bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal anti‐envelope antibody AP33 protects humanized mice against a patient‐derived hepatitis C virus challenge
Authors: Desombere Isabelle , Fafi‐Kremer Samira , Van Houtte Freya , Pessaux Patrick , Farhoudi Ali , Heydmann Laura , Verhoye Lieven , Cole Sarah , McKeating Jane A. , Leroux‐Roels Geert , Baumert Thomas F. , Patel Arvind H. , Meuleman Philip
Published: December 2015

End‐stage liver disease (ESLD) caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation, the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct‐acting antiviral therapies have reduced efficacy in patients with ESLD and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study, we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct, but overlapping, epitope in the viral E2 glycoprotein to protect humanized mice from a patient‐derived HCV challenge. Their neutralizing activity was assessed using the HCV pseudoparticles and cell‐culture–derived HCV systems expressing multiple patient‐derived envelopes and a human‐liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient‐derived HCV genotype 1b isolate, whereas 3 of 4 AP33‐treated mice were completely protected. In contrast, only one of four 3/11‐treated mice remained HCV‐RNA negative throughout the observation period, whereas the other 3 had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro. Conclusions: Although mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Given that mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and reinfected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition, our data are valuable for the design of a prophylactic vaccine. (Hepatology 2016;63:1120–1134)
Identification of differentially expressed three novel transcript variants of mouse ARNT gene
Authors: Ishqi Hassan Mubarak , Ur Rehman Sayeed , Sarwar Tarique , Husain Mohammed Amir , Tabish Mohammad
Published: December 2015

The aryl hydrocarbon receptor nuclear translocator (ARNT/HIF1‐β) is an obligatory transcriptional partner of the aryl hydrocarbon receptor (AHR) and hypoxia‐inducible factor‐1α (HIF‐1α). It has a basic helix‐loop‐helix domain that belongs to period‐ARNT‐single‐minded (PAS) protein family. PAS proteins act as heterodimeric transcription factors with ARNT being master dimerization partner. The ARNT‐HIF‐1α complex is an important transcriptional regulator of the hypoxic response of the tumor cells. Previous studies have reported two transcript variants of the gene produced by alternative splicing in mouse. One transcript variant contains all 22 exons while the other variant lacks exon‐E5. In our study, using combinatorial approach comprising bioinformatics tools and molecular biology techniques involving RT‐PCR, semi‐nested PCR, sequencing and qPCR, we have identified three novel transcript variants of Arnt gene in mouse. All three new transcripts arise as a result of alternative splicing of newly identified exons with exon‐E2, replacing reported exon‐E1. These transcripts encode for three protein isofoms having different N‐termini. The expression of these transcripts was found to be different in different tissues of adult mice. In silico analysis of the upstream region of the new exons revealed three distinct promoter regions designated as PA, PB and PC present upstream of newly identified exons. These promoters possess potential signature sequences for common as well as different transcription factors suggesting complex regulation of Arnt gene. In silico post translational studies of the conceptually translated amino acid sequences of these transcripts show similarity in some of the properties while differ in others. The diversity at N‐termini of protein isoforms suggests the possibility of forming different complexes in different tissues and may also be important for unique interactions with partner molecules. © 2015 IUBMB Life, 68(2):122–135, 2016
Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity
Authors: Paolini Alessandro , Guarch Constança Porredon , Ramos‐López David , de Lapuente Joaquín , Lascialfari Alessandro , Guari Yannick , Larionova Joulia , Long Jerome , Nano Rosanna
Published: December 2015

Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron‐oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose‐coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells’ uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose‐coated iron‐oxide nanoparticles for future MFH therapeutic treatments. Copyright © 2015 John Wiley & Sons, Ltd.
History and trends of bioactive glass‐ceramics
Authors: Montazerian Maziar , Dutra Zanotto Edgar
Published: December 2015

The interest around bioactive glass‐ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter‐crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1231–1249, 2016.
Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone
Authors: Wang Xiaodu , Xu Haoran , Huang Yehong , Gu Sumin , Jiang Jean X
Published: December 2015

Proteoglycans (PGs) are one type of noncollagenous proteins in the extracellular matrix of bone that primarily contain a core protein and glycosaminoglycans (GAGs). GAGs are highly polar and negatively charged, thus have a strong tendency to attract water molecules into the matrix. We hypothesized in this study that PGs in bone play a pivotal role in sustaining the toughness of the tissue only when water is present. To test the hypothesis, we used a novel nanoscratch test to measure the in situ toughness of human cadaveric bone treated with and without peptide-N-glycosidase F (PNGase F), an enzyme that specifically removes the N-linked oligosaccharides of GAGs from core proteins. Cortical bone specimens were prepared from the posterior aspect of mid-diaphyseal femurs of six (n = 6) male human donors between 51.5 ± 5.17 years old. Biochemical and histochemical assays were used to verify whether N-linked oligosaccharides were removed from bone matrix by PNGase F. By testing wet and dehydrated bone specimens, the coupling effect between water and PGs on the in situ toughness of bone was investigated. The two-way ANOVA analyses showed that removal of GAGs had significant effects on the in situ toughness of wet bone samples. In contrast, the removal of GAGs did not show significant effects on the toughness of dry bone. The results of this study, for the first time, suggest that GAGs play a pivotal role in the in situ toughness of bone only when water is present, and vice versa, water functions as a plasticizer in bone only when GAGs are present. © 2015 American Society for Bone and Mineral Research.
Downregulation of Microrna‐148a in Cancer‐Associated Fibroblasts from Oral Cancer Promotes Cancer Cell Migration and Invasion by Targeting Wnt10b
Authors: Min Anjie , Zhu Chao , Peng Shuping , Shuai Cijun , Sun Lu , Han Ying , Qian Yunmei , Gao Shan , Su Tong
Published: December 2015

It is well established that crosstalk between cancer‐associated fibroblasts (CAFs) and cancer cells plays a critical role in the occurrence and development of oral squamous cell carcinoma (OSCC). The molecular mechanisms underlying such interaction, however, remain far from clear. Accumulating data have indicated that microRNAs involved in tumor microenvironment, particularly in CAFs, contribute to the activation of fibroblasts and metastasis of cancer cells. Here, we showed that miR‐148a was downregulated in CAFs compared with normal fibroblasts isolated from clinical OSCC tissue. Investigation of miR‐148a function in fibroblasts demonstrated that overexpression of miR‐148a in CAFs significantly impaired the migration and invasion of oral carcinoma cells (SCC‐25) by directly targeting WNT10B. Taken together, these data suggested that miR‐148a might be a novel candidate target for the treatment of OSCC.
The Flame‐Retardant Tris(1,3‐dichloro‐2‐propyl) Phosphate Represses Androgen Signaling in Human Prostate Cancer Cell Lines
Authors: Reers Alexandra R. , Eng Margaret L. , Williams Tony D. , Elliott John E. , Cox Michael E. , Beischlag Timothy V.
Published: December 2015

The effects of six organophosphate flame retardants (OPFRs) tris(2‐butoxyethyl) phosphate, tris(2‐chloroethyl) phosphate, tris(1‐chloro‐2‐propyl) phosphate, tris(methylphenyl) phosphate, tris(1,3‐dichloro‐2‐propyl) phosphate (TDCIPP), and triethyl phosphate on the activities of androgen receptor (AR), estrogen receptor (ER), and aryl hydrocarbon receptor (AhR) were assessed in human prostate and endometrial cancer cells. OPFRs had no effect on ER or AhR target gene activation in ECC‐1 cells. The effect of TDCIPP on mRNA and protein accumulation of AR target genes was examined further. AR‐inducible gene and protein expression were significantly altered by TDCIPP exposure and repressed PSA levels in conditioned media of prostate cancer cells. We demonstrated that TDCIPP has no affinity for the AR ligand binding domain (AR‐LBD) and exerts its antiandrogenic effects in a noncompetitive fashion. Thus, the clinical relevance of TDCIPP exposure on prostate cancer detection and progression to a therapeutically refractile state ought to be investigated further.
Development of 6‐[18F]fluoro‐carbohydrate‐based prosthetic groups and their conjugation to peptides via click chemistry
Authors: Collet Charlotte , Maskali Fatiha , Clément Alexandra , Chrétien Françoise , Poussier Sylvain , Karcher Gilles , Marie Pierre‐Yves , Chapleur Yves , Lamandé‐Langle Sandrine
Published: December 2015

This work describes the development of new 6‐[18F]fluoro‐carbohydrate‐based prosthetic groups equipped with an azido arm that are able to participate in copper(I)‐catalyzed cycloadditions for 18F labeling of biomolecules under mild conditions. The radiolabeling in high radiochemical yields (up to 68 ± 6%) of these different prosthetic groups is presented. The flexibility of the azido arm introduced on the carbohydrate moieties allows efficient click reactions with different alkyne functionalized peptides such as gluthation or Arg‐Gly‐Asp derivatives in order to prepare glycopeptides. The radiosyntheses of 18F‐labeled glycopeptides proceed in high radiochemical yields (up to 76%) in an automated process with excellent radiochemical purity. The addition of a sugar moiety on peptides should enhance the bioavailability, pharmacokinetic, and in vivo clearance properties of these glycopeptides, compared with the unlabeled native peptide, and these properties are highly favorable for positron emission tomography imaging. A high uptake of 18F‐β‐gluco‐c(RGDfC) is shown by positron emission tomography imaging in a subcutaneous abscess model in the rat, revealing the potential of this tracer to monitor integrin expression as a part of inflammation and/or angiogenesis processes.
Assessment of liver fibrosis using pharmacokinetic parameters of dynamic contrast‐enhanced magnetic resonance imaging
Authors: Li Zhiming , Sun Jihong , Chen Lumin , Huang Ning , Hu Peng , Hu Xi , Han Guocan , Zhou Yurong , Bai Weixian , Niu Tianye , Yang Xiaoming
Published: December 2015

Purpose

To evaluate the pharmacokinetic parameters of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in diagnosing and staging liver fibrosis in rabbits.

Materials and Methods

DCE‐MRI with gadodiamide (Gd‐DTPA‐BMA) was performed on a 3.0 Tesla, 60 cm bore MR scanner for rabbits with CCl4‐induced liver fibrosis, and an untreated control group. Fibrosis was staged according to the METAVIR system: control (F0; n = 13), nonadvanced fibrosis (F1–2; n = 15), and advanced fibrosis (F3–4; n = 12). The DCE‐MRI parameters Ktrans, kep, Ve, and vp were measured with a dual‐input extended Tofts model. Receiver operating characteristic analyses were performed to assess the diagnostic performance of Ktrans, Ve, and vp in staging liver fibrosis.

Results

Both Ktrans and Ve decreased with increasing fibrosis stage. Ktrans of the control group was significantly different from that of the overall fibrosis group, nonadvanced group, and advanced group (P < 0.001 for all). Significant differences were found between Ve of the control group and that of the overall fibrosis and advanced groups (P = 0.019 and P = 0.009, respectively). For Ktrans, the areas under the receiver operating characteristic curve (AUROCs) for discriminating the control group from the overall fibrosis and advanced fibrosis groups were 0.909 (95% confidence interval [CI], 0.809–1.000), and 0.936 (95% CI,0.847–1.000), respectively. For discriminating between the control and nonadvanced fibrosis groups, the AUROC of Ktrans was 0.887 (95% CI, 0.762–1.000). The AUROCs of Ktrans were higher than those of Ve and vp for discriminating between the control and overall fibrosis groups, the control and nonadvanced fibrosis groups, and the control and advanced fibrosis groups. Pharmacokinetic parameters were negatively correlated with fibrosis stage (Ktrans, rho = ‐0.668, P < 0.001; Ve, rho = ‐0.438, P = 0.005; vp, rho = ‐0.360, P = 0.023).

Conclusion

Among pharmacokinetic parameters of DCE‐MRI in our study, Ktrans was an excellent predictor for differentiating fibrotic livers from normal livers, and differentiating normal livers from nonadvanced or advanced fibrosis livers. J. Magn. Reson. Imaging 2016;44:98–104.
Evaluation of upper airway collapsibility using real‐time MRI
Authors: Wu Ziyue , Chen Weiyi , Khoo Michael C.K. , Davidson Ward Sally L. , Nayak Krishna S.
Published: December 2015

Purpose

To develop and demonstrate a real‐time MRI method for assessing upper airway collapsibility in sleep apnea.

Materials and Methods

Data were acquired on a clinical 3 Tesla scanner using a radial CAIPIRIHNA sequence with modified golden angle view ordering and reconstructed using parallel imaging and compressed sensing with temporal finite difference sparsity constraint. Segmented airway areas together with synchronized facemask pressure were used to calculate airway compliance and projected closing pressure, Pclose, at four axial locations along the upper airway. This technique was demonstrated in five adolescent obstructive sleep apnea (OSA) patients, three adult OSA patients and four healthy volunteers. Heart rate, oxygen saturation, facemask pressure, and abdominal/chest movements were monitored in real‐time during the experiments to determine sleep/wakefulness.

Results

Student's t‐tests showed that both compliance and Pclose were significantly different between healthy controls and OSA patients (P < 0.001). The results also suggested that a narrower airway site does not always correspond to higher collapsibility.

Conclusion

With the proposed methods, both compliance and Pclose can be calculated and used to quantify airway collapsibility in OSA with an awake scan of 30 min total scan room time. J. Magn. Reson. Imaging 2016;44:158–167.
Mesenchymal stem cells attenuate peripheral neuronal degeneration in spinocerebellar ataxia type 1 knockin mice
Authors: Mieda Tokue , Suto Nana , Iizuka Akira , Matsuura Serina , Iizuka Haku , Takagishi Kenji , Nakamura Kazuhiro , Hirai Hirokazu
Published: December 2015

Spinocerebellar ataxia type 1 (SCA1) is a devastating neurodegenerative disorder in which an abnormally expanded polyglutamine tract is inserted into causative ataxin‐1 proteins. We have previously shown that SCA1 knockin (SCA1‐KI) mice over 6 months of age exhibit a degeneration of motor neuron axons and their encasing myelin sheaths, as reported in SCA1 patients. We examined whether axon degeneration precedes myelin degeneration or vice versa in SCA1‐KI mice and then attempted to mitigate motor neuron degeneration by intrathecally administering mesenchymal stem cells (MSCs). Temporal examination of the diameters of motor neuron axons and their myelin sheaths revealed a decrease in diameter of the axon but not of the myelin sheaths in SCA1‐KI mice as early as 1 month of age, which suggests secondary degeneration of the myelin sheaths. We injected MSCs into the intrathecal space of SCA1‐KI mice at 1 month of age, which resulted in a significant suppression of degeneration of both motor neuron axons and myelin sheaths, even 6 months after the MSC injection. Thus, MSCs effectively suppressed peripheral nervous system degeneration in SCA1‐KI mice. It has not yet been clarified how clinically administered MSCs exhibit significant therapeutic effects in patients with SCA1. The morphological evidence presented in this current mouse study might explain the mechanisms that underlie the therapeutic effects of MSCs that are observed in patients with SCA1. © 2015 Wiley Periodicals, Inc.
Collision‐independent detection of molecular two‐photon excitation by time‐resolved parametric four‐wave mixing
Authors: Stauffer Hans U. , Wrzesinski Paul J. , Roy Sukesh , Kulatilaka Waruna D. , Gord James R.
Published: December 2015

We report collision‐independent detection of gas‐phase nitric oxide (NO) via a two‐pulse, femtosecond (fs) time‐resolved parametric four‐wave‐mixing (PFWM) optical‐probe scheme. This approach exploits the broadband two‐photon excitation of rovibrational manifolds associated with resonant electronic molecular transitions, allowing species‐specific detection. The observed time‐domain fs‐PFWM spectral signature associated with this broadband electronic two‐photon excitation process is shown to exhibit negligible dependence on colliding‐partner concentrations at short (<10 ps) time delays, even in the presence of species that strongly quench excited‐state fluorescence. Furthermore, by employing a hybrid fs/ps PFWM scheme, the broadband two‐photon absorption spectrum of the molecular species of interest is demonstrated to be resolved in the wavenumber domain without need to scan the probe‐pulse delay. Copyright © 2015 John Wiley & Sons, Ltd.
Ki67—An unsuitable marker of gastric cancer prognosis unmasks intratumoral heterogeneity
Authors: Böger Christine , Behrens Hans‐Michael , Röcken Christoph
Published: December 2015

Background and Objectives

Due to contradictious findings of previous studies regarding Ki67's value in gastric cancer (GC), we reevaluated the expression of Ki67 in whole tissue sections (WTS) and tissue microarrays (TMAs) of GC testing the following hypotheses: does Ki67 show intratumoral heterogeneity; are TMAs representative in the determination of the Ki67 proliferation index (PI); is the Ki67 PI subject to an intralaboratory variability; and is the Ki67 PI related to clinico‐pathological patient characteristics and/or prognostically relevant in GC.

Methods

Corresponding WTS and TMAs samples from 315 GCs were stained immunohistochemically. The Ki67 PI evaluated on WTS was correlated with the Ki67 PI evaluated on TMAs, sample age, clinico‐pathological characteristics, and patient survival.

Results

The overall amount of Ki67‐positive tumor cells did not depend on sample age. Three distinct, partly heterogeneous Ki67 expression patterns were observed. The mean Ki67 PI evaluated on TMAs differed on average minus 16.9% from the Ki67 PI evaluated on WTS. Ki67 in WTS correlated significantly with the Laurén phenotype and tumor grade, but not with patient survival.

Conclusion

TMAs carry the risk of a systematic underestimation of the Ki67 PI. Ki67 has no prognostic value in GC but might be a potential indicator of intratumoral heterogeneity. J. Surg. Oncol. 2016;113:46–54. © 2015 The Authors. Journal of Surgical Oncology published by Wiley Periodicals, Inc.
Predictors of high‐risk and low‐risk oral HPV infection in the United States
Authors: Orosco Ryan K. , Kedarisetty Suraj , Hecht Avram S. , Chang David C. , Coffey Charles S. , Weissbrod Philip A.
Published: December 2015

Objectives/Hypothesis

Determine predictors of high‐risk and low‐risk oral HPV infection in the United States.

Study Design

Retrospective analyses of National Health and Nutrition Examination Survey cross‐sectional data of U.S. population from 2009 to 2012.

Methods

Database queried for subjects aged 18 to 69 with oral rinse human papillomavirus (HPV) DNA data. Logistic regression identified factors associated with high‐risk and low‐risk infection. Covariates included age, gender, ethnicity, income‐to‐poverty (IP) ratio, sexual orientation, human immunodeficiency virus infection, other sexually transmitted infections, lifetime sexual partners, and lifetime oral sex partners.

Results

In total, 9,256 subjects were identified with mean age of 42.1 years. Oral HPV infection was present in 8.1% (N = 747); 55.7% were high‐risk and 55.3% were low‐risk types, including 11% with both. Oral infection had a negative association with female gender (odds ratio [OR] 0.3, P < 0.001), IP ratio ≥ 3 (OR 0.7, P = 0.02), and one lifetime oral sex partner (OR 0.7, P = 0.03). Increasing oral sex behavior (6–21+ lifetime partners) was positively associated with oral HPV (OR 1.4–3.0, P = 0.03). Low‐risk infection had negative associations with female gender (OR 0.4, P < 0.001) and non‐Hispanic white ethnicity (OR 0.6, P = 0.02), IP ratio ≥ 3 (OR 0.6, P = 0.01), and positive association with > 20 sexual partners (all sex OR 1.7, P = 0.04; oral sex OR 1.9, P = 0.02). Predictors of high‐risk HPV infection included male gender and increasing oral sex partners.

Conclusion

Increasing oral sex partners is positively associated with oral HPV infection; female sex and higher socioeconomic class are negatively associated. The risk‐factor profiles for high‐risk and low‐risk HPV types are distinct, with similar trends related to sexual behaviors.

Level of Evidence

4. Laryngoscope, 126:1365–1372, 2016
Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high‐risk liver transplantation recipients: A propensity score analysis
Authors: Fortún Jesús , Muriel Alfonso , Martín‐Dávila Pilar , Montejo Miguel , Len Oscar , Torre‐Cisneros Julian , Carratalá Jordi , Muñoz Patricia , Fariñas Maria Carmen , Moreno Asunción , Fresco Gema , Goikoetxea Josune , Gavaldá Joan , Pozo Juan Carlos , Bodro Marta , Vena Antonio , Casafont Fernando , Cervera Carlos , Silva José Tiago , Aguado José M. ,   and for the Grupo de Estudio de Infección en Pacientes Trasplantados—Grupo de Estudio de Micología Médica (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica), and Red Española de Investigación en Patología Infecciosa
Published: December 2015

Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high‐risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR‐LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005‐2012), we analyzed 195 HR‐LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001‐0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR‐LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR‐LTRs, although bilirubin levels may be increased.
Designing Visible Light‐Cured Thiol‐Acrylate Hydrogels for Studying the HIPPO Pathway Activation in Hepatocellular Carcinoma Cells
Authors: Lin Tsai‐Yu , Bragg John C. , Lin Chien‐Chi
Published: December 2015

Various polymerization mechanisms have been developed to prepare peptide‐immobilized poly(ethylene glycol) (PEG) hydrogels, a class of biomaterials suitable for studying cell biology in vitro. Here, a visible light mediated thiol‐acrylate photopolymerization scheme is reported to synthesize dually degradable PEG‐peptide hydrogels with controllable crosslinking and degradability. The influence of immobilized monothiol pendant peptide is systematically evaluated on the crosslinking of these hydrogels. Further, methods are proposed to modulate hydrogel crosslinking, including adjusting concentration of comonomer or altering the design of multifunctional peptide crosslinker. Due to the formation of thioether ester bonds, these hydrogels are hydrolytically degradable. If the dithiol peptide linkers used are susceptible to protease cleavage, these thiol‐acrylate hydrogels can be designed to undergo partial proteolysis. The differences between linear and multiarm PEG‐acrylate (i.e., PEGDA vs PEG4A) are also evaluated. Finally, the use of the mixed‐mode thiol‐acrylate PEG4A‐peptide hydrogels is explored for in situ encapsulation of hepatocellular carcinoma cells (Huh7). The effects of matrix stiffness and integrin binding motif (e.g., RGDS) on Huh7 cell growth and HIPPO pathway activation are studied using PEG4A‐peptide hydrogels. This visible light poly­merized thiol‐acrylate hydrogel system represents an alternative to existing light‐cured hydrogel platforms and shall be useful in many biomedical applications.
EFFECTS OF A UNIVERSAL POSITIVE CLASSROOM BEHAVIOR PROGRAM ON STUDENT LEARNING
Authors: Diperna James Clyde , Lei Puiwa , Bellinger Jillian , Cheng Weiyi
Published: December 2015

The purpose of this study was to examine the impact of a universal program to promote positive classroom behavior on students’ approaches to learning and early academic skills. Second grade classrooms (N = 39) were randomly assigned to treatment and business‐as‐usual control conditions. Teachers in intervention classrooms implemented the Social Skills Improvement System Classwide Intervention Program (SSIS‐CIP) over a 12‐week period. Participating students’ (N = 494) engagement, motivation, and academic skills were assessed before and after treatment implementation. Results indicated that students with lower levels of engagement and motivation at pretest experienced significant improvement in these areas after exposure to the SSIS‐CIP. Although no significant differences were observed in reading, students receiving supplemental instructional services demonstrated greater gains in mathematics than did their peers in the control condition.
EDUCATORS’ REPORTS ON INCIDENCE OF HARASSMENT AND ADVOCACY TOWARD LGBTQ STUDENTS
Authors: Dragowski Eliza A , McCabe Paul C , Rubinson Florence
Published: December 2015

This study is based on a national survey investigation of 968 educators, who reported the incidence of LGBTQ harassment in schools, and their advocacy efforts on behalf of this population. LGBTQ‐related knowledge, attitudes, norms, and perceived ability to advocate were also assessed. Ninety percent of educators reported observing LGBTQ harassment and 30% consistently intervened. Overall, educators reported positive attitudes towards LGBTQ people, felt professionally supported, and ready for LGBTQ advocacy. Educators reported inadequate knowledge of LGBTQ identity development and desire for professional development. School counselors were more informed about LGBTQ issues and more aware of LGBTQ harassment than school psychologists or teachers.
Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization in ionic liquid
Authors: Zhou Heng , Liu Chonggao , Gao Chengqiang , Qu Yaqing , Shi Keyu , Zhang Wangqing
Published: December 2015

Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization has been demonstrated to be a valid method to prepare block copolymer nano‐objects. However, volatile solvents are generally involved in this preparation. Herein, the in situ synthesis of block copolymer nano‐objects of poly(ethylene glycol)‐block‐polystyrene (PEG‐b‐PS) in the ionic liquid of 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([BMIN][PF6]) through the macro‐RAFT agent mediated dispersion polymerization is investigated. It is found that the dispersion RAFT polymerization of styrene in the ionic liquid of [BMIN][PF6] runs faster than that in the alcoholic solvent, and the dispersion RAFT polymerization in the ionic liquid affords good control over the molecular weight and the molecular weight distribution of the PEG‐b‐PS diblock copolymer. The morphology of the in situ synthesized PEG‐b‐PS diblock copolymer nano‐objects, e.g., nanospheres and vesicles, in the ionic liquid is dependent on the polymerization degree of the solvophobic block and the concentration of the fed monomer, which is somewhat similar to those in alcoholic solvent. It is anticipated that the dispersion RAFT polymerization in ionic liquid broads a new way to prepare block copolymer nano‐objects. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1517–1525
Hyperbranched polybenzoxazoles incorporated polybenzoxazoles for high‐performance and low‐Kmaterials
Authors: Wang Yan , Yu Junrong , Zhu Jing , Hu Zuming
Published: December 2015

This paper reports an effective approach for the fabrication of low‐kpolybenzoxazole (PBO) by covalent incorporation of hyperbranched PBO (HBPBO). Solubleo‐aminophenol‐terminated HBPBO was first synthesized by a one‐pot polycondensation, then covalently bonded to poly(hydroxyamide) ended with carbonyl chloride groups, PBO was finally obtained by thermal conversion of the precursor polymers. It was demonstrated that the thermal stability of PBO was not influenced by the incorporation of HBPBO due to their similar chemical compositions, while the glass transition temperature, elastic modulus and hardness were improved because of the linking effects of HBPBO to linear PBO chains. The dielectric constant of PBO was significantly reduced due to the disturbed chain packing of PBO by the globular HBPBO, and the intrinsic cavities in HBPBO, which increased free volume in the materials. Moreover, the material also exhibited reduced coefficient of thermal expansion as compared to neat PBO and low water absorption. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2016,54, 1623–1632
Addicted to Government? The Impact of Housing Assistance on Program Participation of Welfare Recipients
Authors: Haley Barbara A. , Dajani Aref N.
Published: December 2015

This research addresses the question of whether housing assistance provided a perverse incentive for welfare recipients to remain on the rolls following the enactment of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996. Merging the 1996 Survey of Income and Program Participation (SIPP) with HUD's administrative records provides a unique opportunity to test whether recipients of housing assistance were more likely to stay on the welfare program four years after the enactment of PRWORA. This dataset contains a nationally representative sample of welfare recipients. Quarterly data, including sources of income, were obtained from these families of welfare recipients for four years. Results indicate that in an era of plunging welfare rolls, receipt of housing assistance did not account for those who remained on Temporary Assistance to Needy Families (TANF). These data show that housing assistance was not a perverse incentive to remain on welfare in the aftermath of the welfare reform of 1996. Instead, those who failed to exit the rolls four years after TANF was enacted had high obligations to children, lacked prior participation in the labor force, and lacked access to an automobile.
Implementing the ACA: The Influence of Nurse Practitioner Regulatory Policies on Workforce, Access to Care, and Primary Care Health Outcomes
Authors: Sonenberg Andréa , Knepper Hillary , Pulcini Joyce
Published: December 2015

The Patient Protection and Affordable Care Act P.L. 111–148 (ACA) was projected to expand health insurance to about 32 million people by 2014. This influx presents significant pressures for primary health care providers (PCP) at a time when there is already a PCP shortage. The associations among prevention, equity, healthy environments, nurse practitioner (NP) regulatory policies, and access to primary care are well documented in the literature. This article presents relationships among NP scope of practice regulations in the 50 states and the District of Columbia and their potential impact on population health outcomes. Utilizing correlation and multiple regression analyses, this study identifies modest but significant associations. In accordance with Institute of Medicine (2011) recommendations, the authors suggest successful implementation of the ACA requires modernization and standardization of existing NP practice regulatory policies in order to build primary care capacity, increase access, and improve population health.
To What Extent Are Greek Children Exposed to the Risk of a Lifelong, Intergenerationally Transmitted Poverty?
Authors: Mentis Alexios‐Fotios A.
Published: December 2015

Today Greece is confronted with an unprecedented humanitarian crisis. Children of the recession live under conditions of poverty and deprivation. Within four years from the onset of crisis, child poverty rates almost doubled. Two out of five children are living below the poverty line (40.5 percent), whereas 23.2 percent are currently living in extreme material deprivation. Their families have parents who are jobless or “in‐work poor.” The Greek Orthodox Church delivers meals to over 500,000 people every day, as do municipal authorities either directly or by sustaining families’ nutrition through social food banks. Child poverty existed in unacceptably high rates even when other economic indicators, such as unemployment or pace of economic growth, were favorable. Thus, an already weak and inefficient welfare state could not buffer children when the financial crisis erupted. Unemployment has slightly (1 percent) receded for the first time in 2014, but still approximately 27 percent of the active population is jobless. Moreover, significant income losses make “in‐work poor” people unable to earn enough money for their living, especially when the family has one or two children. Briefly, 1,225,857 people are still being cast aside from the labor market, while 2,724,539 (35.7 percent) live under the “poverty line.” The risk that children already in family poverty will be unable to obviate the trap is real. To the emerging question “Could the state intervene through appropriate transmissions and avert the lifelong perspective?” we argue that, despite depletion of funds for social spending, public transmissions in general may avert this perspective if better targeted, and that policy responses in other countries have managed to protect children far better in comparison to Greece.
Vulnerability Dimensions and Access to Affordable Housing: The Case of the Waste Picker Community in Amritsar City, India
Authors: Sandhu Kiran
Published: December 2015

Concentration of urban poverty within the milieu of rampant urbanization in the neoliberalist era and its manifestation in the forms of informalities in housing and infrastructure access and occupation has become more of a rule rather than an exception in cities of the developing world. The Indian cities are no exception to this trend. However, the filtration of the benefits aiming to remove urban disparities by providing access to housing and infrastructure to the most vulnerable poor communities has remained elusive. Resultantly, the poorest sections continue to remain “invisible” on the radar of the city housing reforms and provision agenda. Left to fend for themselves, they respond by creating informal and precarious housing solutions on their own, sadly unrecognized and sidelined by state interventions. The research article investigates the vulnerabilities afflicting the waste picker community through detangling physical, social, economic, and politico‐legal vulnerability dimensions and their access to affordable housing in the formal sector. The article argues that affordable housing remains more of an allegory than a veracity for the most vulnerable communities such as the waste pickers and emphasizes recognition of the multidimensional vulnerabilities and protecting their right to live with dignity, free of contestations and threat of evictions.
Editor's Letter
Authors: Skidmore Max J.
Published: December 2015

Editor‐in‐Chief Max J. Skidmore discusses Volume 7, Issue 4, of Poverty and Public Policy, the fourth and final quarterly issue of 2015.
One‐year safety and efficacy of tobramycin powder for inhalation in patients with cystic fibrosis
Authors: Konstan Michael W. , Flume Patrick A. , Galeva Ivanka , Wan Robert , Debonnett Laurie M. , Maykut Robert J. , Angyalosi Gerhild
Published: December 2015

This is an integrated analysis of data from patients with cystic fibrosis (CF) aged 6–21 years who were treated with up to seven cycles of tobramycin powder for inhalation (TIPTM) over a period of at least 1 year. Safety and key efficacy endpoints were analyzed. Results: The improvement in lung function and decrease in sputum P. aeruginosa (Pa) density from baseline were sustained over the 1‐year treatment period. The number of adverse events (AEs) was low and did not increase with additional cycles of TIP treatment. Some increase in tobramycin minimum inhibitory concentration (MIC) was observed, but there was no significant increase in emergence of resistant strains based on the parenteral breakpoint for tobramycin. Conclusion: Efficacy of TIP was maintained for up to seven cycles. Long‐term treatment with TIP was generally safe and well tolerated with no increase in AEs. Pediatr Pulmonol. 2016;51:372–378. © 2015 Wiley Periodicals, Inc.
Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma
Authors: Kibel Adam S. , Ahn Jiyoung , Isikbay Masis , Klim Aleksandra , Wu William S. , Hayes Richard B. , Isaacs William B. , Daw E. Warwick
Published: December 2015

BACKGROUND

Because a significant number of patients with prostate cancer (PCa) are diagnosed with disease unlikely to cause harm, genetic markers associated with clinically aggressive PCa have potential clinical utility. Since cell cycle checkpoint dysregulation is crucial for the development and progression of cancer, we tested the hypothesis that common germ‐line variants within cell cycle genes were associated with aggressive PCa.

METHODS

Via a two‐stage design, 364 common sequence variants in 88 genes were tested. The initial stage consisted of 258 aggressive PCa patients and 442 controls, and the second stage added 384 aggressive PCa Patients and 463 controls. European‐American and African‐American samples were analyzed separately. In the first stage, SNPs were typed by Illumina Goldengate assay while in the second stage SNPs were typed by Pyrosequencing assays. Genotype frequencies between cases and controls were compared using logistical regression analysis with additive, dominant and recessive models.

RESULTS

Eleven variants within 10 genes (CCNC, CCND3, CCNG1, CCNT2, CDK6, MDM2, SKP2, WEE1, YWHAB, YWHAH) in the European‐American population and nine variants in 7 genes (CCNG1, CDK2, CDK5, MDM2, RB1, SMAD3, TERF2) in the African‐American population were found to be associated with aggressive PCa using at least one model. Of particular interest, CCNC (rs3380812) was associated with risk in European‐American cohorts from both institutions. CDK2 (rs1045435) and CDK5 (rs2069459) were associated with risk in the African‐American cohorts from both institutions. Lastly, variants within MDM2 and CCNG1 were protective for aggressive PCa in both ethnic groups.

CONCLUSIONS

This study confirms that polymorphisms within cell cycle genes are associated with clinically aggressive PCa. Validation of these markers in additional populations is necessary, but these markers may help identify patients at risk for potentially lethal carcinoma. Prostate 76:479–490, 2016. © 2015 Wiley Periodicals, Inc.
NF‐κB and androgen receptor variant expression correlate with human BPH progression
Authors: Austin David C. , Strand Douglas W. , Love Harold L. , Franco Omar E. , Jang Alex , Grabowska Magdalena M. , Miller Nicole L. , Hameed Omar , Clark Peter E. , Fowke Jay H. , Matusik Robert J. , Jin Ren J. , Hayward Simon W.
Published: December 2015

BACKGROUND

Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α‐reductase inhibitor (5ARI) therapy. Activation of the nuclear factor‐kappa B (NF‐κB) pathway is linked to both inflammation and ligand‐independent prostate cancer progression.

METHODS

NF‐κB activation and androgen receptor variant (AR‐V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF‐κB activity. The effects on AR full length (AR‐FL) and androgen‐independent AR‐V expression as well as cellular growth and differentiation were assessed.

RESULTS

Canonical NF‐κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non‐insulin dependent diabetes mellitus. Elevated expression of AR‐variant 7 (AR‐V7), but not other AR variants, was found in advanced BPH samples. Expression of AR‐V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF‐κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR‐FL and AR‐V7, with concomitant ligand‐independent activation of AR reporters. Activation of NF‐κB and over expression of AR‐V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment.

CONCLUSION

Activation of NF‐κB and AR‐V7 in the prostate is associated with increased disease severity. AR‐V7 expression is inducible in human prostate cells by forced activation of NF‐κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy.Prostate 76:491–511, 2016. © 2015 Wiley Periodicals, Inc.
Control Charts for Process Dispersion Parameter under Contaminated Normal Environments
Authors: Ali Amjid , Mahmood Tahir , Nazir Hafiz Zafar , Sana Iram , Akhtar Noureen , Qamar Sadia , Iqbal Muhammad
Published: December 2015

Control charts are important statistical tool used to monitor fluctuations in the process location and dispersion parameters. The issues relating to the appropriate choice of control charts for the effective detection of process variability are addressed, and different control chart structures, such as Shewhart‐type, exponentially weighted moving average and cumulative sum are explored under ideal assumption of normality and contaminated normal environments, and hence, those control charts structures are identified which are more capable to detect aberrant changes in the process dispersion. Copyright © 2015 John Wiley & Sons, Ltd.
On Modified Successive Sampling Based Control Charting Schemes
Authors: Yaqub Mazhar , Abbas Nasir , Riaz Muhammad , Shabbir Javid
Published: December 2015

The presence of variation cannot be avoided in different kinds of manufacturing and non‐manufacturing processes. A better understanding of the causes of variability in any process is necessary to improve the process. Control chart is a very frequently used tool for checking whether the process parameters are stable or not. The current study devises a sampling technique, named as modified successive sampling scheme, that is not only cost‐effective but also efficient as compared with the simple random sampling scheme. A number of Shewhart‐type control charts are proposed based on the said sampling scheme, and average run length is used as a performance indicator. Based on the average run length values, all the proposed charts are compared with existing Shewhart control chart for both positive and negative shifts in the process. Finally, the new proposals are applied to a real dataset where the variable of interest is an inner diameter of automobile engine piston rings made of steel. Copyright © 2015 John Wiley & Sons, Ltd.