bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnolol Attenuates Concanavalin A‐induced Hepatic Fibrosis, Inhibits CD4+ T Helper 17 (Th17) Cell Differentiation and Suppresses Hepatic Stellate Cell Activation: Blockade of Smad3/Smad4 Signalling
Authors: Zhang Hongjun , Ju Baoling , Zhang Xiaoli , Zhu Yanfei , Nie Ying , Xu Yuanhong , Lei Qiuxia
Published: December 2016

Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti‐inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune‐related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo. In response to ConA stimulation, the CD4+ T cells preferred to polarizing towards CD4+ T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA‐treated liver in addition to suppressing interleukin (IL)‐17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α‐SMA) and desmin. More transforming growth factor (TGF)‐β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro, the recombinant IL‐17A plus TGF‐β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up‐regulated phospho‐Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell‐mediated fibrosis.
Permanence can be Defended
Authors: McGee Andrew , Gardiner Dale
Published: December 2016

In donation after the circulatory‐respiratory determination of death (DCDD), the dead donor rule requires that the donor be dead before organ procurement can proceed. Under the relevant limb of the Uniform Determination of Death Act 1981 (USA), a person is dead when the cessation of circulatory‐respiratory function is ‘irreversible’. Critics of current practice in DCDD have argued that the donor is not dead at the time organs are procured, and so the procurement of organs from these donors violates the dead donor rule. We offer a new argument here in defence of current DCDD practice, and, in particular, of the interpretation of the requirement of ‘irreversibility’ as permanence.
Synthesis and biological evaluation of N‐acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors
Authors: Daśko Mateusz , Rachon Janusz , Masłyk Maciej , Kubiński Konrad , Demkowicz Sebastian
Published: December 2016

Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un‐sulfated forms and promotes the growth of various hormone‐dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid‐sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N‐acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4‐(2‐perfluoroundecanoylaminoethyl)‐phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18 μm (IC50 value of 2.13 μm for coumarin‐7‐O‐sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.
Practitioners' perceptions and decision‐making regarding child sexual exploitation – a qualitative vignette study
Authors: Reisel Alma
Published: December 2016

There has been intense controversy about the appropriate response to child sexual exploitation, with debates in the UK particularly hinging on the meaning of consent and coercion. For professionals with a duty to safeguard young people from child sexual exploitation, a key site of tension is how to avoid limiting young people's experience of agency without placing them at risk. Drawing on new qualitative research findings from a vignette study designed to trace professional perception and decision‐making, this paper argues that practitioners' perceptions regarding what counts as consent are refracted through conceptions of age and choice. However, many initial perceptions of agency and its links to age were modified through the interview process. This has implications for how supervision should operate. These topics raise issues of the need for practitioners to have nuanced conceptions of consent in the context of manipulation.
SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1‐mutated patient's management
Authors: Colson C. , Aubry E. , Cartigny M. , Rémy A.‐A. , Franquet H. , Leroy X. , Kéchid G. , Lefèvre C. , Besson R. , Cools M. , Spinoit A.F. , Sultan C. , Manouvrier S. , Philibert P. , Ghoumid J.
Published: December 2016

Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non‐steroidogenic tissues. NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non‐sense NR5A1 mutation in a 46,XY‐DSD with polysplenia female proband and her father, who had hypospadias and asplenia.
The Specificity of Sound Symbolic Correspondences in Spoken Language
Authors: Tzeng Christina Y. , Nygaard Lynne C. , Namy Laura L.
Published: December 2016

Although language has long been regarded as a primarily arbitrary system, sound symbolism, or non‐arbitrary correspondences between the sound of a word and its meaning, also exists in natural language. Previous research suggests that listeners are sensitive to sound symbolism. However, little is known about the specificity of these mappings. This study investigated whether sound symbolic properties correspond to specific meanings, or whether these properties generalize across semantic dimensions. In three experiments, native English‐speaking adults heard sound symbolic foreign words for dimensional adjective pairs (big/small, round/pointy, fast/slow, moving/still) and for each foreign word, selected a translation among English antonyms that either matched or mismatched with the correct meaning dimension. Listeners agreed more reliably on the English translation for matched relative to mismatched dimensions, though reliable cross‐dimensional mappings did occur. These findings suggest that although sound symbolic properties generalize to meanings that may share overlapping semantic features, sound symbolic mappings offer semantic specificity.
Top‐down control of species distributions: feral cats driving the regional extinction of a threatened rodent in northern Australia
Authors: Davies Hugh F. , McCarthy Michael A. , Firth Ronald S. C. , Woinarski John C. Z. , Gillespie Graeme R. , Andersen Alan N. , Geyle Hayley M. , Nicholson Emily , Murphy Brett P.
Published: December 2016

Aim

To investigate whether feral cats influence the distribution of Australia's largest remnant population of the threatened brush‐tailed rabbit‐rat Conilurus penicillatus and examine whether they influenced the extinction probability of C. penicillatus over a 15‐year period (2000–2015).

Location

Melville Island, northern Australia.

Methods

In 2015, small mammal surveys were conducted at 88 sites across Melville Island, 86 of which had previously been surveyed in 2000–2002. We used single‐season occupancy models to investigate correlates of the current distribution of C. penicillatus and dynamic occupancy models to investigate correlates of C. penicillatus local extinction.

Results

Our results show that C. penicillatus, which once occurred more widely across the island, is now restricted to parts of the island where feral cats are rarely detected and shrub density is high. Our results suggest that feral cats are driving C. penicillatus towards extinction on Melville Island, and hence have likely been a significant driver in the decline of this species in northern Australia more broadly. The impact of feral cats appears to be mitigated by vegetation structure.

Main conclusions

The ongoing development and implementation of methods to effectively reduce feral cat densities, coupled with the management of landscape processes to maintain shrub density, through fire management and the removal of large exotic herbivores, will contribute substantially to conserving this threatened species. This study demonstrates that the distribution of species can be strongly influenced by top‐down factors such as predation, thereby highlighting the importance of including biotic interactions when investigating the distribution of predation‐susceptible species.
“Do as I Do and Not as I Say”: Exploring Price‐Oriented Maverick Buying During Supplier Selection
Authors: Scott Marc A. , Burke Gerard , Szmerekovsky Joseph
Published: December 2016

This article empirically examines the occurrence of price‐oriented maverick buying (MB) during supplier selection, in a direct purchasing process context. Drawing on agency theory, maverick buying, and total cost of ownership (TCO) literature, the statistically significant existence of price‐oriented MB is investigated and the purchasing manager (PM)‐related factors that influence such noncompliant behavior are determined. A discrete choice experiment is designed to simulate a TCO‐based supplier selection process in which an established purchasing framework agreement stipulates PMs not necessarily be price‐oriented (i.e., select suppliers primarily based on lowest price), and then models PM choice behavior in the supplier selection process (SSP), utilizing a conditional logit model (CLM) to determine PM compliance to the established purchasing framework agreement and identify if price‐oriented MB exists. Statistical tests utilizing comprehensive primary and secondary data are then conducted to determine if correlational relationships exist between PM‐related factors and PM price‐orientation. Results indicate that three PM‐related factors bear a significant correlational relationship to PM price‐orientation.
Technical review of endoscopic ultrasonography‐guided gastroenterostomy in 2017
Authors: Itoi Takao , Baron Todd H. , Khashab Mouen A. , Tsuchiya Takayoshi , Irani Shayan , Dhir Vinay , Bun Teoh Anthony Yuen
Published: December 2016

Gastric outlet obstruction (GOO) can be caused by benign and malignant diseases and often leads to a reduction in patient quality of life. Lately, endoscopic ultrasonography (EUS)‐guided gastroenterostomy (EUS‐GE) has emerged. At the present time, there are three types of EUS‐GE using lumen‐apposing biflanged metal stents (LAMS): (i) direct EUS‐GE; (ii) assisted EUS‐GE using retrieval/dilating balloon, single balloon overtube, nasobiliary drain and ultraslim endoscope; and (iii) EUS‐guided double‐balloon‐occluded gastrojejunostomy bypass (EPASS). Overall technical success rate is approximately 90% regardless of technique used, although this is based on two retrospective studies only. In the EPASS procedure, the success rate of the one‐step procedure was higher than that of the two‐step procedure (100% vs 82%). Clinical success was almost uniform when stent placement was technically successful. Although there have been no‐stent induced procedural deaths, adverse events were seen in several cases. One technically failed case carried out using balloon‐assisted EUS‐GE was converted to laparoscopic gastrojejunostomy. Two failed cases in EPASS procedure improved with conservative treatment. In the present review, we show the feasibility and outcomes using novel EUS‐GE using LAMS. Clinical prospective trials with comparison to luminal enteral stents and surgical GE are warranted.
Taxing behavioral control diminishes sharing and costly punishment in childhood
Authors: Steinbeis Nikolaus
Published: December 2016

Instances of altruism in children are well documented. However, the underlying mechanisms of such altruistic behavior are still under considerable debate. While some claim that altruistic acts occur automatically and spontaneously, others argue that they require behavioral control. This study focuses on the mechanisms that give rise to prosocial decisions such as sharing and costly punishment. In two studies it is shown in 124 children aged 6–9 years that behavioral control plays a critical role for both prosocial decisions and costly punishment. Specifically, the studies assess the influence of taxing aspects of self‐regulation, such as behavioral control (Study 1) and emotion regulation (Study 2) on subsequent decisions in a Dictator and an Ultimatum Game. Further, children's perception of fairness norms and emotional experience were measured. Taxing children's behavioral control prior to making their decisions reduced sharing and costly punishment of unfair offers, without changing perception of fairness norms or the emotional experience. Conversely, taxing children's emotion regulation prior to making their decisions only led to increased experience of anger at seeing unfair offers, but left sharing, costly punishment and the perception of fairness norms unchanged. These findings stress the critical role of behavioral control in prosocial giving and costly punishment in childhood.
Adults blink more deeply: a comparative study of the attentional blink across different age groups
Authors: Russo Natalie , Kates Wendy R. , Shea Nicole , LeBlanc Megan , Wyble Bradley
Published: December 2016

The attentional blink (AB) is thought to help the visual system parse and categorize rapidly changing information by segmenting it into temporal chunks, and is elicited using Rapid Serial Visual Presentation. It is reflected in a decrease in accuracy at detecting the second of two targets presented within 200–500 ms of the first, and its development appears to be protracted on tasks that require set‐shifting. Here, younger (M = 8.5 years) and older (M = 12.8 years) children and adults (M = 19.13 years) completed a simple AB task with no set‐shift requirement in which participants detected two letters in a stream of numbers presented at a rate of 135 ms/item. In addition to assessing the developmental course of the AB on this simple task, we also assessed temporal order errors, or swaps. The AB and its associated characteristics are present in both groups but developmental differences were noted in the depth of the AB, and the presence or absence of lag‐1 sparing. These developmental changes were explained by changes in a single parameter, inhibition, using the eTST model, which suggests that the AB is an adaptive function of the visual system.
Clinical presentation and echocardiographic characteristics of Uhl's anomaly
Authors: Mihos Christos G. , Larrauri‐Reyes Maiteder , Yucel Evin , Santana Orlando
Published: December 2016

Uhl's anomaly is a rare cardiac malformation that results in partial or complete absence of the right ventricular myocardium. It most commonly presents in prenatal or newborn infants; however, it may also be found in some adults as advanced right‐sided heart failure. Differential diagnoses include arrhythmogenic right ventricular dysplasia and Ebstein's anomaly. Herein, we describe the clinical presentation of Uhl's anomaly in a previously undiagnosed middle‐aged adult, and review the echocardiographic criteria used to diagnose and differentiate this rare, albeit important, myocardial disorder.
Evaluation of the brachial artery endothelial function in chronic alcohol consumption among males by high‐frequency ultrasonography
Authors: Luo Runlan , Shen Jiaqi , Zhou Qiao , Liu Yue , Li Guangsen
Published: December 2016

Objective

There is evidence suggesting that different volumes of chronic alcohol consumption have different effects on the endothelium. Therefore, using high‐frequency ultrasonography, we evaluate the effects of the different volume and duration of alcohol intake on brachial artery endothelial function in chronic drinkers.

Methods

Ninety‐two male chronic episodic alcoholics were grouped by alcohol intake amount and duration: mild (group B, n=30); ≤90 mg ethanol daily, 3–5 days/wk for 5–8 years; moderate (group C, n=30); 90–150 mg ethanol daily, 3–5 days/wk for 9–20 years; and severe (group D, n=32); ≥150 mg ethanol daily, 6–7 days/wk for more than 10 years. Thirty male nondrinkers were recruited as the control group A. High‐frequency ultrasonography was used to measure brachial artery diameter during rest, during reactive hyperemia and following the administration of nitroglycerin. Endothelial‐dependent brachial artery flow‐mediated dilatation (FMD) and endothelial‐independent brachial artery nitrate‐mediated dilatation (NMD) were calculated.

Results

Flow‐mediated dilatation values for group C and D were significantly lower than those for group A and B (VC=7.63±0.22, VD=5.85±0.23 vs VA=13.35±0.35, VB=12.81±0.36, P<.01). The FMD of group D was significantly lower than that of group C (P<.01). Meanwhile, the NMD of group D was significantly lower than that of the other groups (VD=17.33±6.21 vs VA=25.35±7.42, VB=24.52±8.30, VC=23.35±7.27, P<.01).

Conclusions

Chronic moderate‐to‐heavy alcohol consumption caused endothelial dysfunction, even damaging vascular smooth muscle cells in cases of heavy alcohol consumption, while abstinence and chronic mild alcoholics caused no effect on endothelial function.
Sex‐related differences in abdominal obesity impact on ischemic stroke risk
Authors: Rodríguez‐Campello A. , Jiménez‐Conde J. , Ois Á. , Cuadrado‐Godia E. , Giralt‐Steinhauer E. , Vivanco R. M. , Soriano‐Tárraga C. , Subirana I. , Muñoz D. , Gómez‐González A. , Puig‐Pijoan A. , Roquer J.
Published: December 2016

Background and purpose

The objective of our study was to evaluate sex differences in the impact of weight and abdominal obesity on the risk of ischemic stroke.

Methods

We included 388 patients with ischemic stroke (aged <75 years) assessed consecutively in our hospital and 732 controls matched by age and sex. Vascular risk factors and anthropometric data (waist circumference, weight and height) were recorded. The impact of three anthropometric variables [body mass index (BMI), waist circumference and waist to height ratio] on ischemic stroke risk was calculated. These variables were divided into quartiles for a comprehensive comparison between cases and controls, stratified by sex and adjusted in logistic regression by age and vascular risk factors. Further logistic regression using dummy variables was performed to evaluate the association between BMI‐adjusted abdominal obesity and stroke risk.

Results

Increased BMI was not associated with increased stroke risk overall or in women, but was a protective factor in men [P = 0.03; odds ratio (OR), 0.59 (0.37–0.94)]. Abdominal obesity was a risk factor for stroke in women, in both waist circumference [P < 0.001; OR, 5.79 (3.10–10.85)] and waist to height ratio [P < 0.001; OR, 3.61 (1.99–6.54)] analyses, but was not significant in men. When considered independently of BMI, abdominal obesity was a risk factor in both sexes, but the strength of the association was significantly higher in women.

Conclusions

Increased BMI was related to a lower risk of stroke in men. Abdominal obesity was associated with ischemic stroke in women. The impact of abdominal obesity on stroke risk differs by sex.
Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines
Authors: Lee Keimin , Kim Yoon‐Jung , Choi La‐Mee , Choi Seulki , Nam Hyun , Ko Hui‐Yeon , Chung Gehoon , Lee Jong‐Ho , Jo Su‐Hyun , Lee Gene , Choi Se‐Young , Park Kyungpyo
Published: December 2016

Bradykinin is an important peptide modulator that affects the function of neurons and immune cells. However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells. Both bradykinin B1 and B2 receptors are expressed on human submandibular gland cells, A253 cells, and HSG cells. Bradykinin increased the intracellular Ca2+ concentration ([Ca2+]i) in a concentration‐dependent manner. Interestingly, a specific agonist of the B1 receptor did not have any effect on [Ca2+]i in HSG cells, whereas specific agonists of the B2 receptor had a Ca2+ mobilizing effect. Furthermore, application of the B1 receptor antagonist, R715, did not alter the bradykinin‐mediated increase in cytosolic Ca2+, whereas the B2 receptor antagonist, HOE140, showed a strong inhibitory effect, which implies that bradykinin B2 receptors are functional in modulating the concentration of cytosolic Ca2+. Bradykinin did not affect a carbachol‐induced rise of [Ca2+]i and did not modulate translocation of aquaporin‐5. However, bradykinin did promote the expression of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), implying the role of bradykinin in salivary gland inflammation. These data suggest that bradykinin receptors are involved in Ca2+ signaling in human submandibular gland cells and serve a unique role, which is separate from that of other salivary gland G protein–coupled receptors.
Carbon balances of bioenergy systems using biomass from forests managed with long rotations: bridging the gap between stand and landscape assessments
Authors: Cintas Olivia , Berndes Göran , Cowie Annette L. , Egnell Gustaf , Holmström Hampus , Marland Gregg , Ågren Göran I.
Published: December 2016

Studies report different findings concerning the climate benefits of bioenergy, in part due to varying scope and use of different approaches to define spatial and temporal system boundaries. We quantify carbon balances for bioenergy systems that use biomass from forests managed with long rotations, employing different approaches and boundary conditions. Two approaches to represent landscapes and quantify their carbon balances – expanding vs. constant spatial boundaries – are compared. We show that for a conceptual forest landscape, constructed by combining a series of time‐shifted forest stands, the two approaches sometimes yield different results. We argue that the approach that uses constant spatial boundaries is preferable because it captures all carbon flows in the landscape throughout the accounting period. The approach that uses expanding system boundaries fails to accurately describe the carbon fluxes in the landscape due to incomplete coverage of carbon flows and influence of the stand‐level dynamics, which in turn arise from the way temporal system boundaries are defined on the stand level. Modelling of profit‐driven forest management using location‐specific forest data shows that the implications for carbon balance of management changes across the landscape (which are partly neglected when expanding system boundaries are used) depend on many factors such as forest structure and forest owners’ expectations of market development for bioenergy and other wood products. Assessments should not consider forest‐based bioenergy in isolation but should ideally consider all forest products and how forest management planning as a whole is affected by bioenergy incentives – and how this in turn affects carbon balances in forest landscapes and forest product pools. Due to uncertainties, we modelled several alternative scenarios for forest products markets. We recommend that future work consider alternative scenarios for other critical factors, such as policy options and energy technology pathways.
Sequential analysis of variable markers for predicting outcomes in pediatric patients with acute liver failure
Authors: Uchida Hajime , Sakamoto Seisuke , Fukuda Akinari , Sasaki Kengo , Shigeta Takanobu , Nosaka Shunsuke , Kubota Masaya , Nakazawa Atsuko , Nakagawa Satoshi , Kasahara Mureo
Published: December 2016

Aim

Our aim was to analyze serial changes in the predictive variables and a scoring system retrospectively adapted to evaluate outcomes in pediatric patients with acute liver failure (ALF).

Methods

We retrospectively collected data on 65 patients with ALF. The 65 patients were divided into two groups according to the need for liver transplantation (LT) as follows: LT group (n = 54) and non‐LT group (n = 11). The early determination scoring system of the indications for LT proposed by the Intractable Hepato‐Biliary Diseases Study Group of Japan (JIHBDSG) was used in our study. The area under the receiver operating characteristic curve (AUROC) was calculated for the JIHBDSG score between the LT group and non‐LT group at the time of diagnosis (day 0) and day 3, and day 5 after the diagnosis.

Results

A JIHBDSG score of >3 at day 5 was found to identify the patients requiring LT with 83.7% sensitivity, 81.8% specificity, and 83.3% diagnostic accuracy. Based on a comparison of AUROC values, the JIHBDSG score on day 5 (AUROC 0.91) was higher than that on day 0 (AUROC 0.75) and day 3 (AUROC 0.84).

Conclusion

We showed that a serial analysis of the JIHBDSG score might be useful for predicting outcomes of ALF in pediatric patients who fulfilled the criteria of LT indication in our center. However, further studies are needed to validate our results.
Well‐differentiated invasive breast cancers with equivocal HER2 immunohistochemistry: what is the yield of routine reflex in‐situ hybridization testing?
Authors: Bethune Gillian C , Pettit Alexandra S L , Veldhuijzen van Zanten Daniel , Barnes Penelope J
Published: December 2016

Aims

The 2013 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2 guidelines recommend testing all invasive breast cancers for HER2, typically with immunohistochemistry (IHC) followed by in‐situ hybridization (ISH) when IHC is equivocal. As well‐differentiated breast cancers are rarely HER2‐positive, we assessed the value of routine reflex HER2 ISH testing for this subset of breast cancers.

Methods and results

We collected HER2 IHC 2+ cases and fluorescence in‐situ hybridization (FISH) data from primary breast cancers with well‐differentiated tumour types (grade 1 ductal carcinomas, classic lobular carcinomas, tubular, cribriform and pure mucinous carcinomas) at our centre from 2010 to 2015. Haematoxylin and eosin (H&E) and IHC slides were reviewed to confirm tumour type, grade and IHC score based on ASCO/CAP 2013 guidelines and their recent revisions. Of 4633 invasive carcinomas, 1133 had a well‐differentiated tumour type; 177 of these were HER2 IHC equivocal, three of which were low‐level amplified by FISH (0.3% of all well‐differentiated tumours). One amplified case was classic invasive lobular carcinoma and two were invasive ductal carcinomas, grade 1. One amplified case had chromosome 17 monosomy, and one was rescored as HER2 IHC 1+ upon review. ‘Basolateral’ staining was noted in one amplified case and in 65 of 174 (37.4%) non‐amplified cases. This incomplete membranous staining pattern was observed in the majority of invasive ductal carcinomas that were rescored as 1+ according to the revised 2013 guidelines.

Conclusions

The rate of HER2 amplification among well‐differentiated breast cancers is very low. Basolateral staining in well‐differentiated tumours may be overinterpreted as HER2 IHC 2+, but is rarely associated with HER2 amplification.
Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall
Authors: Chuang Wen‐Yu , Chang Hung , Chang Gwo‐Jyh , Wang Tzu‐Hao , Chang Yu‐Sun , Wang Tong‐Hong , Yeh Chi‐Ju , Ueng Shir‐Hwa , Chien Hui‐Ping , Chang Chiu‐Yueh , Wan Yung‐Liang , Hsueh Chuen
Published: December 2016

Aims

To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma (PMCL), which morphologically mimics diffuse large B cell lymphoma (DLBCL).

Methods and results

We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1‐negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. All cyclin D1‐positive PMCLs tested showed an IGH–CCND1 translocation, whereas one of the four cyclin D1‐negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1‐positive and cyclin D1‐negative PMCLs were similar to those of classical mantle cell lymphoma (MCL) reported previously, confirming the diagnosis. Secondary genetic alterations involved in oncogenic pathways of MCL were observed more frequently in these PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1‐negative PMCLs but in only 40% of the cyclin D1‐positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 translocation in cyclin D1‐negative PMCL.

Conclusion

We demonstrate for the first time that cyclin D1 negativity is surprisingly common in PMCL morphologically mimicking DLBCL, and the use of a simple immunohistochemical algorithm can prevent misclassification and inappropriate treatment.
Development and optimization of fish‐fortified instant noodles using response surface methodology
Authors: Parvathy Unnikrishnan , Bindu Jaganath , Joshy Chalil George
Published: December 2016

Proper and sensible formulation of ingredients in noodles facilitates its calorie cut down thus making it healthier. Fish being a source of cheap and quality protein can serve in the fortification of noodles. Hence, a study was done to formulate and develop fish noodles from Nemipterus japonicus. D‐optimal mixture experimental design with 15 runs was formulated to optimise the different levels of ingredients for noodles. Influence of different ingredients, viz. fish mince, wheat and refined wheat flour (maida) and potato starch, on the physical, cooking and sensory properties of fish noodles was evaluated. The protein content of noodles increased with increase in the fish mince incorporation. Water absorption capacity (WAC) was found to be directly related to the potato starch concentration. Positive correlation was observed between noodle protein content and cooking time. Desirability function scores revealed a noodle combination of 45% fish mince, 47% wheat: maida (1:1) mix and 8% potato starch as optimum.
Edible film incorporated with chitosan and Artemisia annua oil nanoliposomes for inactivation of Escherichia coli O157:H7 on cherry tomato
Authors: Cui Haiying , Yuan Lu , Li Wei , Lin Lin
Published: December 2016

As a natural antibacterial agent, Artemisia annua oil (AAO) exhibited significant antibacterial effect on Escherichia coli O157:H7. However, AAO was volatile and not suitable for surface coatings of fresh produce. Therefore, the edible agar films containing chitosan and AAO liposomes were engineered to overcome the defect. Chitosan was added in the film to enhance the antibacterial activity. Finally, the results showed the mean size of AAO liposomes was about 191.8 nm with a polydispersity index (PDI) of 0.463. The absolute zeta potential value was greater than 30 mV, and the loading efficiency (LE) of 5.0 mg mL−1 AAO liposome was 67.45%. As a proof of concept, the antibacterial activity of the films against E. coli O157:H7 on cherry tomatoes was evaluated. The results indicated that the incorporation of AAO liposomes as a natural antibacterial agent possessed bacteriostatic effect, which had potential for using the developed film as an active packaging.
Enhancement of phenolic compounds content and antioxidant activity of strawberry (Fragaria × ananassa) juice by block freeze concentration technology
Authors: Adorno Wantiê T. , Rezzadori Katia , Arend Giordana D. , Chaves Vitor C. , Reginatto Flávio H. , Di Luccio Marco , Petrus José C.C.
Published: December 2016

The aim of this study was to evaluate the effects of freeze concentration of strawberry juice on content of total phenolic, anthocyanins content and antioxidant activity of the concentrated fluid and the ice obtained. An increase in the values of phenolic content was observed in the concentrate fraction for all the freeze concentration stages (five stages). The process efficiency presented a reduction when compared with the first stage, and however, the average efficiency remained around 65% in all the stages. The concentration of pelargonidin‐3‐O‐glycoside present in samples was increased in all stages. Furthermore, the antioxidant activity of the concentrated fluid of each stage, measured by DPPH and ABTS methods, was significantly higher in comparison with the juice feed. Also, antioxidant activity can be correlated with the content of pelargonidin‐3‐O‐glycoside presented in the strawberry juice. Freeze concentration can be considered a good alternative for improving the antioxidant activity of strawberry juice.
Pancreatic lipase‐related protein 2 is essential for egg hatching in the brown planthopper, Nilaparvata lugens
Authors: Xu L. , Huang H.‐J. , Zhou X. , Liu C.‐W. , Bao Y.‐Y.
Published: December 2016

In this study, we identified a pancreatic lipase‐related protein 2 (PLRP2) gene through searching the transcriptome data of the brown planthopper, Nilaparvata lugens, a monophagous rice pest. PLRP2 mRNAs were first isolated in the human pancreas and play an important role in hydrolysis of galactolipids from the diet. Although homologous PLRP2 genes have been identified in many insect species, their physiological functions remain unknown. The present study for the first time reports the functional role of PLRP2 in an insect species. Differing from mammal PLRP2s, N. lugens PLRP2 was highly expressed in developing oocytes of the ovaries of female adults and little expressed in laid eggs. Suppression of N. lugens PLRP2 expression using RNA interference significantly inhibited egg hatching in rice seedlings, implying that N. lugens PLRP2 was important for oocyte maturation and development. This novel finding will improve our understanding of the reproductive strategies in insects and provides a potential target for future management of crop pests.
Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens
Authors: van Kempen Gijs , Meijvis Sabine , Endeman Henrik , Vlaminckx Bart , Meek Bob , de Jong Ben , Rijkers Ger , Bos Willem Jan
Published: December 2016

Community‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.
Appreciating the work of nurses caring for adults with intellectual disability and mental health issues
Authors: Taua Chris , Neville Christine , Scott Theresa
Published: December 2016

This paper presents findings from a study exploring the nurses’ experience of caring for adults with intellectual disability and mental health issues in inpatient settings. Semi structured interviews were undertaken with 13 nurses from various regions of New Zealand. Methods suggested by an Appreciative Inquiry methodology were used to explore the nurses’ positive experiences of their role. Interviews were transcribed and analysed using open coding and Leximancer (an online data mining tool) analysis to identify dominant themes in the discourse. Analysis revealed themes around ‘Contextualising behaviour’, ‘Communication’, ‘Confidence to care’ and ‘Time’. Participants reflected upon their experiences offering personal interpretations in identifying the aspects of nursing that mattered and that worked. What is shown is that nurses were able to describe a range of creative and adaptive ways of nursing in responding to numerous complex factors they faced in their roles. This suggests a strong foundation on which to advance nursing care in this field.
Sensitivity and specificity of abstraction using gist reasoning measure in adults with traumatic brain injury
Authors: Vas Asha K. , Spence Jeffrey S. , Eschler Benjamin , Chapman Sandra B.
Published: December 2016

Abstraction, a unique aspect of human reasoning, is affected by TBI. Lack of sensitive metrics to characterize abstraction in TBI recovery may impede detection of cognitive deficits and impact daily function. Recent findings found lower performance in abstracting meaning from complex information, referred to as gist reasoning, in adults with TBI. This study extends those findings to (a) compare abstract thinking between adults with TBI and controls on gist reasoning, similarities, and proverbs and (b) examine and compare sensitivity and specificity of abstraction measures. Participants included adults with moderate to severe chronic TBI (n = 30) and controls (n = 40), all between 25 and 55 years. ANOVA examined group differences on abstract thinking performance. A 10‐fold cross‐validation analysis examined sensitivity and specificity of each measure, and all possible combinations of measures. The TBI group performed significantly lower on gist reasoning and similarities. Results demonstrated higher sensitivity of gist reasoning (84.7%) as compared to similarities and proverbs. Specificity of gist reasoning (71.1%) was second highest, with proverbs multiple choice being the highest (85.2%). Combination of measures did not yield significant gains in sensitivity beyond gist reasoning alone. Gist reasoning could provide an additional diagnostic tool to detect impaired abstraction deficits in adults with chronic TBI. Furthermore, gist reasoning performance has implications to guide cognitive training.
Network biogeography of a complex island system: the Aegean Archipelago revisited
Authors: Kougioumoutzis Konstantinos , Valli Anna Thalassini , Georgopoulou Elisavet , Simaiakis Stylianos Michail , Triantis Kostas A. , Trigas Panayiotis
Published: December 2016

Aim

The Aegean Archipelago has been the focal research area for identifying and testing several ecological and evolutionary patterns, yet its biogeographical subdivision has been somewhat overlooked, with the processes driving the assembly of the Aegean island plant communities still remaining largely unclear. To bridge this gap, we identify the biogeographical modules (highly linked subgroups of islands and plant taxa) within the Aegean Archipelago.

Location

The Aegean Archipelago, Greece.

Methods

We used a network approach to detect island biogeographical roles and modules, based on a large and detailed database including 1498 Aegean endemic and subendemic plant taxa distributed on 59 Aegean Islands and five adjacent mainland areas.

Results

The Aegean was divided into six biogeographical modules; the network was significantly modular. None of the modules displayed all four possible biogeographical roles (connectors, module hubs, network hubs, peripherals). Six new biogeographical regions in the Aegean were identified.

Main conclusions

The borders of the six biogeographical regions in the Aegean correspond well to the region's palaeogeographical evolution from the middle Miocene to the end of the Pleistocene. The Central Aegean acts as an ecogeographical filter for the distribution of several plant lineages across the Aegean Sea, while there seems to be a N–S‐oriented biogeographical barrier in the Aegean corresponding to the palaeogeographical situation during the middle Ionian. These biogeographical barriers have been fundamental for both plants and animals.
Pulmonary Vein Stenosis After Second‐Generation Cryoballoon Ablation
Authors: MATSUDA JUNJI , MIYAZAKI SHINSUKE , NAKAMURA HIROAKI , TANIGUCHI HIROSHI , KAJIYAMA TAKATSUGU , HACHIYA HITOSHI , TAKAGI TAKAMITSU , IESAKA YOSHITO , HIRAO KENZO , ISOBE MITSUAKI
Published: December 2016

PV Stenosis After Cryoablation

Background

Pulmonary vein stenosis (PVST) can occur after first‐generation cryoballoon ablation. This study aimed to evaluate the incidence, severity, and characteristics of PVST after second‐generation cryoballoon ablation.

Methods

In total, 103 patients underwent PV isolation of paroxysmal atrial fibrillation using second‐generation cryoballoons with a single big‐balloon 3‐minute freeze technique. Cardiac enhanced multidetector computed tomography (MDCT) was performed both before and a median of 6.0 (4.0–8.0) months after the procedure in all. PVST was classified as follows: minimal (<25%), mild (25–50%), moderate (50–70%), or severe (>70%).

Results

In total, 406 PVs were analyzed. MDCT demonstrated PV stenosis in 10(2.5%) PVs among 8(7.8%) patients. In detail, minimal and mild PVSTs were observed in 6 and 4 PVs, respectively. PVST occurred in the left superior (LSPV), left inferior, and right superior PVs in 6, 1, and 3 PVs, respectively. No stenosis was observed in 15 PVs with active balloon deflations during freezing. All PVSTs had concentric patterns except for 2 PVs with minimal stenosis. Balloon deformities were observed during freezing of 2 PVs with mild stenosis. When the PVST was defined as a >25% decreased diameter, the incidence was 0.98% (4/406; including 3 LSPVs). PVST did not progress further during the follow‐up period.

Conclusions

Although the incidence of PVST was low, it could occur even if a single big‐balloon short freeze technique was applied. The risk of PV stenosis significantly differed among the 4 PVs, and reaching balloon temperatures of −60 °C and active balloon deflations during freezing were not associated with any PV stenosis.
Integrity of the Ganglionated Plexi Is Essential to Parasympathetic Innervation of the Atrioventricular Node by the Right Vagus Nerve
Authors: XHAET OLIVIER , DE ROY LUC , FLORIA MARIANA , DECEUNINCK OLIVIER , BLOMMAERT DOMINIQUE , DORMAL FABIEN , BALLANT ELISABETH , LA MEIR MARK
Published: December 2016

AV Node Innervation by the Right Vagus Nerve

Introduction

Radiofrequency isolation of pulmonary vein can be accompanied by transient sinus bradycardia or atrioventricular nodal (AVN) block, suggesting an influence on vagal cardiac innervation. However, the importance of the atrial fat pads in relation with the vagal innervation of AVN in humans remains largely unknown. The aim of this study was to evaluate the role of ganglionated plexi (GP) in the innervation of the AVN by the right vagus nerve.

Methods and Results

Direct epicardial high‐frequency stimulation (HFS) of the GP (20 patients) and the right vagus nerve (10 patients) was performed before and after fat pad exclusion or destruction in 20 patients undergoing thoracoscopic epicardial ablation for the treatment of persistent AF. Asystole longer than 3 seconds or acute R‐R prolongation over 25% was considered as a positive response to HFS. Prior to the ablation, positive responses to HFS were detected in 3 GPs in 7 patients (35%), 2 GPs in 5 patients (25%), and one GP in 8 patients (40%). After exclusion of the fat pads, all patients had a negative response to HFS. All the patients who exhibited a positive response to right vagus nerve stimulation (n = 10) demonstrated negative responses after the ablation.

Conclusion

The integrity of the GP is essential for the right vagus nerve to exert physiological effects of on AVN in humans.
3‐Dimensional functionalized polycaprolactone‐hyaluronic acid hydrogel constructs for bone tissue engineering
Authors: Hamlet Stephen M. , Vaquette Cedryck , Shah Amit , Hutmacher Dietmar W. , Ivanovski Saso
Published: December 2016

Aim

Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3‐D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)‐hydrogel incorporating bone morphogenetic protein‐7 (BMP‐7).

Materials and Methods

HA‐hydrogels containing human OB ± BMP‐7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP‐7 release in vitro, were assessed by fluorescence staining, RT‐PCR, histological/μ‐CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL‐hydrogel constructs was assessed by μ‐CT and histology.

Results

Osteoblast encapsulation in HA‐hydrogels did not detrimentally effect cell viability, and 3‐D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP‐7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL‐hydrogel constructs containing BMP‐7 formed significantly more volume (mm3) of vascularized bone‐like tissue.

Conclusions

Functionalized mPCL‐HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP‐7 alone.
Association between omega‐3 fatty acids consumption and the risk of type 2 diabetes: A meta‐analysis of cohort studies
Authors: Chen Cai , Yang Yan , Yu Xuefeng , Hu Shuhong , Shao Shiying
Published: December 2016

Aims/Introduction

Epidemiological evidence for the effect of omega‐3 fatty acids on the risk of type 2 diabetes is controversial. A meta‐analysis based on prospective cohorts was carried out to evaluate this issue.

Materials and Methods

Pooled diabetic risk was calculated using a fixed or random effects model. The dose–response relationship was assessed by meta‐regression analysis.

Results

The study showed that consumption of single omega‐3 was associated with an increased risk of type 2 diabetes (relative risk [RR] = 1.45, P < 0.001); whereas the RR for mixed omega‐3 was statistically insignificant. The dose–response curve presented an inverted U‐shape of diabetes risk corresponding to the dose of omega‐3 consumption. Subanalysis showed that omega‐3 was inversely associated with type 2 diabetes risk in Asians (RR = 0.82, P < 0.001); whereas the risk was increased in Westerners (RR = 1.30, P < 0.001). Studies with follow‐up duration ≥16 years and baseline age ≥54 years showed a positive association between type 2 diabetes risk and omega‐3 intake.

Conclusions

The present findings suggest that dosage and composition of omega‐3, ethnicity, trial duration, and age could influence the effect of omega‐3 on type 2 diabetes progression.