Johanna
Published: June 2017

When people visualize a potential purchase, they can adopt either a first‐person or a third‐person perspective. The present research examines whether the perspective adopted would affect consumer motivation, and whether this effect would depend on the extent to which the imagined purchase is connected to identity. In four studies, third‐person imagery resulted in stronger consumer motivation than first‐person imagery, but only for purchases that were tied closely to identity. Furthermore, the results suggest that the motivational effect of third‐person imagery is not based on concerns about others’ views of the self, but rather on the extent to which one feels that the imagined behavior is tied closely to identity.
Engaging fans on microblog: the synthetic influence of parasocial interaction and source characteristics on celebrity endorsement
Authors: Gong Wanqi , Li Xigen
Published: June 2017

Brand managers use celebrity microbloggers to endorse their products on microblogs. Previous studies on celebrity endorsement mechanisms concentrated on source factors such as celebrity's characteristics and celebrity—product congruence. This study introduces a new audience factor: the fan–celebrity parasocial interaction (PSI) to explore the celebrity endorsement mechanism within a microblog context. The study hypothesizes that PSI and source factors (credibility, attractiveness, and congruence) significantly influence endorsement effectiveness. The results of an online survey (N = 862) indicate that PSI and celebrity–product congruence are salient antecedents of endorsement effectiveness. PSI serves as a mediator of the effect of source attractiveness on endorsement effectiveness. Source credibility and celebrity–product congruence are mediators between PSI and endorsement effectiveness. The study develops and tests a conceptual model to illustrate the influential mechanism of celebrity endorsement on microblog platforms.
Mild cognitive impairment as a risk factor for Parkinson's disease dementia
Authors: Hoogland Jeroen , Boel Judith A. , de Bie Rob M.A. , Geskus Ronald B. , Schmand Ben A. , Dalrymple‐Alford John C. , Marras Connie , Adler Charles H. , Goldman Jennifer G. , Tröster Alexander I. , Burn David J. , Litvan Irene , Geurtsen Gert J. ,   on behalf of the MDS Study Group “Validation of Mild Cognitive Impairment in Parkinson Disease”
Published: June 2017

Background

The International Parkinson and Movement Disorder Society criteria for mild cognitive impairment in PD were recently formulated.

Objectives

The aim of this international study was to evaluate the predictive validity of the comprehensive (level II) version of these criteria by assessment of their contribution to the hazard of PD dementia.

Methods

Individual patient data were selected from four separate studies on cognition in PD that provided information on demographics, motor examination, depression, neuropsychological examination suitable for application of level II criteria, and longitudinal follow‐up for conversion to dementia. Survival analysis evaluated the predictive value of level II criteria for cognitive decline toward dementia as expressed by the relative hazard of dementia.

Results

A total of 467 patients were included. The analyses showed a clear contribution of impairment according to level II mild cognitive impairment criteria, age, and severity of PD motor symptoms to the hazard of dementia. There was a trend of increasing hazard of dementia with declining neuropsychological performance.

Conclusions

This is the first large international study evaluating the predictive validity of level II mild cognitive impairment criteria for PD. The results showed a clear and unique contribution of classification according to level II criteria to the hazard of PD dementia. This finding supports their predictive validity and shows that they contribute important new information on the hazard of dementia, beyond known demographic and PD‐specific factors of influence. © 2017 International Parkinson and Movement Disorder Society
New structural classes of antituberculosis agents
Authors: Kumar Vajinder , Patel Sanjay , Jain Rahul
Published: June 2017

Tuberculosis (TB), one of the deadliest diseases is shattering the health and socioeconomic status of the society. The emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains has provided unprecedented lethal character to TB. The development of MDR and XDR strains of TB results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. Because of the development of rapid resistance byMycobacterium tuberculosis, researchers are confronted with serious challenges in combating TB. For instance, the need for potency and specificity in therapeutic agents approaching clinics, and the increasing demand of low toxicity due to long duration of treatment. Recently, it is proposed that such challenges could be addressed by a shift from contemporary or known classes of drugs to new scaffold‐containing or entirely new structural classes of drugs that possibly act on the previously unknown targets, resulting in possibly less instances of resistance development. The exploitation of advances made in the biology of TB in the last and present decades have created opportunities to discover a large number of new structural classes that specifically targets TB by molecular mechanism of action(s) unknown earlier. We have earlier reviewed new structural classes of anti‐TB agents up to year 2005. This review covers literature reports of the subsequent 10 years on the discovery of new structural classes of synthetic anti‐TB agents. Due to the availability of large number of research reports, we have divided new compounds in 38 structural classes, 368 structures, and 307 references.
A modified regularized algorithm for a semilinear space‐fractional backward diffusion problem
Authors: Jiang Xiaoying , Xu Dinghua , Zhang Qifeng
Published: June 2017

In this paper, we investigate a backward problem for a space‐fractional partial differential equation. The main purpose is to propose a modified regularization method for the inverse problem. The existence and the uniqueness for the modified regularized solution are proved. To derive the gradient of the optimization functional, the variational adjoint method is introduced, and hence, the unknown initial value is reconstructed. Finally, numerical examples are provided to show the effectiveness of the proposed algorithm. Copyright © 2017 John Wiley & Sons, Ltd.
Dynamic nuclear polarization studies of nitroxyl spin probes in agarose gel using Overhauser‐enhanced magnetic resonance imaging
Authors: Meenakumari V. , Utsumi Hideo , Hyodo Fuminori , Jawahar A. , Milton Franklin Benial A.
Published: June 2017

Agarose is a tissue‐equivalent material and its imaging characteristics similar to those of real tissues. Hence, the dynamic nuclear polarization studies of 3‐carboxy‐2,2,5,5‐tetramethyl‐pyrrolidine‐1‐oxyl (carboxy‐PROXYL) in agarose gel were carried out. The dynamic nuclear polarization parameters such as spin lattice relaxation time, longitudinal relaxivity, leakage factor, saturation parameter and coupling parameter were estimated for 2 mM carboxy‐PROXYL in phosphate‐buffered saline solution and water/agarose mixture (99 : 1). From these results, the spin probe concentration was optimized as 2 mM, and the reduction in enhancement was observed for carboxy‐PROXYL in water/agarose mixture (99 : 1) compared with phosphate‐buffered saline solution. Phantom imaging was also performed with 2 mM concentration of carboxy‐PROXYL in various concentrations of agarose gel at various radio frequency power levels. The results from the dynamic nuclear polarization measurements agree well with the phantom imaging results. These results pave the way for designing model system for human tissues suited to the biological applications of electron spin resonance/Overhauser‐enhanced magnetic resonance imaging.
Effects of pedunculopontine nucleus stimulation on human bladder function
Authors: Roy Holly A. , Pond Debbie , Roy Christopher , Forrow Beth , Foltynie Thomas , Zrinzo Ludvic , Akram Harith , Aziz Tipu Z. , FitzGerald James J. , Green Alexander L.
Published: June 2017

Aims

The pedunculopontine nucleus (PPN) is a deep brain stimulation target for Parkinson's disease (PD). Unilateral PPN stimulation has been described in a previous case report to provoke urinary frequency, urgency and detrusor overactivity, due to probable activation of the pontine micturition center. Our aim was to evaluate the effect of bilateral PPN DBS on urodynamic parameters and to investigate the likely mechanisms using probabilistic tractography.

Methods

Six male PD subjects with bilateral PPN deep brain stimulators were recruited. Urodynamic bladder filling assessments were carried out with the stimulators ON and OFF. Two subjects also had diffusion‐weighted and T1‐weighted MRI scans performed and probabilistic tractography was carried out to describe white matter connections with the stimulated area.

Results

Five subjects completed urodynamic testing. PPN DBS did not give rise to detrusor overactivity or lower sensory thresholds during bladder filling. However, there was a significant increase in maximal bladder capacity with stimulation: mean bladder volume at maximal capacity was 199 mL (range 103‐440) ON stimulation compared with 131 mL (range 39‐230) OFF stimulation. Tractography demonstrated extensive connectivity to cortical and subcortical regions, some of which have been implicated in bladder control. Fiber pathways also passed close to the vicinity of the pontine micturition center.

Conclusions

Bilateral PPN DBS did not have a detrimental effect on urodynamic filling parameters or produce detrusor overactivity, but did slightly increase maximal capacity. Possible mechanisms include long‐range connectivity or local effects at the pontine micturition center.
Impact of direct epispinal stimulation on bladder and bowel functions in pigs: A feasibility study
Authors: Guiho Thomas , Delleci Claire , Azevedo‐Coste Christine , Fattal Charles , Guiraud David , Vignes Jean‐Rodolphe , Bauchet Luc
Published: June 2017

Aims

This study assesses the potential of epispinal (subdural) stimulation application in the treatment of urinary and bowel neurological disorders. Acute experiments were performed on a large animal model — the domestic pig — to develop a new methodology facilitating future results and technology transfers to human.

Methods

After rectal and bladder catheterization, four Landrace pigs (45‐50 kg) underwent spinal cord surgery — that is, lumbosacral incision, laminectomy [L4‐S4], dural opening and microsurgical arachnoid dissection. Three successive electrical stimulation sessions were carried out: 1) nerve roots stimulation, 2) epispinal stimulation with a matrix electrode, 3) epispinal stimulation with a small diameter needle electrode. Changes in rectal and bladder pressures were monitored throughout the various procedures to identify spinal areas inducing responses while evaluating the influence of electrode contacts size in the measured responses amplitudes.

Results

An interesting area was identified in the upper portion of the spinal myelomeres (ie, spinal cord segment delimited by two successive pairs of spinal roots) directly adjoining root with best pressures (either rectal or vesical). Significant responses (up to 40 cmH2O) were also obtained with a needle electrode. Furthermore, bowel evacuation was triggered in one of the animals. Despite the use of smaller electrode contacts, no detrusor or rectum selective responses were observed in none of the sessions.

Conclusion

This study showed, for the first time, that epispinal stimulation causes significant detrusor and rectal responses in pigs and allows considering further studies with the objective of treating urinary and rectal disorders in spinal cord injury patients.
Atypical teratoid/rhabdoid tumors in children treated with multimodal therapies: The necessity of upfront radiotherapy after surgery
Authors: Lee Jeongshim , Kim Dong‐Seok , Han Jung Woo , Suh Chang‐Ok
Published: June 2017

Background

Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant pediatric brain tumor with a dismal prognosis. We evaluated the efficacy of multimodal therapy in children with ATRT.

Procedure

Nine children diagnosed with cranial ATRT, who received multimodal therapy between 2005 and 2014, including surgical resection followed by radiotherapy (RT), systemic chemotherapy (CT), and high‐dose chemotherapy/stem cell transplantation (HDCT/SCT), were analyzed retrospectively. The median age at diagnosis was 32 months. Initial treatment included surgery in eight patients (88%), CT in all (100%), RT in eight (88%), and HDCT/SCT in seven (78%).

Results

The median follow‐up period for survivors was 21 months. The 2‐year progression‐free rate was 66.7%. Two patients had progression 4 and 17 months after diagnosis. One received multimodal treatment, including surgery and upfront CT with delayed RT; the other underwent surgery and upfront CT without RT. The 2‐year event‐free survival and overall survival rates were 46.7% and 62.2%, respectively. Hematologic toxicity of grade 3 or more was observed in six patients treated with HDCT/SCT and two who underwent craniospinal irradiation. Deaths were attributed to progressive disease (n = 2) and treatment‐related toxicity (n = 2) from sepsis and acute respiratory failure after CT and HDCT/SCT.

Conclusions

Maximal safe resection in conjunction with upfront RT is a reasonable multimodal treatment in patients with ATRT for prolonging progression‐free survival. Further research may help determine the optimal parameters for reducing treatment toxicity, such as intensity of HDCT/SCT and the RT field.