bluuebunny/crossref_metadata_2025 huggingface dataset:
The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B
Authors: Papatheodoridis George V. , Idilman Ramazan , Dalekos George N. , Buti Maria , Chi Heng , van Boemmel Florian , Calleja Jose Luis , Sypsa Vana , Goulis John , Manolakopoulos Spilios , Loglio Alessandro , Siakavellas Spyros , Keskın Onur , Gatselis Nikolaos , Hansen Bettina E. , Lehretz Maria , de la Revilla Juan , Savvidou Savvoula , Kourikou Anastasia , Vlachogiannakos Ioannis , Galanis Kostantinos , Yurdaydin Cihan , Berg Thomas , Colombo Massimo , Esteban Rafael , Janssen Harry L.A. , Lampertico Pietro
Published: June 2017

Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long‐term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10‐center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for ≥1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5‐10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5‐10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness ≥12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender‐Hepatitis B score at baseline or year 5 developed HCC. Conclusion: The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially ≥50 years), lower platelets, and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444–1453).
Outcome of patients older than 80 years with diffuse largeB‐cell lymphoma (DLBCL) treated with “standard” immunochemotherapy: A large retrospective study from 4 institutions
Authors: Gobba Stefania , Moccia Alden A. , Gulden‐Sala Wiebke , Conconi Annarita , Diem Stefan , Cascione Luciano , Iacoboni Gloria , Margiotta‐Casaluci Gloria , Aprile von Hohenstaufen Kathrin , Stathis Anastasios , Hitz Felicitas , Pinotti Graziella , Gaidano Gianluca , Zucca Emanuele
Published: June 2017

Little information is available on the very elderly patients with diffuse large B‐cell lymphoma (DLBCL). We performed a retrospective analysis of 281 patients >80 years old with newly diagnosed DLBCL treated in 4 referral institutions in Switzerland and Northern Italy. Primary end points were overall survival, progression‐free survival, and cause‐specific survival. Systemic chemotherapy was given to 239 patients, and 119 of them received rituximab in their initial treatment. At a median follow‐up of 5.5 years, 5‐year progression‐free survival was 26% (95% confidence interval [CI], 20‐32%), 5‐year overall survival was 31% (95% CI, 25‐37%), and 5‐year cause‐specific survival was 48% (95% CI, 41‐55%) for the entire cohort. Rituximab and/or anthracyclines as part of initial treatment were associated with improved outcome. Cause‐specific survival in patients receiving both agents approximated 60% at 5 years. At multivariate analysis, rituximab use maintained a significant prognostic impact after controlling for age, performance status, stage, haemoglobin, and lactate dehydrogenase levels. The International Prognostic Index as well as the more recently proposed revised‐International Prognostic Index and National Comprehensive Cancer Center Network–International Prognostic Index could discriminate patients with significantly different outcomes. Albeit very elderly and potentially frail, there may be a potential for cure in fit DLBCL patients ≥80 years old. Accurate selection of patients able to tolerate proper immunochemotherapy is crucial.
“I'm an ogre so I'm very hungry!” “I'm assistant ogre”: The Social Function of Sibling Imitation in Early Childhood
Authors: Howe Nina , Rosciszewska Joanna , Persram Ryan J.
Published: June 2017

Siblings' imitative behaviors were investigated in 39 middle‐class dyads during six 90‐min home sessions at both Time 1 (M age: older sibling = 4.4 years; younger sibling = 2.4 years) and Time 2 (2 years later). Although younger siblings imitated most often at T1 and T2, older siblings' imitation increased proportionally over time in comparison to younger siblings. Findings highlight the affiliative nature of imitation that occurred during reciprocal play interactions, via positive responses, and the content of the imitation. Finally, age was controlled by comparing first‐born siblings aged 4 at T1 to second‐born siblings aged 4 at T2. Findings demonstrated that sibling imitation had distinct characteristics despite the age match and partner effects. Sibling imitation is a dynamic, interactive social behavior and may be a powerful source of learning for young children.

Highlights

The role of sibling imitation in ongoing play in early childhood is highlighted.

Sibling imitation is a dynamic and affiliative behavior that promotes interaction during play.

Naturalistic observations of sibling imitation document that it is a powerful source of learning for young children.
Depletion of FoxP3+ Tregs improves control of larval Echinococcus multilocularis infection by promoting co‐stimulation and Th1/17 immunity
Authors: Wang Junhua , Müller Stephan , Lin Renyong , Siffert Myriam , Vuitton Dominique A. , Wen Hao , Gottstein Bruno
Published: June 2017

Introduction

The growth potential of the tumor‐like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune‐mediated processes. Previous studies had shown that regulatory T cells (Tregs) become gradually up‐regulated in the course of both chronic human and murine AE. Thus we now tackled the role of FoxP3+ Tregs and FoxP3+‐Treg‐regulated immune response in contributing to the control of this helminthic infection.

Methods

The infection outcome in E. multilocularis‐infected DEREG mice was measured upon determining parasite load (wet weight of parasitic metacestode tissue). Flow cytometry and qRT‐PCR were used to assess Treg, Th17‐, Th1‐, Th2‐type immune responses and antigen presenting cell activation.

Results

We showed that E. multilocularis‐infected DEREG‐mice treated with DT (as compared to infected control DEREG‐mice without DT application) exhibited a significantly lower parasite load, associated with a persisting capacity of co‐stimulation, and an increased Th1/Th17‐polarization.

Conclusions

FoxP3+ Tregs appear as one of the key players in immune regulatory processes favoring (i) metacestode survival by inhibiting the maturation potential of co‐stimulatory activity and (ii) T cell exhaustion (suppressing Th1/Th17‐type immune responses). We showed as well that prospectively, targeting FoxP3+ Tregs could be an option to develop an immunotherapy against AE.
TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain
Authors: González‐Barbosa Emmanuel , Mejía‐García Alejandro , Bautista Elizabeth , Gonzalez Frank J. , Segovia José , Elizondo Guillermo
Published: June 2017

UbcH7 is an ubiquitin‐conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7–parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7–parkin targets alpha‐synuclein and synphilin‐1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin‐1 half‐life. We found that 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin promotes the aryl hydrocarbon receptor binding to Ubch7 gene promoter as well as its transactivation, resulting in an induction of UbcH7 levels in the olfactory bulb, ventral midbrain, hippocampus, striatum, cerebral cortex, brain stem, and medulla oblongata. In parallel, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin promoted synphilin‐1 degradation in an aryl hydrocarbon receptor‐dependent way.
Development of a Cell‐Based Gene Therapy Approach to Selectively Turn Off Bone Formation
Authors: Alvarez‐Urena Pedro , Zhu Banghe , Henslee Gabrielle , Sonnet Corinne , Davis Eleanor , Sevick‐Muraca Eva , Davis Alan , Olmsted‐Davis Elizabeth
Published: June 2017

Cell and gene therapy approaches are safer when they possess a system that enables the therapy to be rapidly halted. Human mesenchymal stem cells were transduced with an adenoviral vector containing the cDNA for bone morphogenetic protein 2 (AdBMP2) to induce bone formation. To make this method safer, a system to quickly kill these virally transduced cells was designed and evaluated. Cells were encapsulated inside poly(ethylene glycol) diacrylate (PEG‐Da) hydrogels that are able to shield the cells from immunological destruction. The system involves an inducible caspase‐9 (iCasp9) activated using a specific chemical inducer of dimerization (CID). Delivering AdBMP2‐transduced human mesenchymal stem cells encapsulated in PEG‐Da hydrogel promoted ectopic ossification in vivo, and the iCasp9 system allowed direct control of the timing of apoptosis of the injected cells. The iCasp9‐CID system enhances the safety of delivering AdBMP2‐transduced cells, making it a more compelling therapeutic for bone repair and spine fusion. J. Cell. Biochem. 118: 3627–3634, 2017. © 2017 Wiley Periodicals, Inc.
Osteogenic commitment and differentiation of human mesenchymal stem cells by low‐intensity pulsed ultrasound stimulation
Authors: Costa Viviana , Carina Valeria , Fontana Simona , De Luca Angela , Monteleone Francesca , Pagani Stefania , Sartori Maria , Setti Stefania , Faldini Cesare , Alessandro Riccardo , Fini Milena , Giavaresi Gianluca
Published: June 2017

Low‐intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm2 LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7, 14, 21 days). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis. LIPUS stimulation (a) regulated the balance between osteoblast commitment and differentiation by specific networks (activations of RhoA/ROCK signaling and upregulation of Ribosome constituent/Protein metabolic process, Glycolysis/Gluconeogenesis, RNA metabolic process/Splicing and Tubulins); (b) allowed the maintenance of a few percentage of osteoblast precursors (21 days CD73+/CD90+: 6%; OCT‐3/4+/NANOG+/SOX2+: 10%); (c) induced the activation of osteogenic specific pathways shown by gene expression (early: ALPL, COL1A1, late: RUNX2, BGLAP, MAPK1/6) and related protein release (COL1a1, OPN, OC), in particular in the presence of osteogenic soluble factors able to mimic bone microenvironment. To summarize, LIPUS might be able to improve the osteogenic commitment of hMSCs in vitro, and, at the same time, enhance their osteogenic differentiation.
Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β‐catenin/TCF1/Runx2 signaling axis
Authors: Hu Lifang , Su Peihong , Yin Chong , Zhang Yan , Li Runzhi , Yan Kun , Chen Zhihao , Li Dijie , Zhang Ge , Wang Liping , Miao Zhiping , Qian Airong , Xian Cory J.
Published: June 2017

Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1‐KD) in MC3T3‐E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms. The results showed that knockdown of MACF1 significantly suppressed mineralization of MC3T3‐E1 cells, down‐regulated the expression of key osteogenic genes alkaline phosphatase (ALP), runt‐related transcription factor 2 (Runx2) and type I collagen α1 (Col Iα1). Knockdown of MACF1 dramatically reduced the nuclear translocation of β‐catenin, decreased the transcriptional activation of T cell factor 1 (TCF1), and down‐regulated the expression of TCF1, lymphoid enhancer‐binding factor 1 (LEF1), and Runx2, a target gene of β‐catenin/TCF1. In addition, MACF1‐KD increased the active level of glycogen synthase kinase‐3β (GSK‐3β), which is a key regulator for β‐catenin signal transduction. Moreover, the reduction of nuclear β‐catenin amount and decreased expression of TCF1 and Runx2 were significantly reversed in MACF1‐KD cells when treated with lithium chloride, an agonist for β‐catenin by inhibiting GSK‐3β activity. Taken together, these findings suggest that knockdown of MACF1 in osteoblastic cells inhibits osteoblast differentiation through suppressing the β‐catenin/TCF1‐Runx2 axis. Thus, a novel role of MACF1 in and a new mechanistic insight of osteoblast differentiation are uncovered.
Study on morphological characteristics and microscopic structure of medicinal organs of Pulsatilla chinensis (Bunge) Regel
Authors: Wang Wen‐Hao , Yang Jun , Peng Hua‐Sheng , Qian Jiang‐Ping
Published: June 2017

Modern clinical studies have found that Pulsatilla radix contains a variety of active ingredients; however, its medicinal parts and microstructure have been controversial. Based on morphological observation and microscopic identification of different structures, we chose Anhui, Henan, Jilin, and Shanxi Province to study Pulsatilla chinensis (Bunge) Regel populations. We specifically addressed different diameters and anatomical structures of different parts of underground organs. We also found that P. chinensis (Bunge) Regel had a “joint point” structure in its underground organ. Above the “joint point” is the rhizome, below the “joint point” is the root. The main medicinal organ is the rhizome. The protective tissues of the endothelial layer of P. chinensis (Bunge) Regel changed in the process of its development. The protective tissues were replaced by epidermis, cortex, endodermis, and phloem. With the secondary growth, the endothelial cells have been radial division. This study showed that morphology and microscopic identification was an important mean of medicinal material identifications, and it had the characteristics of a convenient, fast, and intuitive method to identify the composition and structural characteristics of P. chinensis (Bunge) Regel medicinal parts.
A Facial Synthesis and Anticancer Activity of (Z)‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted Acid
Authors: Pansare Dattatraya N. , Shelke Rohini N. , Shinde Devanand B.
Published: June 2017

In order to explore the anticancer and antimicrobial activity associated with the thiazole framework, we synthesized the new series (Z)‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted acid derivatives 6a–l. All the synthesized compounds were evaluated for anticancer and antimicrobial activity in vitro. Among these, the compounds 6a, 6b, 6c, 6e, 6f, 6g, 6h, 6i, 6j, and 6k showed highest antibacterial and antifungal activity. The compound 6a exhibited significant antibacterial activity against Bacillussubtilis, whereas compound 6j displays significant antifungal activity against fungal strains, that is, A. oryzae. The in vitro anticancer studies revealed that 6e, 6g, 6h, 6k, and 6l are the most active compounds against MCF‐7 and BT‐474 human breast cancer cell lines, which can be regarded as the promising drug candidate for development of anticancer drugs.
An application of CIFAP for predicting the binding affinity of Chk1 inhibitors derived from 2‐aminothiazole‐4‐carboxamide
Authors: Konyar Dilan , Erdas Ozlem , Alpaslan Ferda Nur , Buyukbingol Erdem
Published: June 2017

Investigation of protein‐ligand interactions obtained from experiments has a crucial part in the design of newly discovered and effective drugs. Analyzing the data extracted from known interactions could help scientists to predict the binding affinities of promising ligands before conducting experiments. The objective of this study is to advance the CIFAP (compressed images for affinity prediction) method, which is relevant to a protein‐ligand model, identifying 2D electrostatic potential images by separating the binding site of protein‐ligand complexes and using the images for predicting the computational affinity information represented by pIC50 values. The CIFAP method has 2 phases, namely, data modeling and prediction. In data modeling phase, the separated 3D structure of the binding pocket with the ligand inside is fitted into an electrostatic potential grid box, which is then compressed through 3 orthogonal directions into three 2D images for each protein‐ligand complex. Sequential floating forward selection technique is performed for acquiring prediction patterns from the images. In the prediction phase, support vector regression (SVR) and partial least squares regression are used for testing the quality of the CIFAP method for predicting the binding affinity of 45 CHK1 inhibitors derived from 2‐aminothiazole‐4‐carboxamide. The results show that the CIFAP method using both support vector regression and partial least squares regression is very effective for predicting the binding affinities of CHK1‐ligand complexes with low‐error values and high correlation. As a future work, the results could be improved by working on the pose of the ligands inside the grid.
Development of a H2O2‐sensitive quantum dots‐based fluorescent sandwich ELISA for sensitive detection of bovine β‐lactoglobulin by monoclonal antibody
Authors: He Shengfa , Li Xin , Gao Jinyan , Tong Ping , Chen Hongbing
Published: June 2017

BACKGROUND

Bovine β‐lactoglobulin (BLG) is the major allergen in cows' milk, and the specific epitope plays a key role in food allergy. Developing a method specifically bind to the IgE epitope is necessary for testing BLG and its allergenic residues.

RESULTS

The monoclonal antibody (1G9) specific to the IgE linear epitope for BLG was identified as high affinity and specificity. Based on 1G9, a sensitive fluorescent sandwich enzyme‐linked immunosorbent assay (sELISA) was successfully developed using catalase‐mediated fluorescence quenching of thiolated CdTe quantum dots in the presence of hydrogen peroxide as fluorescent signal output. The fluorescent sELISA showed high sensitivity and specificity, the limit of detection was 0.49 ng mL−1, which was 16‐fold lower than horseradish peroxidase (HRP)‐based sELISA. The linear range for BLG detection were 125–4000 ng mL−1 (r = 0.9939) and 0.48–62.5 ng mL−1 (r = 0.9919). The recoveries and coefficients of variation were 94.25–109.83% and 4.38–20.29%, respectively. Allergenic residues were also detected in hydrolysed infant formulas. The results of fluorescent sELISA showed good performance as HRP‐based sELISA and commercial sELISA kit.

CONCLUSION

This proposed fluorescent sELISA could be employed to detect BLG and its allergenic residues in food with highly sensitivity, reliability, and recovery. © 2017 Society of Chemical Industry
Characteristics improvement of top‐gate self‐aligned amorphous indium gallium zinc oxide thin‐film transistors using a dual‐gate control
Authors: Nag Manoj , De Roose Florian , Myny Kris , Steudel Soeren , Genoe Jan , Groeseneken Guido , Heremans Paul
Published: June 2017

In this work, we have reported dual‐gate amorphous indium gallium zinc oxide thin‐film transistors (a‐IGZO TFTs), where a top‐gate self‐aligned TFTs has a secondary bottom gate and the TFT integration comprises only five mask steps. The electrical characteristics of a‐IGZO TFTs under different gate control are compared. With the enhanced control of the channel with two gates connected together, parameters such as on current (ION), sub‐threshold slope (SS−1), output resistance, and bias‐stress instabilities are improved in comparison with single‐gate control self‐aligned a‐IGZO TFTs. We have also investigated the applicability of the dual‐gate a‐IGZO TFTs in logic circuitry such as 19‐stage ring oscillators.
Dendritic‐cell‐based immunotherapy evokes potent anti‐tumor immune responses in CD105+ human renal cancer stem cells
Authors: Zhang Xiao‐Fei , Weng De‐sheng , Pan Ke , Zhou Zi‐Qi , Pan Qiu‐zhong , Zhao Jing‐Jing , Tang Yan , Jiang Shan‐Shan , Chen Chang‐Long , Li Yong‐Qiang , Zhang Hong‐Xia , Chang Alfred E. , Wicha Max S. , Zeng Yi‐Xin , Li Qiao , Xia Jian‐Chuan
Published: June 2017

Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified “stem‐like” characteristics of CD105+ cells in two human RCC cell lines: A498 and SK‐RC‐39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC‐based immunotherapy for human RCC.
Progress in the synthesis and biological evaluation of lipid A and its derivatives
Authors: Gao Jian , Guo Zhongwu
Published: June 2017

Lipid A is one of the core structures of bacterial lipopolysaccharides (LPSs), and it is mainly responsible for the strong immunostimulatory activities of LPS through interactions with the Toll‐like receptors and other molecules in the human immune system. To obtain structurally homogeneous and well‐defined lipid As and its derivatives in quantities meaningful for various biological studies and applications, their chemical synthesis has become a focal point. This review has provided a survey of significant progresses made in the synthesis of lipid A, and its derivatives that carry diverse saturated and unsaturated lipids, have the phosphate group at its reducing end replaced with a more stable phosphate or carboxyl group, or lack the reducing end phosphate or both phosphate groups, as well as progresses in the synthesis of LPS analogs and other lipid A conjugates. These synthetic molecules have facilitated the elucidation of the structure–activity relationships of lipid A useful for the design and development of lipid A based therapeutics, such as those utilized to treat sepsis, and other medical applications, for example the use of monophosphoryl lipid A as a carrier molecule for the study of fully synthetic self‐adjuvanting conjugate vaccines. These topics are also briefly covered in the current review.
Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment
Authors: Zhou Fubo , Shang Wenting , Yu Xiaoling , Tian Jie
Published: June 2017

Liver cancer is the second leading cause of cancer‐related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican‐3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3‐targeted magnetic resonance imaging, positron emission tomography, and near‐infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti‐GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.
Some inverse problems for the nonlocal heat equation with Caputo fractional derivative
Authors: Torebek Berikbol T. , Tapdigoglu Ramiz
Published: June 2017

A class of inverse problems for restoring the right‐hand side of a fractional heat equation with involution is considered. The results on existence and uniqueness of solutions of these problems are presented.
Inequalities in uptake of prenatal screening according to ethnicity and socio‐economic status in the four largest cities of the Netherlands (2011–2013)
Authors: Posthumus Anke G. , Peters Ingrid A. , Borsboom Gerard J. , Knapen Maarten F. C. M. , Bonsel Gouke J.
Published: June 2017

Objectives

In the Netherlands, all women are claimed to have equal access to prenatal screening (PS). Prior research demonstrated substantial inequalities in PS uptake associated with socioeconomic status (SES) and ethnic background. The suggested pathway was a lack of intention to participate in PS among these subgroups. We studied the background of inequalities in PS participation, challenging intention heterogeneity as the single explanation.

Methods

Multivariable logistic regression analyses of the national PS registry, focusing on the four largest cities in the Netherlands (n = 4578, years 2011–2013), stratified by SES. Outcome measures: (1) any uptake of PS (yes/no) and (2) uptake (one/two tests) for women who intended to participate in two tests. Determinants included intention, ethnicity, practice, and age.

Results

Of non‐Western women, 85.7% were screened versus 89.7% of Western women. Intention was an important explanatory factor in all models. However, after correction for intention, ethnicity remained a significant determinant for differences in uptake. Ethnicity and SES also interacted, indicating that non‐Western women in low SES areas had the lowest uptake (corrected for intention).

Conclusions for Practice

Socioeconomic status and ethnicity related inequalities in PS uptake are only partially explained by intention heterogeneity; other pathways, in particular provider‐related determinants, may play a role. © 2017 John Wiley & Sons, Ltd.
Tunable physicochemical properties of PVA nanocomposite membranes for enhanced pervaporation performance
Authors: Jose Thomasukutty , George Soney C. , Thomas Sabu
Published: June 2017

This study reveals the effect of hydrophilic bentonite nanoclay on the pervaporation separation of azeotropic composition of water and 1,4‐dioxane. The permselectivity of the membrane increased with filler concentration and was selective toward water at minimum filler loading. The intrinsic properties such as membrane permeance and selectivity increased with the concentration of hydrophilic bentonite nanoclay and crosslinked poly(vinyl alcohol) (PVA) with 2 wt% nanoclay membranes showed intrinsic selectivity 443 (532% increment than that of pristine membranes) with water permeance 4,675 gas permeation unit which is significantly higher compared to earlier literature. X‐ray diffraction and Transmission electron microscopy showed the well exfoliated and distributed nanoclay structure in the crosslinked PVA matrix. Interaction of PVA with nanoclay and the hydrophilic character of the membranes were characterized by Fourier transform infrared spectra and contact angle analysis, respectively. Interestingly, in this work the membranes exhibited simultaneous increment in both permeation flux and selectivity with filler loading, rather than the usual inverse trend of flux and selectivity. A predictive model of pervaporation was used to explain the pervaporation behavior and it showed good agreement with experimental results for overall pervaporation performance, preferential sorption of water, and hydrophilic‐hydrophobic nature of the membranes. POLYM. ENG. SCI., 58:849–858, 2018. © 2017 Society of Plastics Engineers
Are People Mindful in Different Ways? Disentangling the Quantity and Quality of Mindfulness in Latent Profiles and Exploring Their Links to Mental Health and Life Effectiveness
Authors: Sahdra Baljinder K. , Ciarrochi Joseph , Parker Philip D. , Basarkod Geetanjali , Bradshaw Emma L. , Baer Ruth
Published: June 2017

We sought to disambiguate the quantitative and qualitative components of mindfulness profiles, examine whether including ‘nonattachment’ as a subcomponent of mindfulness alters the profiles, and evaluate the extent to which the person–centred approach to understanding mindfulness adds predictive power beyond a more parsimonious variable–centred approach. Using data from a nationally representative sample of Americans ( N = 7884; 52% female; Age: M = 47.9, SD = 16), we utilized bifactor exploratory structural equation modelling and latent profile analysis to separate the level and shape of previously identified profiles of mindfulness (Pearson, Lawless, Brown, & Bravo, 2015). Consistent with past research, we identified a judgmentally observing profile and a non–judgmentally aware group, but inconsistent with past research, we did not find profiles that showed high or low levels on all specific aspects of mindfulness. Adding nonattachment did not alter the shape of the profiles. Profile membership was meaningfully related to demographic variables. In models testing the distinctive predictive utility of the profiles, the judgmentally observing profile, compared to the other profiles, showed the highest levels of mental ill–health, but also the highest levels of life satisfaction and effectiveness. We discuss the implications of our study for clinical interventions and understanding the varieties of mindfulness. Copyright © 2017 European Association of Personality Psychology
Different roles of CD4, CD8 and γδ T‐lymphocytes in naive and vaccinated chickens during Salmonella Enteritidis infection
Authors: Sekelova Zuzana , Polansky Ondrej , Stepanova Hana , Fedr Radek , Faldynova Marcela , Rychlik Ivan , Vlasatikova Lenka
Published: June 2017

Lymphocytes represent the key antigen‐specific leukocyte subpopulation. Despite their importance in mounting an immune response, an unbiased description of proteins expressed by chicken lymphocytes has not been presented. In this study, we therefore intravenously infected chickens with Salmonella Enteritidis, sorted CD4, CD8 and γδ T‐lymphocytes from the spleen by flow cytometry and determined the proteome of each population by LC‐MS/MS. CD4 T‐lymphocyte characteristic proteins included ubiquitin SUMO‐like domain and BAR domain containing proteins. CD8 T‐lymphocyte specific proteins were characterized by purine ribonucleoside triphosphate binding and were involved in cell differentiation, cell activation and regulation of programmed cell death. γδ T‐lymphocyte specific proteins exhibited enrichment of small GTPase of Rab type and GTP binding. Following infection, inducible proteins in CD4 lymphocytes included ribosomal proteins and downregulated proteins localized to the lysosome. CD8 T‐lymphocytes induced MCM complex proteins, proteins required for DNA replication and machinery for protein processing in the endoplasmic reticulum. Proteins inducible in γδ T‐lymphocytes belonged to immune system response, oxidative phosphorylation and the spliceosome. In this study, we predicted the likely events in lymphocyte response to systemic bacterial infection and identified proteins which can be used as markers specific for each lymphocyte subpopulation.
Phosphine‐free direct arylation synthesis and self‐assembled nanostructure analysis of poly(3‐hexylselenophene)
Authors: Nakabayashi Kazuhiro , Otsuki Naoto , Mori Hideharu
Published: June 2017

Poly(3‐hexylselenophene)s (P3Hs) with high regioregularity (RR = 92–96%), that is, regioregular poly(3‐hexylselenophene)s (rr‐P3HSs), have been synthesized under the phosphine‐free direct arylation conditions in the presence of PdCl2 as a precatalyst. rr‐P3HS with the high molecular weight (Mn ∼ 10,000) was obtained as a result of screening of direct arylation conditions. Subsequently, the influences of primary structure, molecular weight (Mn = 3900–10,000) and regioregularity (RR = 57–96%), on optical properties and self‐assembled nanostructure of P3HS were investigated. X‐ray diffraction demonstrated that molecular weight, regioregularity, and preparation method of films dominate the crystallization behavior of P3HS. Among these parameters, it was evident that a high degree of regioregularity was the most fundamental contributor to achieve pure crystalline nanostructure. Furthermore, nanoassembly based on pure crystalline nanostructure, such as non‐woven fibrous and bundle‐like spherulitic self‐assembled nanostructures, was successfully prepared in rr‐P3HS, respectively, by appropriate modulation of the aforementioned parameters. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2749–2755
Porous zinc oxide nanocrystalline film deposition by atmospheric pressure plasma: Fabrication and energy band estimation
Authors: Jain Gunisha , Macias‐Montero Manuel , Velusamy Tamilselvan , Maguire Paul , Mariotti Davide
Published: June 2017

Porous ZnO nanocrystalline films have drawn research attention due to improvement in gas sensing, adsorption, photocatalytic, and photovoltaic applications. However, scalable synthesis of porous nanostructures has been a challenge. Here, This paper reports a very easy, fast, and scalable one‐step process for synthesis and deposition of porous ZnO nanocrystalline film by low‐temperature atmospheric pressure plasma. The plasma is generated with radio frequency power using a metallic zinc wire as a precursor. Nanostructures have been synthesized and agglomerate to form a porous film at the substrate. Energy band structure of the deposited film has been investigated to understand the corresponding band alignment, which is relevant to many applications. An in‐depth study of the grown nanostructured ZnO film has been included and characterized by X‐ray diffraction, transmission electron microscopy, X‐ray photoelectron spectroscopy, kelvin probe measurement, ultra‐violet/visible absorption, and photoluminescence.
Testing for bioequivalence of highly variable drugs from TR‐RT crossover designs with heterogeneous residual variances
Authors: Kang Qing , Vahl Christopher I.
Published: June 2017

Traditional bioavailability studies assess average bioequivalence (ABE) between the test (T) and reference (R) products under the crossover design with TR and RT sequences. With highly variable (HV) drugs whose intrasubject coefficient of variation in pharmacokinetic measures is 30% or greater, assertion of ABE becomes difficult due to the large sample sizes needed to achieve adequate power. In 2011, the FDA adopted a more relaxed, yet complex, ABE criterion and supplied a procedure to assess this criterion exclusively under TRR‐RTR‐RRT and TRTR‐RTRT designs. However, designs with more than 2 periods are not always feasible. This present work investigates how to evaluate HV drugs under TR‐RT designs. A mixed model with heterogeneous residual variances is used to fit data from TR‐RT designs. Under the assumption of zero subject‐by‐formulation interaction, this basic model is comparable to the FDA‐recommended model for TRR‐RTR‐RRT and TRTR‐RTRT designs, suggesting the conceptual plausibility of our approach. To overcome the distributional dependency among summary statistics of model parameters, we develop statistical tests via the generalized pivotal quantity (GPQ). A real‐world data example is given to illustrate the utility of the resulting procedures. Our simulation study identifies a GPQ‐based testing procedure that evaluates HV drugs under practical TR‐RT designs with desirable type I error rate and reasonable power. In comparison to the FDA's approach, this GPQ‐based procedure gives similar performance when the product's intersubject standard deviation is low (≤0.4) and is most useful when practical considerations restrict the crossover design to 2 periods.
Mood stabilizers and risperidone
Authors: Lam Y. W. Francis
Published: June 2017

The atypical antipsychotic risperidone is recommended as augmentation therapy to mood stabilizers for the management of patients with bipolar disorder. Antiepileptic drugs, such as lamotrigine, carbamazepine, and valproic acid, also are commonly used for management of various psychiatric disorders, including bipolar disorder.
Decentralized networked control of discrete‐time systems with local networks
Authors: Freirich Dror , Fridman Emilia
Published: June 2017

This paper considers discrete‐time large‐scale networked control systems with multiple local communication networks connecting sensors, controllers, and actuators. The local networks operate asynchronously and independently of each other in the presence of variable sampling intervals, transmission delays, and scheduling protocols (from sensors to controllers). The time‐delay approach that was recently suggested to decentralized stabilization of large‐scale networked systems in the continuous time is extended to
decentralized control in the discrete time. An appropriate Lyapunov‐Krasovskii method is presented that leads to efficient LMI conditions for the exponential stability and l2‐gain analysis of the closed loop large‐scale system. Differences from the continuous‐time results are discussed. A numerical example of decentralized control of 2 coupled cart‐pendulum systems illustrates the efficiency of the results.
Measuring the statistical validity of summary meta‐analysis and meta‐regression results for use in clinical practice
Authors: Willis Brian H. , Riley Richard D.
Published: June 2017

An important question for clinicians appraising a meta‐analysis is: are the findings likely to be valid in their own practice—does the reported effect accurately represent the effect that would occur in their own clinical population? To this end we advance the concept of statistical validity—where the parameter being estimated equals the corresponding parameter for a new independent study. Using a simple (‘leave‐one‐out’) cross‐validation technique, we demonstrate how we may test meta‐analysis estimates for statistical validity using a new validation statistic, Vn, and derive its distribution.

We compare this with the usual approach of investigating heterogeneity in meta‐analyses and demonstrate the link between statistical validity and homogeneity. Using a simulation study, the properties of Vn and the Q statistic are compared for univariate random effects meta‐analysis and a tailored meta‐regression model, where information from the setting (included as model covariates) is used to calibrate the summary estimate to the setting of application. Their properties are found to be similar when there are 50 studies or more, but for fewer studies Vn has greater power but a higher type 1 error rate than Q. The power and type 1 error rate of Vn are also shown to depend on the within‐study variance, between‐study variance, study sample size, and the number of studies in the meta‐analysis. Finally, we apply Vn to two published meta‐analyses and conclude that it usefully augments standard methods when deciding upon the likely validity of summary meta‐analysis estimates in clinical practice. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
Distortion of DNA Origami on Graphene Imaged with Advanced TEM Techniques
Authors: Kabiri Yoones , Ananth Adithya N. , van der Torre Jaco , Katan Allard , Hong Jin‐Yong , Malladi Sairam , Kong Jing , Zandbergen Henny , Dekker Cees
Published: June 2017

While graphene may appear to be the ultimate support membrane for transmission electron microscopy (TEM) imaging of DNA nanostructures, very little is known if it poses an advantage over conventional carbon supports in terms of resolution and contrast. Microscopic investigations are carried out on DNA origami nanoplates that are supported onto freestanding graphene, using advanced TEM techniques, including a new dark‐field technique that is recently developed in our lab. TEM images of stained and unstained DNA origami are presented with high contrast on both graphene and amorphous carbon membranes. On graphene, the images of the origami plates show severe unwanted distortions, where the rectangular shape of the nanoplates is significantly distorted. From a number of comparative control experiments, it is demonstrated that neither staining agents, nor screening ions, nor the level of electron‐beam irradiation cause this distortion. Instead, it is suggested that origami nanoplates are distorted due to hydrophobic interaction of the DNA bases with graphene upon adsorption of the DNA origami nanoplates.
Inside Cover Image, Volume 7, Issue 4
Authors: Ganesan Aravindhan , Coote Michelle L. , Barakat Khaled
Published: June 2017

The inside cover image, by Aravindhan Ganesan et al., is based on the Overview Molecular ‘time‐machines’ to unravel key biological events for drug design, DOI: 10.1002/wcms.1306.

image
Energy scenarios: the value and limits of scenario analysis
Authors: Paltsev Sergey
Published: June 2017

A need for low‐carbon world has added a new challenging dimension for the long‐term energy scenarios development. In addition to the traditional factors like technological progress, demographic, economic, political, and institutional considerations, there is another aspect of the modern energy forecasts related to the coverage, timing, and stringency of policies to mitigate the greenhouse gas emissions and air pollutants. Modern tools for the energy scenario development provide a good basis for the estimates of the required changes in the energy system to achieve certain climate and environmental targets. While the current scenarios show that a move to a low‐carbon energy future requires a drastic change in energy investment and the resulting mix in energy technologies, the exact technology mix, paths to the needed mix, price, and cost projections should be treated with a great degree of caution. The scenarios do not provide exact predictions, but they can be used as a qualitative analysis of decision‐making risks associated with different pathways. If history is any guide, energy scenarios overestimate the extent to which the future will look like the recent past. As future costs and the resulting technology mixes are uncertain, a wise government policy is to target emissions reductions from any source, rather than focus on boosting certain kinds of low‐carbon energy.WIREs Energy Environ2017, 6:e242. doi: 10.1002/wene.242

This article is categorized under:

Energy and Climate > Economics and Policy

Energy and Climate > Systems and Infrastructure

Energy Policy and Planning > Economics and Policy
Gold nanoparticle‐mediated photothermal therapy: applications and opportunities for multimodal cancer treatment
Authors: Riley Rachel S. , Day Emily S.
Published: June 2017

Photothermal therapy (PTT), in which nanoparticles embedded within tumors generate heat in response to exogenously applied laser light, has been well documented as an independent strategy for highly selective cancer treatment. Gold‐based nanoparticles are the main mediators of PTT because they offer: (1) biocompatibility, (2) small diameters that enable tumor penetration upon systemic delivery, (3) simple gold‐thiol bioconjugation chemistry for the attachment of desired molecules, (4) efficient light‐to‐heat conversion, and (5) the ability to be tuned to absorb near‐infrared light, which penetrates tissue more deeply than other wavelengths of light. In addition to acting as a standalone therapy, gold nanoparticle‐mediated PTT has recently been evaluated in combination with other therapies, such as chemotherapy, gene regulation, and immunotherapy, for enhanced anti‐tumor effects. When delivered independently, the therapeutic success of molecular agents is hindered by premature degradation, insufficient tumor delivery, and off‐target toxicity. PTT can overcome these limitations by enhancing tumor‐ or cell‐specific delivery of these agents or by sensitizing cancer cells to these additional therapies. All together, these benefits can enhance the therapeutic success of both PTT and the secondary treatment while lowering the required doses of the individual agents, leading to fewer off‐target effects. Given the benefits of combining gold nanoparticle‐mediated PTT with other treatment strategies, many exciting opportunities for multimodal cancer treatment are emerging that will ultimately lead to improved patient outcomes. WIREs Nanomed Nanobiotechnol 2017, 9:e1449. doi: 10.1002/wnan.1449

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Preserving Relations in Parallel Flow Data Processing
Authors: Čejka Tomáš , Žádník Martin
Published: June 2017

Network monitoring produces high volume of data that must be analyzed ideally in near real-time to support network security operations. It is possible to process the data using Big Data frameworks, however, such approach requires adaptation or complete redesign of processing tools to get the same results. This paper elaborates on a parallel processing based on splitting a stream of flow records. The goal is to create subsets of traffic that contain enough information for parallel anomaly detection. The paper describes a methodology based on so called witnesses that helps to scale up without any need to modify existing algorithms.
SmartDEMAP: A Smart Contract Deployment and Management Platform
Authors: Knecht Markus , Stiller Burkhard
Published: June 2017

Smart contracts on a blockchain behave exactly as specified by their code. To be sure that a smart contract behaves as expected, the end-user has to either analyze its code or trust a potentially anonymous developer or auditor to do so. This approach proposes a smart contract deployment and management platform that can execute development tools and code quality tools in a trusted way and uses this to reduce the trust required into the smart contract developer or auditor. Additionally, such a platform can provide new capabilities for developers aiding them in the creation of smart contracts.