bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclodextrin complexes: Perspective from drug delivery and formulation
Authors: Jacob Shery , Nair Anroop B.
Published: September 2018

Cyclodextrins (CDs) have been widely investigated as a unique pharmaceutical excipient for past few decades and is still explored for new applications. They are highly versatile oligosaccharides which possess multifunctional characteristics, and are mainly used to improve the physicochemical stability, solubility, dissolution rate, and bioavailability of drugs. Stability constant, factors affecting complexation, techniques to enhance complexation efficiency, the preparation methods for molecular inclusion complexes and release of guest molecules are discussed in brief. In addition, different CD derivatives and their pharmacokinetics are elaborated. Further, the significance of CD complex in aqueous solubility, dissolution and bioavailability, stability, and taste masking is explained. The recent advancement of CDs in developing various drug delivery systems is enlightened. Indeed, the potential of CDs by means of inclusion complex formation have widen the applicability of these materials in various drug delivery systems including ocular, osmotic, mucoadhesive, transdermal, nasal, and targeted delivery systems. Feasibility studies have been performed on the benefit of these cyclic oligomers as nanocarriers, a strategy that can modify the drugs with improved physicochemical properties. Studies also demonstrated the feasibility of CDs to self‐assemble in the form of stable nanoaggregates, which may extend the scope of CDs in drug delivery to the continually expanding list of new drug entities.
Rigor, reproducibility, and novel methodological approaches to eating disorders research
Authors: Hildebrandt Tom , Crosby Ross D.
Published: September 2018

The explosion of new methods in science has put additional pressure on authors, readers, and peer reviewers to evaluate the rigor and reproducibility of these new approaches. This issue brings together a collection of articles aimed to stimulate our thinking about how to evaluate the quality of these new methodologies, in the form of several expert reviews on domains ranging from large scale genetics to clinical interventions. These expert reviews are followed by a collection of papers intended to illustrate new or underrepresented methods in our field and include novel approaches to clinical trials to the quantification of text data collected from public repositories online. The issue concludes with a number of original data papers applying network analysis to study comorbidity and symptom status in eating disorder and related populations and a couple of novel neuroimaging papers demonstrating the use of new and promising methods for studying heterogeneity and the use of psychophysiology to answer questions about emotion in eating disorder populations.
Improved numerical analysis for ultimate behavior of elastomeric seismic isolation bearings
Authors: Ishii Ken , Kikuchi Masaru
Published: September 2018

Elastomeric isolation bearings consist of multiple rubber layers with their top and bottom surfaces bonded to steel plates to restrict compressive deformation. Deformation constraints result in a variation of elastic modulus over the cross section of the rubber layers. In this paper, we describe a normalized compression modulus distribution on a circular rubber pad. The compressive and bending moduli of the rubber pad can be reproduced by applying the distribution to a series of axial springs. We also present a mechanical model for predicting the behavior of elastomeric seismic isolation bearings subject to large shear deformation and high compressive load. The mechanical model consists of a series of multiple shear springs at midheight and a series of axial springs at the top and bottom interfaces of the bearing. Simulation analyses of bearing tests were conducted to validate the proposed model. The analyses demonstrated that a model for circular lead‐rubber bearings can successfully capture the influence of the axial load magnitude on the bearing shear behavior. The new model can simulate much more realistic behavior than prior models based on a uniform modulus assumption.
Management of adverse events associated with idelalisib treatment in chronic lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper
Authors: Cuneo Antonio , Barosi Giovanni , Danesi Romano , Fagiuoli Stefano , Ghia Paolo , Marzano Alfredo , Montillo Marco , Poletti Venerino , Viale Pierluigi , Zinzani Pier Luigi
Published: September 2018

The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib.
Mongolian Health Sector Strategic Master Plan (2006‐2015): A foundation for achieving universal health coverage
Authors: Erdenee Oyunchimeg , Narula Indermohan S. , Yamazaki Chiho , Kameo Satomi , Koyama Hiroshi
Published: September 2018

Nearly half of the countries in the world are in the process of reforming and strengthening their health care systems. More recently, even low‐income and middle‐income countries such as Mongolia have focused increasing attention on achieving universal health coverage (UHC). At this critical point, it is necessary to track recent progress and adjust health care strategies and planning. Therefore, this study analyzed changes in the health sector toward achieving UHC based on relevant literature, government documents, and framework analysis. We also investigated how basic principles of UHC were incorporated and reflected in Mongolia's Health Sector Strategic Master Plan. This study clarified the achievements of and challenges facing the health sector that remain or emerged during the plan's implementation over the last decade. Furthermore, all of the reviewed Master Plan strategies were underpinned by basic principles of UHC. However, strategies set out in the next Master Plan will require adjustments and innovative measures to respond to current challenges. This study may be used as a reference for other developing countries to track UHC achievements and serve as a guide to establishing a nation‐wide strategic plan.
Dual Stimuli‐Responsive Cross‐Linked AIE Supramolecular Polymer Constructed through Hierarchical Self‐Assembly
Authors: Zhang Chang‐Wei , Jiang Shu‐Ting , Yin Guang‐Qiang , Li Xiaopeng , Zhao Xiao‐Li , Yang Hai‐Bo
Published: September 2018

Herein, we report the successful construction of a new family of dual stimuli‐responsive AIE cross‐linked supramolecular polymer through the strategy of hierarchical self‐assembly. A novel dipyridyl donor building block G1 containing tetraphenylethylene (TPE) moiety was designed and synthesized. Notably, two nitrile units were attached onto G1, which were employed as the guest for the further host‐guest interaction with pillar[n]arene derivatives. The rhomboidal metallacycle G2 with four nitrile units was firstly constructed through coordination‐driven self‐assembly. Subsequently, the cross‐linked supramolecular polymers H2⊃G2 were then generated through host‐guest interactions. It should be noted that the obtained supramolecular polymer displayed interesting AIE properties due to the restriction of TPE intramolecular motions within the polymeric network. More importantly, by taking advantages of dynamic nature of both coordination bonds and host‐guest interactions, the resultant supramolecular polymer displayed dual stimuli‐responsive fluorescent transitions under different stimuli such as the competitive guest and halide anion.
Hyperspectral scanning laser optical tomography
Authors: Chen Lingling , Li Guiye , Tang Li , Zhang Meng , Liu Lina , Liu Ang , McGinty James , Ruan Shuangchen
Published: September 2018

In order to study physical relationships within tissue volumes or even organism‐level systems, the spatial distribution of multiple fluorescent markers needs to be resolved efficiently in three dimensions. Here, rather than acquiring discrete spectral images sequentially using multiple emission filters, a hyperspectral scanning laser optical tomography system is developed to obtain hyperspectral volumetric data sets with 2‐nm spectral resolution of optically transparent mesoscopic (millimeter‐centimeter) specimens. This is achieved by acquiring a series of point‐scanning hyperspectral extended depth of field images at different angles and subsequently tomographically reconstructing the 3D intensity distribution for each wavelength. This technique is demonstrated to provide robust measurements via the comparison of spectral and intensity profiles of fluorescent bead phantoms. Due to its enhanced spectral resolving ability, this technique is also demonstrated to resolve largely overlapping fluorophores, as demonstrated by the 3D fluorescence hyperspectral reconstruction of a dual‐labeled mouse thymus gland sample and the ability to distinguish tumorous and normal tissues of an unlabeled mouse intestine sample.
Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro
Authors: Tong Xishuai , Gu Jianhong , Song Ruilong , Wang Dong , Sun Ziqiang , Sui Chen , Zhang Chuang , Liu Xuezhong , Bian Jianchun , Liu Zongping
Published: September 2018

Osteoclasts are highly differentiated terminal cells formed by fusion of hematopoietic stem cells. Previously, osteoprotegerin (OPG) inhibit osteoclast differentiation and bone resorption by blocking receptor activator of nuclear factor‐κB ligand (RANKL) binding to RANK indirect mechanism. Furthermore, autophagy plays an important role during osteoclast differentiation and function. However, whether autophagy is involved in OPG‐inhibited osteoclast formation and bone resorption is not known. To elucidate the role of autophagy in OPG‐inhibited osteoclast differentiation and bone resorption, we used primary osteoclast derived from mice bone marrow monocytes/macrophages (BMM) by induced M‐CSF and RANKL. The results showed that autophagy‐related proteins expression were upregulated; tartrate‐resistant acid phosphatase‐positive osteoclast number and bone resorption activity were decreased; LC3 puncta and autophagosomes number were increased and activated AMPK/mTOR/p70S6K signaling pathway. In addition, chloroquine (as the autophagy/lysosome inhibitor, CQ) or rapamycin (as the autophagy/lysosome inhibitor, Rap) attenuated osteoclast differentiation and bone resorption activity by OPG treatment via AMPK/mTOR/p70S6K signaling pathway. Our data demonstrated that autophagy plays a critical role in OPG inhibiting osteoclast differentiation and bone resorption via AMPK/mTOR/p70S6K signaling pathway in vitro.
MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells
Authors: Sun Maokun , Guo Shuai , Yao Jie , Xiao Yilei , Sun Ruili , Ma Wenyi , Dong Zhaogang
Published: September 2018

Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA‐125a (miR‐125a) has been demonstrated to be implicated in various cancers. However, the functional role of miR‐125a in RCC remains largely unclear. This study was aimed to investigate the functional role of miR‐125a and the expression relevance of signal transducers and activators of transcription 3 (STAT3) with hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR‐125a was downexpressed in 786‐O cells, and examined transfected efficiency. According to functional assay, overexpression of miR‐125a inhibited cell migration and cell invasion, but no obvious effect was observed on cell proliferation. The luciferase activity assay showed that miR‐125a could directly target STAT3 3′‐untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR) assay and Western blot analysis demonstrated that miR‐125a could inhibit STAT3 expression at both messenger RNA and protein levels. Furthermore, the combination sites between STAT3 and HAS1 were predicted by prediction of transcription factor binding sites database analysis. The expression of STAT3 was correlated with HAS1 expression, exemplified by the same tendency detected by qPCR assay. Taken together, our results preliminarily demonstrate that miR‐125a could constrain cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting STAT3. It is likely to facilitate a better understanding of the regulation mechanisms of miR‐125a in RCC.
LncRNA NBR2 inhibits epithelial‐mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells
Authors: Cai Weiliang , Wu Bowen , Li Zhizhong , He Peiheng , Wang Biao , Cai Anlie , Zhang Xiping
Published: September 2018

Long noncoding RNAs (lncRNAs) have been identified to have increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. Recent studies have demonstrated that lncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is decreased in several cancers; however, the role of NBR2 in the development of osteosarcoma has not been elucidated. In our study, we found that NBR2 expression was downregulated in osteosarcoma tissues, and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall survival time compared with those with higher NBR2 expression. NBR2 overexpression inhibited osteosarcoma cell proliferation, invasion, and migration but did not increase apoptosis. Furthermore, RNA‐binding protein immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein. Furthermore, overexpression of Notch1 in NBR2‐overexpressing osteosarcoma cells reversed the effects of NBR2 on cell proliferation, invasion, migration, and epithelial‐mesenchymal transition. The in vivo results showed that NBR2 overexpression inhibited tumor growth in nude mice that were inoculated with osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA) expression of Notch1, N‐cadherin, and vimentin and increased the mRNA expression of E‐cadherin in the tumor tissues. These data indicated that NBR2 served as a tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell proliferation, invasion, and migration. The current study provides a novel insight and treatment strategy for osteosarcoma.
Mitochondrial dynamic alterations regulate melanoma cell progression
Authors: Dal Yontem Fulya , Kim Sun‐Hee , Ding Zhen , Grimm Elizabeth , Ekmekcioglu Suhendan , Akcakaya Handan
Published: September 2018

Research on mitochondrial fusion and fission (mitochondrial dynamics) has gained much attention in recent years, as it is important for understanding many biological processes, including the maintenance of mitochondrial functions, apoptosis, and cancer. The rate of mitochondrial biosynthesis and degradation can affect various aspects of tumor progression. However, the role of mitochondrial dynamics in melanoma progression remains controversial and requires a mechanistic understanding to target the altered metabolism of cancer cells. Therefore, in our study, we disrupted mitochondrial fission with mdivi‐1, the reported inhibitor of dynamin related protein 1 (Drp1), and knocked down Drp1 and Mfn2 to evaluate the effects of mitochondrial dynamic alterations on melanoma cell progression. Our confocal study results showed that mitochondrial fission was inhibited both in mdivi‐1 and in Drp1 knockdown cells and, in parallel, mitochondrial fusion was induced. We also found that mitochondrial fission inhibition by mdivi‐1 induced cell death in melanoma cells. However, silencing Drp1 and Mfn2 did not affect cell viability, but enhanced melanoma cell migration. We further show that dysregulated mitochondrial fusion by Mfn2 knockdowns suppressed the oxygen consumption rate of melanoma cells. Together, our findings suggest that mitochondrial dynamic alterations regulate melanoma cell migration and progression.
PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India: A retrospective study
Authors: Venkatesh Thejaswini , Shetty Abhishek , Chakraborti Shrijeet , Suresh Padmanaban S.
Published: September 2018

Protein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3 (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and colorectal cancers. Previous studies have documented that PTPH1‐associated breast cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors through dephosphorylation of ER and epidermal growth factor receptor, respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting the response of chemotherapeutic drugs and lack of studies on Indian breast cancer patients, the present study investigated PTPH1 protein expression and its relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of promoter in breast cancer tissues (n = 67) among Indian population by immunohistochemistry and methylation specific polymerase chain reaction. PTPH1 expression was upregulated in 58.21% (39/67) and downregulated in the rest of tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1), uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela and MCF7 cell lines. In conclusion, our data showed a strong correlation of the PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at specific CpG sites irrespective of cancer types and protein expression. Our findings underscore the clinical relevance of PTPH1 expression in Indian patients and warrant additional studies to explore the importance of ubiquitously methylated promoter at specific CpG sites in upstream of the PTPH1 gene.
Biocompatibility of alumina‐based biomaterials–A review
Authors: Rahmati Maryam , Mozafari Masoud
Published: September 2018

In today's medicine world, alumina‐based biomaterials owing to their excellent biomechanical, and biocompatibility properties play a key role in biomedical engineering. However, the literature still suffers from not having a valid database regarding the protein adsorption and subsequently cell responses to these surfaces. Proteins by adsorption on biomaterials surfaces start interpreting the construction and also arranging the biomaterials surfaces into a biological language. Hence, the main concentration of this review is on the protein adsorption and subsequently cell responses to alumina’s surface, which has a wide range biomedical applications, especially in dentistry and orthopedic applications. In the presented review article, the general principles of foreign body response mechanisms, and also the role of adsorbed proteins as key players in starting interactions between cells and alumina‐based biomaterials will be discussed in detail. In addition, the essential physicochemical, and mechanical properties of alumina surfaces which significantly impact on proteins and cells responses as well as the recent studies that have focused on the biocompatibility of alumina will be given. An in depth understanding of how the immune system interacts with the surface of alumina could prove the pivotal importance of the biocompatibility of alumina on its success in tissue engineering after implantation in body.
Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress
Authors: Zhang Tao , Chi Yanqing , Kang Yingli , Lu Hua , Niu Honglin , Liu Wei , Li Ying
Published: September 2018

Excessive generation of mitochondrial reactive oxygen species (ROS) is considered to be initiating event in the development of diabetic nephropathy (DN). Mitochondrial biosynthesis mediated by coactivator PGC‐1α and its downstream transcription factors NRF1 and TFAM may be a key target in maintaining mitochondrial function. Resveratrol (RESV), a natural polyphenolic antioxidant, is a potent SIRT1 agonist. In this study we established diabetes mouse and podocyte exposed to high glucose as in vivo and in vitro models to investigate the efficacy and mechanism of RESV on renoprotection. We found that RESV alleviated proteinuria of diabetic mice, decreased malondialdehyde content while increased Mn‐SOD activity in renal cortex, inhibited the apoptosis of glomerular podocytes and renal tubular epithelial cells, ameliorated pathological manifestations, and restored the expression of SIRT1 and PGC‐1α in renal tissues of DN mice. In podocytes exposed to high glucose, RESV inhibited excessive ROS production and apoptosis. In addition, RESV decreased mitochondrial ROS production, improved respiratory chain complex I and III activity, elevated mitochondrial membrane potential, and inhibited the release of Cyto C and Diablo in the mitochondria into the cytoplasm. Taken together, our findings suggest that RESV ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress.
Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage factors
Authors: Paolella Francesca , Manferdini Cristina , Gabusi Elena , Gambari Laura , Filardo Giuseppe , Kon Elizaveta , Mariani Erminia , Lisignoli Gina
Published: September 2018

Cell‐based therapies using adipose‐derived mesenchymal stromal cells (ADMSCs) have shown promising results for the treatment of osteoarthritis (OA). In fact, ADMSCs are now indicated as one of the most powerful cell sources through their immunomodulatory and anti‐inflammatory activities. Recently, an innovative one‐step closed device was developed to obtain microfragmented adipose tissue (MF) to avoid the need for good manufacturing practices for ADMSCs expansion while maintaining their regenerative potential. The aim of this study was to assess the mechanisms of action of MF and ADMSCs from MF (MF‐ADMSCs) on an inflammatory cell model of OA synoviocytes. We found that MF produced low levels of inflammatory factors such as interleukin 6 (IL‐6), CC‐chemokine ligand 5/receptor‐activated normal T‐cell expressed and secreted (CCL5/RANTES), CC‐chemokine ligand 2/monocyte chemoattractant protein‐1 (CCL2/MCP‐1), and CC‐chemokine ligand 3/macrophage inflammatory protein‐1α (CCL3/MIP‐1α), and a higher level only of CXC‐chemokine ligand 8/interleukin 8 compared with MF‐ADMSCs. Matrix metalloproteinase 9 (MMP‐9) degradative factor but released a lower level of its inhibitor tissue inhibitor of the metalloproteinase (TIMP‐1). MF in coculture with synoviocytes significantly induced both the metabolic activity and the release of IL‐6. In contrast, MF, not MF‐ADMSCs, partially decreased CCL5/RANTES. Moreover, MF reduced the release of both macrophage‐specific chemokines (CCL2/MCP‐1 and CCL3/MIP‐1α) and degradative marker MMP‐9. Interestingly, MF increased TIMP‐1 (the MMP‐9 inhibitor) and down‐modulated toll‐like receptor (TLR4) receptor and key molecules of NFκB pathways.

These data evidenced different effects of MF versus MF‐ADMSCs on inflamed synoviocytes. MF reduced typical macrophages markers and its potentiality by switching off macrophages activity was strictly dependent on TLR4 and NFκB signaling.
Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Wang Jin‐Cheng , Xia An‐Liang , Xu Yong , Lu Xiao‐Jie
Published: September 2018

Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.
The phosphorylation of Tudor‐SN mediated by JNK is involved in the regulation of milk protein synthesis induced by prolactin in BMECs
Authors: Zhang Sen , Qi Hao , Wen Xue‐Peng , Li Ping , Gao Xue‐Jun , Ao Jin‐Xia
Published: September 2018

Tudor staphylococcal nuclease (Tudor‐SN) is a multifunctional protein involved in a variety of cellular processes and plays a critical role in the regulation of gene expression. Recently, Tudor‐SN was found to be upregulated in mammary epithelial cells during lactation in response to prolactin, which further to regulate milk protein synthesis. However, the detailed regulatory mechanism of Tudor‐SN to milk protein still remains to be elucidated. In our study, we observed that the levels of Tudor‐SN and phosphor‐Tudor‐SN (Thr103) were both enhanced upon prolactin stimulation. Immunofluorescence assays demonstrated that prolactin treatment facilitated the nuclear transport of Tudor‐SN. Further study revealed that the phosphorylation of Tudor‐SN was depended on activated JNK. Coimmunoprecipitation assays disclosed that Tudor‐SN might be phosphorylated directly by JNK. Using gene mutation assays, we further discovered that mutation of Thr to Ala at site of 103 prevented the nuclear transport of Tudor‐SN. Thus, these results suggested the essential mechanism of the activated Tudor‐SN in milk protein regulation in response to prolactin, which may provide some new sights into improve milk protein production.
Isometric growth in the world's largest bony fishes (genus Mola)? Morphological insights from fisheries bycatch data
Authors: Phillips Natasha D. , Kubicek Lukas , Payne Nicholas L. , Harrod Chris , Eagling Lawrence E. , Carson Carol D. , Cappanera Valentina , Houghton Jonathan D.R.
Published: September 2018

For teleost fishes, the relationship between morphometric traits can provide significant insight into species life history, however gathering such data for noncommercial species can prove challenging. Here, we use data collected opportunistically from fisheries bycatch and stranding events to assess growth scaling over orders of magnitude in the ocean sunfish (genus Mola). Intriguingly, the confidence intervals for the relationship between length and mass suggests that isometric scaling is likely, a growth pattern rarely observed in fishes owing to the scaling of supportive structures. These data also enabled assessment of geometric morphometrics, which indicated that Mola sp shape varies subtly but significantly ontogenetically, with increased fin area comparative to body area as fish increase in size. More practically, total length emerged as an effective predictor for a range of morphological traits, including mass, fin lengths and surface area, which can provide vital baseline data for fisheries modeling and management.
Interreader agreement of PI‐RADS v. 2 in assessing prostate cancer with multiparametric MRI: A study using whole‐mount histology as the standard of reference
Authors: Girometti Rossano , Giannarini Gianluca , Greco Franco , Isola Miriam , Cereser Lorenzo , Como Giuseppe , Sioletic Stefano , Pizzolitto Stefano , Crestani Alessandro , Ficarra Vincenzo , Zuiani Chiara
Published: September 2018

Background

Most studies assessing interreader agreement of Prostate Imaging Reporting and Data System v. 2 (PI‐RADS v2) have used biopsy as the standard of reference, thus carrying the risk of not definitively noting all existent cancers.

Purpose

To evaluate the interreader agreement in assessing prostate cancer (PCa) of PI‐RADS v2, using whole‐mount histology as the standard of reference.

Study Type

Monocentric prospective cohort study.

Population

In all, 48 patients with biopsy‐proven PCa referred for radical prostatectomy, undergoing staging multiparametric magnetic resonance imaging (mpMRI) between May 2016 to February 2017.

Field Strength/Sequence

3.0T system using high‐resolution T2‐weighted imaging, diffusion‐weighted imaging (echo‐planar imaging with maximum b‐value 2000 sec/mm2), and dynamic contrast‐enhanced imaging (T1‐weighted high resolution isotropic volume examination; THRIVE)

Assessment

Three radiologists blinded to final histology (2–8 years of experience) analyzed mpMRI images independently, scoring imaging findings in accordance with PI‐RADS v2. On a per‐lesion basis, we calculated overall and pairwise interreader agreement in assigning PI‐RADS categories, as well as assessing malignancy with categories ≥3 or ≥4, and stage ≥pT3.

Statistical Tests

Cohen's kappa analysis of agreement.

Results

On 71 lesions found on histology, there was moderate agreement in assigning PI‐RADS categories to all cancers (k = 0.53) and clinically significant cancers (csPCa) (k = 0.47). Assessing csPCa with PI‐RADS ≥4 cutoff provided higher agreement than PI‐RADS ≥3 cutoff (k = 0.63 vs. 0.57). Interreader agreement was higher between more experienced readers, with the most experienced one achieving the highest cancer detection rate (0.73 for csPCa using category ≥4). There was substantial agreement in assessing stage ≥pT3 (k = 0.72).

Data Conclusion

We found moderate to substantial agreement in assigning the PI‐RADS v2 categories and assessing the spectrum of cancers found on whole‐mount histology, with category 4 as the most reproducible cutoff for csPCa. Readers' experience influenced interreader agreement and cancer detection rate.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:546–555.
CDC42 regulates the expression of superficial zone molecules in part through the actin cytoskeleton and myocardin‐related transcription factor‐A
Authors: Delve Elizabeth , Parreno Justin , Co Vivian , Wu Po‐Han , Chong Jasmine , Di Scipio Matteo , Kandel Rita A.
Published: September 2018

Osteoarthritis (OA) is a degenerative disease that initially manifests as loss of the superficial zone (SZ) of articular cartilage. SZ chondrocytes (SZC) differ in morphology from other chondrocytes as they are elongated and oriented parallel to the tissue surface. Proteoglycan 4 (PRG4) and tenascin C (TNC) are molecules expressed by SZC, which have been shown to be chondroprotective. Identification of the signalling pathway(s) regulating expression of SZ molecules may lead to a therapeutic target that can be used to delay or prevent the onset of OA. The hypothesis of this study is that expression of SZ molecules are regulated in part, by the CDC42‐actin‐myocardin‐related transcription factor‐A (MRTF‐A) signaling pathway. SZC from bovine metacarpal‐phalangeal joints were isolated and grown in monolayer culture. Each target in the CDC42‐actin‐MRTF‐A pathway was inhibited and the effect on cell shape, actin cytoskeleton status, and expression of PRG4 and TNC were determined. Treatment with the CDC42 inhibitor ML141 decreased PRG4 and TNC expression, and correlated with increased cell circularity and G‐/F‐actin ratio. PRG4 and TNC expression were differentially regulated by actin depolymerizing agents, latrunculin B and cytochalasin D. Chemical inhibition of MRTF‐A resulted in decreased expression of both PRG4 and TNC; however, specific knockdown by small interfering RNA only decreased expression of TNC indicating that TNC, but not PRG4, is regulated by MRTF‐A. Although PRG4 and TNC expression are both regulated by CDC42 and actin, it appears to occur through different downstream signaling pathways. Further study is required to elucidate the pathway regulating PRG4. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2421–2430, 2018.
Adherent agarose mold cultures: An in vitro platform for multi‐factorial assessment of passaged chondrocyte redifferentiation
Authors: Parreno Justin , Bianchi Vanessa J. , Sermer Corey , Regmi Suresh C. , Backstein David , Schmidt Tannin A. , Kandel Rita A.
Published: September 2018

Generating the best possible bioengineered cartilage from passaged chondrocytes requires culture condition optimization. In this study, the use of adherent agarose mold (adAM) cultures to support redifferentiation of passaged twice (P2) chondrocytes and serve as a scalable platform to assess the effect of growth factor combinations on proteoglycan accumulation by cells was examined. By 2 days in adAM culture, bovine P2 cells were partially redifferentiated as demonstrated by regression of actin‐based dedifferentiation signalling and fibroblast matrix and contractile gene expression. By day 10, aggrecan and type II collagen gene expression were significantly increased in adAM cultured cells. At day 20, a continuous layer of cartilage tissue was observed. There was no evidence of tissue contraction by P2 cells in adAM cultures. The matrix properties of the resultant tissue as well as proteoglycan 4 (PRG4) secreted by the cells were dependent on the initial cell seeding density. AdAM cultures were scalable and culture within small 3 mm diameter adAM allowed for multi‐factorial assessment of growth factors on proteoglycan accumulation by human P2 chondrocytes. Although there was a patient specific response in proteoglycan accumulation to the various cocktail combinations, the cocktail consisting of 2 ng/ml TGFβ1, 10 ng/ml FGF2, and 250 ng/ml FGF18 resulted in a consistent increase in alcian blue tissue staining. Additional studies will be required to identify the optimal conditions to bioengineer articular cartilage tissue for clinical use. However, the results to date suggest that adAM cultures may be suitable to use for high throughput assessment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2392–2405, 2018.
Asymmetry between the superior and inferior endplates is a risk factor for lumbar disc degeneration
Authors: Wang Yitao , Wang Hongli , Lv Feizhou , Ma Xiaosheng , Xia Xinlei , Jiang Jianyuan
Published: September 2018

Endplate pathology plays an important role in the development of lumbar disc degeneration. Previous research paid little attention to differences between the superior and inferior endplates as a possible risk factor for disc degeneration. The purpose of this study was to test the hypothesis that asymmetry between the superior and inferior endplates is a risk factor for the development of lumbar disc degeneration. A total of 134 patients with lumbar disc herniation (LDH) and 100 healthy adults (“Controls”) underwent magnetic resonance imaging scans. Each disc was categorized as non‐degenerated (Pfirrmann grades I–II) or degenerated (Pfirrmann grades III–V) and get the following three groups: “Degenerated LDH” discs (n = 145), “Non‐degenerated LDH” discs (n = 525) and “Non‐degenerated Control” discs (n = 500). On mid‐sagittal image, the lumbar endplate morphology could be categorized into three types: Flat, concave, and irregular. Superior and inferior endplates of a given disc were “symmetric” if both were of the same type, and “asymmetric” if they were of different types. The proportion of asymmetric endplates at L4–5 was higher in the “Degenerated LDH” discs group (47%) than in the “Non‐degenerated LDH” discs group (21%) or “Non‐degenerated Control” discs group (7%) (p < 0.05). At L5‐S1 the proportions were 73%, 55%, and 38% (p < 0.05). Asymmetry of superior and inferior endplates in the mid‐sagittal plane is a risk factor for lumbar disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2469–2475, 2018.
Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50
Authors: Weinmann Daniela , Mueller Monika , Walzer Sonja M. , Hobusch Gerhard M. , Lass Richard , Gahleitner Claudia , Viernstein Helmut , Windhager Reinhard , Toegel Stefan
Published: September 2018

This study aimed to evaluate the chondroprotective and anti‐inflammatory activity of brazilin in human osteoarthritic (OA) cartilage and chondrocytes with particular focus on the nuclear factor‐kappa B (NF‐κB) pathway. Therefore, brazilin was isolated from Caesalpinia sappan and identified using high performance liquid chromatography (HPLC). The effect of brazilin was assessed in cartilage explants treated with 10 ng/ml interleukin (IL)‐1β and 10 ng/ml tumor necrosis factor (TNF)‐α using histological and biochemical glycosaminoglycan (GAG) analyses and in primary chondrocytes treated with 10 ng/ml IL‐1β using RT‐qPCR, ELISA, and Western blot. The involvement of NF‐κB signaling was examined using a human NF‐κB signaling array and in silico pathway analysis. Brazilin was found to reduce the GAG loss from cartilage explants stimulated with IL‐1β and TNF‐α. NF‐κB pathway analysis in chondrocytes revealed NFKB1/p50 as a central player regulating the anti‐inflammatory activities of brazilin. Brazilin suppressed the IL‐1β‐mediated up‐regulation of OA markers and the induction of NFKB1/p50 in chondrocytes. In conclusion, brazilin effectively attenuates catabolic processes in human OA cartilage and chondrocytes—at least in part due to the inhibition of NFKB1/p50—which indicates a chondroprotective potential of brazilin in OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2431–2438, 2018.
High glucose‐induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells
Authors: Jiang Zengxin , Lu Wei , Zeng Qingmin , Li Defang , Ding Lei , Wu Jingping
Published: September 2018

Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high‐glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha‐lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bcl‐2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose‐ and time‐dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but decreased the level of the anti‐apoptotic protein Bcl‐2. ALA inhibited the expression of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but enhanced the expression of Bcl‐2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose‐induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose‐ and time‐dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2476–2483, 2018.
Distinguishing the Raman spectrum of polygonal serpentine
Authors: Tarling Matthew S. , Rooney Jeremy S. , Viti Cecilia , Smith Steven A.F. , Gordon Keith C.
Published: September 2018

Positively identifying serpentine mineral types is important for a wide range of disciplines in the Earth sciences and health sciences. Although Raman spectroscopy has been widely applied as a tool to distinguish four of the main serpentine minerals (i.e., antigorite, lizardite, chrysotile, and polygonal serpentine), some uncertainty remains as to whether all four varieties have unique Raman spectra. In this paper, submicron Raman spectroscopy mapping was performed directly on electron‐transparent regions of serpentine samples that were unambiguously identified by transmission electron microscopy (TEM). The increased spatial resolution of the Raman mapping technique (~370 nm), combined with the detailed characterization provided by TEM, indicates that polygonal serpentine has the same Raman spectrum as lizardite and therefore cannot be spectrally distinguished from lizardite. Furthermore, the Raman spectral profile that has previously been reported as unique to polygonal serpentine is likely to represent a mixture of chrysotile and polygonal serpentine/lizardite. To positively discriminate between lizardite and polygonal serpentine requires TEM investigation.
What makes you select a higher price option? Price–quality heuristics, cultures, and travel group compositions
Authors: Jeong Ji Youn , Crompton John L. , Hyun Sunghyup Sean
Published: September 2018

Scenarios were designed to investigate the influence of price–quality heuristics among participants from the United States, Korea, and China for different tourism and hospitality services, in different consuming situations and in different social group contexts. The results revealed that as the scenarios moved from consuming alone and with an acquaintance to with a close family member, participants in each culture had a greater propensity to select the higher price option. These tendencies were the most evident among the Korean sample, whereas the Chinese sample did not differentiate between an acquaintance and a family member, and the U.S. sample indicated mixed results.
Electrochemical corrosion kinetics of cold spray copper composite coatings in a high potential region
Authors: Rui Ding , Xiangbo Li , Jia Wang , Weihua Li , Bingjun Li , Xiao Wang , Taijiang Gui
Published: September 2018

In this paper, copper composite anticorrosion and antifouling coatings were prepared by a cold spray technique. Polarization experiments of the coatings were performed by rotating ring‐disk electrode technology at high potential. The electrochemical reaction mechanisms were proposed, and corresponding polarization kinetics models were built. Experimental results show that the copper and cuprous oxide formed corrosion microcells in the coatings, and the cuprous oxide did not alter the electrochemical reaction process of copper. In the high potential region (about 0.2–0.8 V), a CuCl film formed on the surface of the coatings was not damaged or broken down. The film played a role in corrosion protection. The currents in the high potential region increased relative to the limiting current 1. Because in the high potential region, was produced by the dissolution of the CuCl film and was oxidized to Cu2+. In addition to being oxidized to Cu2+, has the other two destinations, which were deposition as a CuCl film and diffusion to the solution bulk. The three processes were in parallel competition relations. In the limiting current 2 region, oxidation of was dominant. A rate‐controlling step of electrochemical dissolution of the coatings in the high potential region was the diffusion processes of and Cu2+. The electrochemical polarization kinetic models based on the reaction mechanisms established in this research accorded well to the experimental results. It demonstrated the rationality of polarization kinetics models and reaction mechanisms.
A modeling analysis of spatial statistical indicators of thresholds for algal blooms
Authors: Buelo C. D. , Carpenter S. R. , Pace M. L.
Published: September 2018

Predicting algal blooms both within and among aquatic ecosystems is important yet difficult because multiple factors promote and suppress blooms. Statistical indicators (e.g., variance and autocorrelation) based on time series can provide warning of transitions in diverse complex systems, including shifts from clear water to algal blooms. Analogous spatial indicators have been demonstrated with models and empirical data from vegetated terrestrial ecosystems. Here, we test the applicability of spatial indicators to algal blooms using a nutrient‐phytoplankton spatial model. We found that standard deviation and autocorrelation successfully distinguished bloom state and proximity to transitions, while skewness and kurtosis were more ambiguous. Our findings suggest certain spatial indicators are applicable to aquatic ecosystems despite dynamic physical–biological interactions that could reduce detectable signals. The growing capacity to collect spatial data on algal biomass presents an exciting opportunity for application and testing of spatial indicators to the study and management of blooms.
Correlated pitting stages of 304 stainless steel with recurrence quantification analysis of electrochemical noise
Authors: Zhang Zhen , Wu Xinqiang
Published: September 2018

Pitting corrosion behavior of 304 stainless steel (SS) in ferric chloride solutions with different concentrations was investigated by morphology observation and electrochemical noise (EN) analysis. The pitting stages were related to recurrence quantification analysis (RQA) of EN. It was found that the pitting stages of 304 SS in 0.02 and 0.3 M ferric chloride solutions mainly consist of metastable pitting and stable pitting through the morphology observation and wavelet analysis of EN. Through cluster analysis for the whole RQA variables the RQA results can accurately correlate with the pitting stages. The cluster results revealed that the metastable pitting of 304SS has high recurrence rate (RR) and determinism (DET), while the stable pitting has low RR and DET.