bluuebunny/crossref_metadata_2025 huggingface dataset:
Fronto‐temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia
Authors: Abram Samantha V. , Wisner Krista M. , Fox Jaclyn M. , Barch Deanna M. , Wang Lei , Csernansky John G. , MacDonald Angus W. , Smith Matthew J.
Published: October 2016

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting‐state functional connectivity between data‐driven networks, or components (referred to as, inter‐component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter‐component connectivity at rest using a group‐matched schizophrenia and control sample. We then assessed whether inter‐component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity‐symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter‐component connectivity, a medial‐fronto‐temporal metric and an orbito‐fronto‐temporal metric were related to cognitive empathy. Moreover, the medial‐fronto‐temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111–1124, 2017. © 2016 Wiley Periodicals, Inc.
On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance‐weighted principal component analysis
Authors: Martinez‐Murcia Francisco Jesús , Lai Meng‐Chuan , Górriz Juan Manuel , Ramírez Javier , Young Adam M. H. , Deoni Sean C. L. , Ecker Christine , Lombardo Michael V. ,   MRC AIMS Consortium,, Baron‐Cohen Simon , Murphy Declan G. M. , Bullmore Edward T. , Suckling John
Published: October 2016

Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large‐scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi‐modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site‐related variance, statistically significant group differences were found, including Broca's area and the temporo‐parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208–1223, 2017. © 2016 Wiley Periodicals, Inc.
Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck
Authors: van Weert Stijn , Reinhard Rinze , Bloemena Elisabeth , Buter Jan , Witte Birgit I. , Vergeer Marije R. , Leemans C. René
Published: October 2016

Background

We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease.

Methods

A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured. Distant disease‐free survival (DDFS) and time to death since distant metastases diagnosis were analyzed.

Results

Forty‐two percent of the patients were diagnosed with distant metastases. DDFS showed significant negative associations with advanced T classification, N+ classification, solid type tumor, and positive surgical margins. Distant metastases (91%) developed in the first 5 years after presentation. Median distant metastatic survival was 13.8 months. The most frequent organ sited was the lung. Solid type ACC showed a preponderance for multiorgan metastases (17/28; 61%). Distant metastases seemed not to occur in case of clear surgical margins. Solid type ACC had a significant poorer survival after development of distant metastases.

Conclusion

Metastatic ACC is not always an indolent disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 456–463, 2017
Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis
Authors: Hu Hongli , Zhu Wenwei , Qin Jun , Chen Min , Gong Liyan , Li Long , Liu Xiangyuan , Tao Yongzhen , Yin Huiyong , Zhou Hu , Zhou Lisha , Ye Dan , Ye Qinghai , Gao Daming
Published: October 2016

Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein–binding protein–associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. Conclusion: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515‐528).
An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis
Authors: Atiq Omair , Tiro Jasmin , Yopp Adam C. , Muffler Adam , Marrero Jorge A. , Parikh Neehar D. , Murphy Caitlin , McCallister Katharine , Singal Amit G.
Published: October 2016

Although surveillance ultrasound and alpha fetoprotein (AFP) tests have minimal direct harm, downstream harms from follow‐up tests must be weighed against surveillance benefits when determining the value of hepatocellular carcinoma (HCC) screening programs. Our study's aims were to characterize prevalence and correlates of surveillance benefits and harms in cirrhosis patients undergoing HCC surveillance. We conducted a retrospective cohort study among patients with cirrhosis followed at a safety‐net health system between July 2010 and July 2013. We recorded surveillance‐related benefits, defined as early tumor detection and curative treatment, and surveillance‐related physical harms, defined as computed tomography or magnetic resonance imaging scans, biopsies, or other procedures performed for false‐positive or indeterminate surveillance results. Sociodemographic and clinical correlates of surveillance harms were evaluated using multivariable logistic regression. We identified 680 patients with cirrhosis, of whom 78 (11.5%) developed HCC during the 3‐year study period. Of the 48 (61.5%) HCCs identified by surveillance, 43.8% were detected by ultrasound, 31.2% by AFP, and 25.0% by both surveillance tests. Surveillance‐detected patients had a higher proportion of early HCC (70.2% vs. 40.0%; P = 0.009), with no difference in tumor stage between ultrasound‐ and AFP‐detected tumors (P = 0.53). Surveillance‐related physical harms were observed in 187 (27.5%) patients, with a higher proportion of ultrasound‐related harm than AFP‐related harm (22.8% vs. 11.4%; P < 0.001). Surveillance‐related harms were associated with elevated ALT (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.26‐2.76), thrombocytopenia (OR, 2.06; 95% CI, 1.26‐3.38), and hepatology subspecialty care (OR, 1.63; 95% CI, 1.09‐2.42). Conclusion: Over one fourth of patients with cirrhosis experience physical harm for false‐positive or indeterminate surveillance tests—more often related to ultrasound than AFP. Interventions are needed to reduce surveillance‐related harm to increase the value of HCC screening programs in clinical practice. (Hepatology 2017;65:1196‐1205).
Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis
Authors: Das Sukanta , Maras Jaswinder Singh , Hussain Md. Shabir , Sharma Shvetank , David Paul , Sukriti Sukriti , Shasthry Saggere Muralikrishna , Maiwall Rakhi , Trehanpati Nirupama , Singh Tej P. , Sarin Shiv Kumar
Published: October 2016

Albumin is a potent scavenger of reactive oxygen species (ROS). However, modifications in albumin structure may reduce its antioxidant properties and modulate its immune‐regulatory functions. We examined alterations in circulating albumin in severe alcoholic hepatitis (SAH) patients and their contribution to neutrophil activation, intracellular stress, and alteration in associated molecular pathways. Albumin modifications and plasma oxidative stress were assessed in SAH patients (n = 90), alcoholic cirrhosis patients (n = 60), and healthy controls (n = 30) using liquid chromatography/mass spectrometry and spectrophotometry. Activation and intracellular ROS were measured in healthy neutrophils after treatment with purified albumin from the study groups. Gene expression of SAH neutrophils was analyzed and compared to gene expression from healthy neutrophils after stimulation with purified albumin from SAH patient plasma. SAH‐albumin showed the highest albumin oxidative state (P < 0.05) and prominent alteration as human nonmercaptalbumin 2 (P < 0.05). Plasma oxidative stress (advanced oxidative protein product) was higher in SAH versus alcoholic cirrhosis patients and healthy controls (P < 0.05). Neutrophil gelatinase‐associated lipocalin, myeloperoxidase, and intracellular ROS levels were highest in SAH‐albumin‐treated neutrophils (P < 0.05). Genes associated with neutrophil activation, ROS production, intracellular antioxidation, and leukocyte migration plus genes for proinflammatory cytokines and various toll‐like receptors were overexpressed in SAH neutrophils compared to healthy neutrophils (P < 0.05). Expression of the above‐mentioned genes in SAH‐albumin‐stimulated healthy neutrophils was comparable with SAH patient neutrophils, except for genes associated with apoptosis, endoplasmic reticulum stress, and autophagy (P < 0.05). Conclusions: In patients with SAH, there is a significant increase in albumin oxidation, and albumin acts as a pro‐oxidant; this promotes oxidative stress and inflammation in SAH patients through activation of neutrophils. (Hepatology 2017;65:631‐646).
Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study
Authors: Kaikkonen Jari E. , Würtz Peter , Suomela Emmi , Lehtovirta Miia , Kangas Antti J. , Jula Antti , Mikkilä Vera , Viikari Jorma S.A. , Juonala Markus , Rönnemaa Tapani , Hutri‐Kähönen Nina , Kähönen Mika , Lehtimäki Terho , Soininen Pasi , Ala‐Korpela Mika , Raitakari Olli T.
Published: October 2016

Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis‐related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty‐eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population‐based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34‐49 years (19% prevalence). Cross‐sectional associations as well as 4‐year and 10‐year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age‐adjusted and sex‐adjusted cross‐sectional analyses). The strongest direct associations were observed for extremely large very‐low‐density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48‐6.78), other very‐low‐density lipoprotein measures, and branched‐chain amino acids (e.g., leucine OR = 2.94, 2.51‐3.44). Strong inverse associations were observed for high‐density lipoprotein measures, e.g., high‐density lipoprotein size (OR = 0.36, 0.30‐0.42) and several fatty acids including omega‐6 (OR = 0.37, 0.32‐0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491‐500).
REFLECTION IN HOME VISITING: THE WHAT, WHY, AND A BEGINNING STEP TOWARD HOW
Authors: Tomlin Angela M. , Hines Elesia , Sturm Lynne
Published: October 2016

The work of home visitors in early childhood fields may include addressing many challenges to achieving curricular outcomes, including issues such as maintaining boundaries and managing one's own reactions to children, parents, and overall family situations. Increasingly, reflective supervision and consultation are recognized as a way for workers in home‐visiting early intervention and early care fields to address these personal and professional challenges and build competence (Watson, Gatti, Cox, Harrison, & Hennes, ). The features of home visiting that make reflective supervision/consultation essential are discussed. Next, results of a pilot project in which a sample of Part C early intervention providers respond to a vignette portraying a challenging parent–child interaction are briefly presented and discussed. Despite often stating the importance of relationships, participants did not identify concrete methods of supporting relationship or demonstrate recognition of parallel process. In addition, providers seldom endorsed the use of reflective skills such as observing, listening, wondering, or reflecting (Weatherston, ), and no providers discussed a need for reflective supervision/consultation. We suggest that these findings illustrate some of the areas in which early intervention home visitors could benefit from participation in reflective supervision/consultation to move from identifying reflective skills as important to actually being able to use such skills in their work with families.
Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process‐affected water: evidence for inhibition of P‐glycoprotein
Authors: Alharbi Hattan A. , Alcorn Jane , Al‐Mousa Ahmed , Giesy John P. , Wiseman Steve B.
Published: October 2016

Oil sands process‐affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco‐2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability‐glycoprotein, P‐gp). Neutral and basic fractions of OSPW inhibited activity of P‐gp in Caco‐2 cells by 1.9‐ and 2.0‐fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P‐gp) and malathion (not a substrate of P‐gp), were used as model chemicals to investigate inhibition of P‐gp in larvae. Co‐exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co‐exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co‐exposed with the extract of OSPW. The terminal elimination half‐life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non‐acute exposures, basic and neutral organic compounds in the water‐soluble fraction of OSPW inhibit activity of P‐gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.
Experimental and computational examination of anastellin (FnIII1c)–polymer interactions
Authors: Mallinson David , Cheung David L. , Simionesie Dorin , Mullen Alexander B. , Zhang Zhenyu J. , Lamprou Dimitrios A.
Published: October 2016

Using a combination of experimental and computational approaches, the interaction between anastellin, a recombinant fragment of fibronectin, and representative biomaterial surfaces has been examined. Anastellin and superfibronectin have been seen to exhibit antiangiogenic properties and other properties that may make it suitable for consideration for incorporation into biomaterials. The molecular interaction was directly quantified by atomic force microscope (AFM)‐based force spectroscopy, complemented by adsorption measurements using quartz crystal microbalance (QCM). Using AFM, it was found that the anastellin molecule facilitates a stronger adhesion on polyurethane films (72.0 pN nm−1) than on poly (methyl methacrylate) films (68.6 pN nm−1). However, this is not consistent with the QCM adsorption measurements, which show no significant difference. Molecular dynamics simulations of the behavior of anastellin on polyurethane in aqueous solution were performed to rationalize the experimental data, and show that anastellin is capable of rapid adsorption to PU while its secondary structure is stable upon adsorption in water. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 737–745, 2017.
Properties of the DASS‐21 in an Australian Community Adolescent Population
Authors: Shaw T. , Campbell M.A. , Runions K.C. , Zubrick S. R.
Published: October 2016

Background

Although developed for adults, the Depression Anxiety Stress Scales‐Short Version (DASS‐21) has been used in many research studies with adolescent samples. Evidence as to the applicability of the DASS subscale scores to represent the distinct states of depression, anxiety, and stress as experienced by adolescents is mixed, and the age at which it may be possible to differentiate these 3 states using the DASS‐21 has not yet been determined.

Objective

This study evaluated evidence for a multifactor structure in the DASS‐21 in adolescents and the specificity of the 3 subscales for adolescents in general and at different ages.

Method

Data were from a large cross‐sectional survey of 2,873 school students in Grades 6–12 (aged 12–18 years) in Australia. We conducted confirmatory bifactor analyses testing a general mental health distress factor and 3 domain‐specific factors for anxiety, depression, and stress for the whole sample and across gender by age groups. The internal consistency reliability of the DASS total and subscale scores was determined using omega coefficients.

Results

Analyses identified that most of the variation in the items was explained by the dominance of a single, general factor and the subscales lacked specificity across all age groups.

Conclusion

The DASS‐21 can be reliably used to measure general distress in adolescents, but the subscales fail to discriminate between the 3 states. Our results indicate that this lack of discrimination does not reduce with increasing age. These findings caution against the use of adult theoretical models and measures within adolescent populations.
Functional Roles of Eph A‐Ephrin A1 System in Endometrial Luminal Epithelial Cells During Early Pregnancy
Authors: Lim Whasun , Bae Hyocheol , Bazer Fuller W. , Song Gwonhwa
Published: October 2016

Eph and ephrin regulate diverse biological events such as proliferation, adhesion, migration, and angiogenesis through cell‐to‐cell interactions. However, little is known of their functional role and mechanisms of action in uterine endometrial cells. In the present study, we demonstrated the effects of the Eph and ephrin on interactions between blastocysts and endometrial luminal epithelial (pLE) cells in the pig that is regarded as an excellent biomedical animal model for research on the peri‐implantation period of pregnancy. Results of this study indicated that among eight members of the Eph A family, expression of Eph A1, A2, A4, and A7 was strongly detected in endometrial epithelial cells during early pregnancy. Of these, for identification of signal transduction pathways induced by ephrin A1, a major ligand for Eph A, cell proliferation assays, and immunofluorescence and cell cycle regulation were analyzed following treatment of pLE cells with ephrin A1. Ephrin A1 stimulated proliferation of pLE cells as evidenced by abundant PCNA expression and an increase in the G2/M phase. Western blot analysis showed that ephrin A1 activated PI3K and MAPK signaling proteins in a time‐dependent manner. Moreover, phosphorylation of AKT, ERK1/2, P38, and JNK proteins were suppressed by their inhibitors wortmannin, U0126, SB203580, and SP600125, respectively. Also, phosphor‐AKT was reduced by ERK1/2 and P38 inhibitors. Ephrin A1‐induced proliferation and migration of pLE cells was also blocked by those inhibitors. Collectively, these results suggest that ephrin A1 enhances interactions between porcine blastocysts and endometrial luminal epithelial cells by activating PI3K and MAPK signal transduction pathways. J. Cell. Physiol. 232: 1527–1538, 2017. © 2016 Wiley Periodicals, Inc.
Evaluation of brewer's spent grain as a substrate for production of hydrolytic enzymes by keratinolytic bacteria
Authors: Łaba Wojciech , Piegza Michał , Kawa‐Rygielska Joanna
Published: October 2016

BACKGROUND

Brewer's spent grain (BSG) is the most abundant by‐product of the brewery industry. The current massive output of BSG requires novel methods of bioconversion into added‐value products. Its composition and high biological value, i.e. high protein content, allows for various biotechnological applications.

RESULTS

Here, BSG was used as a substrate for submerged cultivation of keratinolytic bacteria, Bacillus cereus PCM 2849 and B. subtilis PCM 2850. The strains biosynthesized proteases to decompose proteins within the substrate and amylases to degrade residual starch. Enzymes degrading structural polysaccharides were also present. Bacillus cereus produced multiple proteases with high activity, predominantly with molecular weight (mw) >70 kDa, depending on the presence of minerals. Bacillus subtilis biosynthesised proteases of wide mw range, independently of the mineral components. Crude culture fluids of both bacteria exhibited proteolytic activity on a variety of proteins, including keratins. Structural deterioration of the BSG in microbial cultures was observed.

CONCLUSION

The BSG was a suitable medium component for the production of bacterial proteases and polysaccharide‐degrading enzymes. Two keratinolytic Bacilli, grown in the presence of BSG utilized residual proteins and biosynthesized proteases exhibiting keratinolytic activity. Bacillus cereus dominated in terms of protease production, while B. subtilis presented higher production of amylases, cellulases and xylanases. © 2016 Society of Chemical Industry
Kinetic model selection to describe the growth curve of Arthrospira (Spirulina) maxima in autotrophic cultures
Authors: Escalante Froylán ME , Reyna‐Angeles Karen Alejandra , Villafaña‐Rojas Juan , Aguilar‐Garnica Efrén
Published: October 2016

BACKGROUND

Currently, microbial products are gaining worldwide importance. Arthrospira (Spirulina) maxima is one of the most widely studied microorganisms whose industrial importance is due to its ability to accumulate high amounts of good‐quality proteins; as a consequence, research efforts of many health food and aquaculture industries are focused on the development of tools to optimize the commercial exploitation of this microalgae (cyanobacteria). Kinetic models can appropriately describe the patterns of growth and product formation, which are necessary for any biotechnological process using microorganisms. Some primary, secondary or even more complex kinetic models have been used to depict the growth of microalgae, but to the best of our knowledge, little has been done to choose the most appropriate one.

RESULTS

The present contribution addresses the selection of a kinetic model to describe the growth curve of Arthrospira maxima by considering Akaike's weights as a measure that simultaneously considers the goodness‐of‐fit and the complexity of the model (i.e. number of parameters). Specifically, Haldane‐based, Monod‐based, and logistic kinetic models are considered as candidates to describe the growth of A. maxima under autotrophic conditions.

CONCLUSION

The logistic model, which is the most parsimonious, should be selected to describe the growth of A. maxima within a photobioreactor either in continuous light operation or in dark/light cycles at several light intensities. The selection of this model will allow implementation of simpler monitoring, control, and optimization schemes. © 2016 Society of Chemical Industry
Ex vivo detection and characterization of remineralized carious dentin, by nanoindentation and single point Raman spectroscopy, after amalgam restoration
Authors: Toledano Manuel , Osorio Estrella , Aguilera Fátima S. , Cabello Inmaculada , Toledano‐Osorio Manuel , Osorio Raquel
Published: October 2016

The aim of this study was to assess the mechanical and chemical performance of sound and caries‐affected dentin, after Zn‐free versus containing amalgam restorations placement and thermocycling. Dentin surfaces were studied by Atomic Force Microscopy analysis for surface morphological characterization (including fibril diameter assessment), nano‐indentation (to measure nano‐hardness‐Hi and modulus of Young‐Ei), and single point Raman spectroscopy for chemical analysis. Measurements were performed before amalgam placement, after amalgam removal, and after 3 months of thermocycling (100 000 cy/5 °C and 55 °C). Restorations increased both Hi and Ei at intertubular dentin of caries‐affected dentin. The highest values of Hi were achieved at intertubular dentin after restoring with Zn‐containing amalgams. Remineralization of dentin was attributed to the increase of both amorphous and crystalline new mineral, as lower degrees of crystal imperfections in junction with crystal disorders, and improvement in structural stability of collagen were found. Higher presence of minerals was also confirmed after the decrease of fluoridated apatite. The increase of bands assigned to vibration of carbonate calcium phosphate contributed to a decrease of crystallinity. Copyright © 2016 John Wiley & Sons, Ltd.
Revisiting the gastric pull‐up for pharyngoesophageal reconstruction: A systematic review and meta‐analysis of mortality and morbidity
Authors: Butskiy Oleksandr , Rahmanian Ronak , White Richard A. , Durham Scott , Anderson Donald W. , Prisman Eitan
Published: October 2016

Gastric pull‐up (GPU) is among the oldest techniques for reconstructing the pharyngoesophageal junction following cancer resection. This review examines morbidity and mortality rates following GPU pharyngoesophageal junction reconstruction from 1959 until present: 77 studies, 2,705 patients. The odds of mortality, anastomotic complications, and other complications decreased by 37.2% (95%CI = 28.0–45.3%; P < 0.0001), 8.0% (95%CI = −2.1 to 17.1%; P = 0.12), 21.0% (95%CI 3.5–35.2%; P = 0.021) per decade respectively. J. Surg. Oncol. 2016;114:907–914. © 2016 Wiley Periodicals, Inc.
Characteristics of tinnitus in adolescents and association with psychoemotional factors
Authors: Kim So Young , Jeon Yung Jin , Lee Jun‐Young , Kim Young Ho
Published: October 2016

Objectives/Hypothesis

The characteristics and underlying mechanisms of tinnitus remain more elusive in the pediatric population than in adults. We investigated the prevalence of tinnitus, its characteristics, and associated factors, with a focus on psychoemotional problems in adolescents.

Study Design

Cross‐sectional study

Methods

In total, 962 adolescents were surveyed for tinnitus and possibly related otologic and socioeconomic factors. The participants completed a visual analog scale (VAS) pertaining to various aspects of tinnitus, as well as the Tinnitus Handicap Inventory, Children's Depression Inventory (CDI), State Anxiety Inventory for Children, Trait Anxiety Inventory for Children (TAIC), Internet Addiction Test, Conners' Abbreviated Parent Rating Scale, and a learning disability score. Characteristics of tinnitus were analyzed, and psychoemotional and other factors were compared between tinnitus and nontinnitus groups.

Results

Approximately one‐third of subjects reported experiencing tinnitus. A family history of tinnitus, subjective hearing loss, dizziness, and CDI and TAIC abnormalities were significantly associated with tinnitus. In the tinnitus‐always group, tinnitus showed significant relationships with subjective hearing loss, bilateral tinnitus, and VAS, CDI, and TAIC scores.

Conclusions

The results suggest that about one‐third of adolescents experience tinnitus, which may be related to psychoemotional factors. In particular, anxiety and depression may be important factors to consider in managing tinnitus in adolescents. Further study of tinnitus in adolescents, including efforts toward diagnosis and management, is needed to determine whether there is a causal relationship with anxiety and depression, and the extent to which adverse outcomes may be associated with these psychoemotional factors.

Level of Evidence

4 Laryngoscope, 127:2113–2119, 2017
PCL–PLLA Semi‐IPN Shape Memory Polymers (SMPs): Degradation and Mechanical Properties
Authors: Woodard Lindsay N. , Page Vanessa M. , Kmetz Kevin T. , Grunlan Melissa A.
Published: October 2016

Thermoresponsive shape memory polymers (SMPs) based on poly(ε‐caprolactone) (PCL) whose shape may be actuated by a transition temperature (T
trans) have shown utility for a variety of biomedical applications. Important to their utility is the ability to modulate mechanical and degradation properties. Thus, in this work, SMPs are formed as semi‐interpenetrating networks (semi‐IPNs) comprised of a cross‐linked PCL diacrylate (PCL‐DA) network and thermoplastic poly(l‐lactic acid) (PLLA). The semi‐IPN uniquely allows for requisite crystallization of both PCL and PLLA. The influence of PLLA (PCL:PLLA wt% ratio) and PCL‐DA molecular weight (n) on film properties are investigated. PCL–PLLA semi‐IPNs are able to achieve enhanced mechanical properties and accelerated rates of degradation.

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3D Lattice Structure Control of Ordered Macroporous Material by Self‐Assembly of Liquid Droplets
Authors: Iwai Yosuke , Uchida Yoshiaki , Yabu Hiroshi , Nishiyama Norikazu
Published: October 2016

Microfluidic devices, which can continuously fabricate single emulsion with monodispersed droplets having a pore diameter of more than 100 μm in large numbers, can be applied to manufacture ordered macroporous films. 3D ordered macroporous films with a diameter of more than 100 μm can be fabricated using ordered arrays of the monodispersed droplets as templates of the macropores, which are self‐assembled in the space between two parallel flat glass plates. As the gap between the glass plates increases, the number of the layer increases. Furthermore, in the case with two or more layers, the lattice structure of the macroporous films also changes due to the confinement effects.

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Solvent‐Dependent Structure Formation in Drying P3HT:PCBM Films Studied by Molecular Dynamics Simulations
Authors: Negi Vikas , Lyulin Alexey , Bobbert Peter
Published: October 2016

Phase separation in the donor‐acceptor blend poly(3‐hexylthiophene‐2,5‐diyl):[6,6]‐phenyl‐C61‐butyric acid methyl ester (P3HT:PCBM) during evaporation of a solvent using coarse‐grained molecular dynamics simulations is studied here. To this end, an equilibrated P3HT:PCBM:solvent mixture is placed in an elongated simulation box, after which solvent molecules are removed at regular time intervals from a region above the film. Three often‐used solvents are considered: chloroform (CFM), chlorobenzene (CLB), and orthodichlorobenzene (oDCB). The coarse‐grained solvent–solvent interaction parameters are tuned to reproduce the atmospheric boiling temperatures, while the PCBM–solvent interaction parameters are tuned to reproduce the PCBM solubilities. Other parameters are taken from the literature. During evaporation, the formation of a crust that is depleted of solvent, in which aggregation of P3HT and PCBM occurs, is observed. In agreement with experiment, the top region of the dry film is rich in PCBM for the cases of CLB and oDCB, and rich in P3HT for the case of CFM, while the very top layer of the film is always rich in P3HT. This vertical separation is ascribed to a competition between the tendency of P3HT to move to the surface due to its low surface energy and the different tendencies of PCBM to be dragged along to the surface by the evaporating solvent depending on its solubility. Also in agreement with experiment, the P3HT–PCBM interface area is larger for CLB and oDCB than for CFM. For CLB and oDCB, an indication for a spinodal P3HT–PCBM decomposition starting from the top and bottom surface is found, whereas for CFM the phase separation appears to be initiated in the bulk of the film.

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Evaluation and comparison of tools for diagnosing problematic prescription opioid use among chronic pain patients
Authors: Kovatch Merav , Feingold Daniel , Elkana Odelia , Lev‐Ran Shaul
Published: October 2016

Prescription opioid medications are commonly used for the treatment of chronic pain. Assessments of problematic opioid use among pain patients are inconsistent across studies, partially due to differences between various measures. Therefore, the most appropriate measure to use is often unclear. In this study we assessed problematic opioid use in a sample of 551 individuals receiving treatment for chronic pain, using three questionnaires: the Alcohol Use Disorder and Associated Disabilities Interview Schedule – Fourth Edition (AUDADIS‐IV), the Current Opioid Misuse Measure (COMM) questionnaire and Portenoy's criteria (PC). These questionnaires yielded discordant positive rates of problematic use: 52.6%, 28.7%, and 17.1%, respectively, which did not change substantially when excluding AUDADIS‐IV criteria of physical symptoms of tolerance and withdrawal. Although these three questionnaires share some statistically correlated content‐based congruent questions, positive response rates to them were significantly different based on construction features, including questionnaires' referred time‐frame, wording of questions and response alternatives. The findings of the present study illustrate strengths and limitations of the AUDADIS‐IV, COMM and PC in diagnosing problematic opioid use in a population of adults suffering from chronic pain, and highlight the importance of recognizing and addressing specific questionnaire and question‐related differences when identifying problematic opioid use in this population.
Experimental and CFD Study of a Vertically Stirred Tubular Reactor Designed for Suspension Polymerization Reactions
Authors: Nogueira André L. , Quadri Marintho B. , Machado Ricardo A. F. , Claumann Carlos A.
Published: October 2016

A vertically stirred tubular reactor is designed and studied in this work to perform the styrene batch suspension polymerization. Computational fluid dynamic techniques are applied to acquire information regarding the heat transfer and fluid flow behavior along the reactor. The simulated findings are used to support the experimental results (particle size distribution—PSD) obtained by varying the stirring system configuration, stabilizing agent concentration, and system holdup (styrene/water ratio v/v). According to the results, an efficient temperature control is attained due to the tubular geometry of the equipment. In addition, the PSD broadens by increasing the size of the shaft and the number of impellers installed along the reactor. An evaluation of the particle sedimentation throughout the reaction demonstrates that the PSD and the stirring rate play an important role in the sedimentation kinetics. Such findings demonstrate the potential of the proposed reactor to be explored in order to perform suspension polymerizations semicontinuously or continuously by applying suitable operation strategies.

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Bulk Free‐Radical Copolymerization of n‐Butyl Acrylate and n‐Butyl Methacrylate: Reactivity Ratio Estimation
Authors: Ren Shanshan , Hinojosa‐Castellanos Laura , Zhang Lisha , Dubé Marc A.
Published: October 2016

The reactivity ratios for the bulk free‐radical copolymerization of n‐butyl acrylate (BA)/n‐butyl methacrylate (BMA) are estimated at 80 °C. By performing a series of low conversion runs including replicate runs, the reactivity ratios are estimated as rBA = 0.460 and rBMA = 2.008. Runs to high conversions are then conducted at three different feed compositions (fBMA = 0.2, 0.5, and 0.8) to validate the reactivity ratios. The composition data from the high conversion experiments show good agreement with the estimated reactivity ratios in the integrated form of the Mayo–Lewis model. The molecular weight, gel content, and glass transition temperature of BA/BMA copolymers are also determined.

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Resting‐state functional MRI as a tool for evaluating brain hemodynamic responsiveness to external stimuli in rats
Authors: Paasonen Jaakko , Salo Raimo A. , Huttunen Joanna K. , Gröhn Olli
Published: October 2016

Purpose

Anesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting‐state fMRI (rs‐fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs‐fMRI, such as functional connectivity (FC), are also directly related to blood‐oxygen‐level–dependent (BOLD) responses.

Methods

A simple rs‐fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (α‐chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1‐hour interval. Supplementary forepaw stimulation experiments were also conducted.

Results

Under thiobutabarbital anesthesia, FC was clearly coupled with nicotine‐induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs‐fMRI protocol revealed significant temporal changes in the FC in the α‐chloralose, thiobutabarbital, and urethane groups.

Conclusion

Our results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136–1146, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Urinary incontinence, but not fecal incontinence, is a risk factor for admission to aged residential care of older persons in New Zealand
Authors: Schluter Philip J. , Ward Charlotte , Arnold Edwin P. , Scrase Richard , Jamieson Hamish A.
Published: October 2016

Aims

To determine if urinary incontinence (UI) and fecal incontinence (FI) were independent risk factors for aged resident care (ARC) admissions for older people, after controlling for confounders and applying apposite statistical methods.

Methods

Since 2012, all community care recipients in New Zealand have undergone a standardized needs assessment using the Home Care International Residential Assessment Instrument (interRAI‐HC). The interRAI‐HC instrument elicits information on 236 questions over 20 domains, including UI and FI frequency within the last 3 days. Those aged 65+ years with an interRAI‐HC assessment between July 1, 2012 and May 31, 2014 were matched to national mortality and ARC databases, and competing‐risk regression models applied to those without collection devices or indwelling catheters who were admitted to ARC or alive 30+ days after their interRAI‐HC assessment.

Results

Overall, 32 285 people were eligible, with average age of 82.1 years (range 65, 105 years) of whom 20 627 (63.9%) were female. UI and FI was reported by 36.4% and 12.9% of people, respectively. By June 30, 2014, 5993 (18.6%) had an ARC admission and 5443 (16.9%) had died before any such admission. In the multivariable analysis, the subhazard ratio (SHR) for ARC admission was significant for UI (SHR = 1.11, 95%CI: 1.05, 1.18) but not for FI (SHR = 1.07, 95%CI: 0.99, 1.16).

Conclusions

UI is a common, independent risk factor for ARC admissions. Identifying the extent of incontinence and its impact on ARC admissions is the first vital step in addressing the burgeoning need for better community continence services.
Redox‐regulation of activator protein 1 family members in blood cancer cell lines exposed to cold physical plasma‐treated medium
Authors: Schmidt Anke , Rödder Katrin , Hasse Sybille , Masur Kai , Toups Lena , Lillig Christopher H. , von Woedtke Thomas , Wende Kristian , Bekeschus Sander
Published: October 2016

Targeting cancer cells with cold physical plasma emerged as a promising application in plasma medicine. To understand its mode of action with regard to cellular redox‐regulation, two leukemia cell lines (Jurkat and THP‐1 cells) were plasma‐treated and their gene expression was compared. Transcriptomics revealed strikingly similar expression levels of activator protein 1 family members, and of a particular set of genes associated with apoptosis, DNA repair, and antioxidant defense. Interestingly, important constitutively expressed antioxidant transcripts were differently expressed in both cell types which suggest them to be crucial for the Jurkat's high and the THP‐1 cells’ low sensitivity to plasma. Utilizing these targets as biological read outs may help rendering plasmas more effective against different types of cancers.
Pulmonary hypertension in childhood interstitial lung disease: A systematic review of the literature
Authors: Bromley Susan , Vizcaya David
Published: October 2016

Childhood interstitial lung disease (chILD) comprises a wide heterogeneous group of rare parenchymal lung disorders associated with substantial morbidity and mortality. Pulmonary hypertension is a common comorbidity in adults with interstitial lung disease (ILD) and associated with poor survival. We aimed to systematically review the literature regarding the occurrence of pulmonary hypertension (PH) in chILD, its effect on prognosis and healthcare use, and its treatment in clinical practice. Searches of PubMed and EMBASE databases (up to February 2016), and American Thoracic Society conference abstracts (2009–2015) were conducted using relevant keywords. References from selected articles and review papers were scanned to identify further relevant articles. A total of 20 articles were included; estimates of PH in chILD ranged from 1% to 64% with estimates among specific chILD entities ranging from 0% to 43%. Comparisons between studies were limited by differences in the study populations, including the size, age range, and heterogeneous composition of the ILD case series in terms of the nature and severity of the clinical entities, and also the methods used to diagnose PH. Three studies found that among patients with chILD, those with PH had a significantly higher risk (up to sevenfold) of death compared with those without PH. Information on the treatment of pulmonary hypertension in chILD or the effect of PH on healthcare use was not available. Data on the use and effectiveness of treatments for pulmonary hypertension in chILD are required to address this area of unmet need. Pediatr Pulmonol. 2017;52:689–698. © 2016 Wiley Periodicals, Inc.
Human CaaX protease ZMPSTE24 expressed in yeast: Structure and inhibition by HIV protease inhibitors
Authors: Clark Kathleen M. , Jenkins Jermaine L. , Fedoriw Nadia , Dumont Mark E.
Published: October 2016

The function and localization of proteins and peptides containing C‐terminal “CaaX” (Cys‐aliphatic‐aliphatic‐anything) sequence motifs are modulated by post‐translational attachment of isoprenyl groups to the cysteine sulfhydryl, followed by proteolytic cleavage of the aaX amino acids. The zinc metalloprotease ZMPSTE24 is one of two enzymes known to catalyze this cleavage. The only identified target of mammalian ZMPSTE24 is prelamin A, the precursor to the nuclear scaffold protein lamin A. ZMPSTE24 also cleaves prelamin A at a second site 15 residues upstream from the CaaX site. Mutations in ZMPSTE24 result in premature‐aging diseases and inhibition of ZMPSTE24 activity has been reported to be an off‐target effect of HIV protease inhibitors. We report here the expression (in yeast), purification, and crystallization of human ZMPSTE24 allowing determination of the structure to 2.0 Å resolution. Compared to previous lower resolution structures, the enhanced resolution provides: (1) a detailed view of the active site of ZMPSTE24, including water coordinating the catalytic zinc; (2) enhanced visualization of fenestrations providing access from the exterior to the interior cavity of the protein; (3) a view of the C‐terminus extending away from the main body of the protein; (4) localization of ordered lipid and detergent molecules at internal and external surfaces and also projecting through fenestrations; (5) identification of water molecules associated with the surface of the internal cavity. We also used a fluorogenic assay of the activity of purified ZMPSTE24 to demonstrate that HIV protease inhibitors directly inhibit the human enzyme in a manner indicative of a competitive mechanism.