bluuebunny/crossref_metadata_2025 huggingface dataset:
The urban computing on the distribution of inhalable particulate matters to Smart City–based residential groups
Authors: Ma Xi'na , Zhao Jingyuan , Guo Peng
Published: August 2018

Micro‐climatic factors have provided dynamic conditions and thermal conditions for the distribution of suspended particulate matters. In this paper, courtyard‐type residential clusters built in Xi'an were selected as the research objects, through field survey, spot test, and CFD analog simulation. Plane layout physical models of the various comparable courtyard‐type residential clusters were abstracted from the perspective of urban design, reasonable numerical models were established by field test and CFD simulation, and then simulation study was conducted to the plane forms of different courtyard‐type residential clusters; the influence of different forms on the dilution and spread of atmospheric pollutants was studied quantitatively. Finally, upon overall consideration over the turbulence characteristics in the vertical direction and the distribution law of pollutants under the influence of microclimate, it was concluded that the concentration of fine PM2.5 in the space of node‐type clusters in the plane layout of courtyard‐type clusters performed worst in the comparative scope, the most favorable form was U type clusters, and the available forms were windmill‐type clusters and scattered‐vertical type clusters.
Multiscale Simulation of the Interaction and Adsorption of Ions on a Hydrophobic Graphene Surface
Authors: Chen Luohao , Guo Yanan , Xu Zhijun , Yang Xiaoning
Published: August 2018

The adsorption of ions on a graphene surface is very important to control relevant graphene‐based processes. In this work, a multiscale simulation was carried out to study the adsorption of Na+/Cl− ions on graphene by combining quantum mechanics calculations and molecular dynamics (MD) simulations. The interaction energies of the ions with graphene were computed using density functional theory (DFT). It was found that the ions show strong interaction with a graphene cluster and the overwhelming portion of the interaction energy is the ion‐π orbital interaction. The large orbital interaction can be ascribed to the two contributions arising from the ion‐induced polarization of graphene and the charge transfer between ion and graphene. Their different contribution degrees reveal that the polarization effect plays a main role on the orbital interaction for ion adsorption. Comparatively, for Na/Cl atom adsorption, the charge transfer shows large part to the orbital interaction with weak atom‐induced polarization. The obtained interaction energies were applied to develop new interaction potentials between ion and graphene, and then MD simulations were used to study the interfacial adsorption behavior of Na+/Cl− aqueous solution onto the graphene surface. Due to enhanced ion‐π interactions, Na+/Cl− cooperatively demonstrates a strong ion adsorption layer through direct contact with the hydrophobic graphene surface. Our simulation result presents a new understanding of ion‐graphene interactions.
Women on boards and efficiency in a business‐orientated environment
Authors: Uribe‐Bohorquez María Victoria , Martínez‐Ferrero Jennifer , García‐Sánchez Isabel‐María
Published: August 2018

This study proposes a new research approach to examining the relationship between board diversity in terms of gender differences and corporate performance, measured by technical efficiency. Moreover, this paper also examines the moderating role that institutional factors exert on this relationship through the cultural dimensions of the country of origin. The research questions are examined using an international sample of 2185 listed firms from 2006 to 2015, applying several truncated regression models for panel data and employing data envelopment analysis to examine efficiency as a measure of performance. This paper provides support for the assertion that female directors decrease the firm's technical efficiency; however, in more economically orientated cultures, institutional context exerts a moderating effect on the latter. The female directors of companies located in countries with higher economically orientated values adopt male stereotypes and have a significant and positive interest in improving efficiency.
Nuclear cytometry and chromatin organization
Authors: Smith Paul J. , Darzynkiewicz Zbigniew , Errington Rachel J.
Published: August 2018

The nuclear‐targeting chemical probe, for the detection and quantification of DNA within cells, has been a mainstay of cytometry—from the colorimetric Feulgen stain to smart fluorescent agents with tuned functionality. The level of nuclear structure and function at which the probe aims to readout, or indeed at which a DNA‐targeted drug acts, is shadowed by a wide range of detection modalities and analytical methods. These methods are invariably limited in terms of the resolution attainable versus the volume occupied by targeted chromatin structures. The scalar challenge arises from the need to understand the extent and different levels of compaction of genomic DNA and how such structures can be re‐modeled, reported, or even perturbed by both probes and drugs. Nuclear cytometry can report on the complex levels of chromatin order, disorder, disassembly, and even active disruption by probes and drugs. Nuclear probes can report defining features of clinical and therapeutic interest as in NETosis and other cell death processes. New cytometric approaches continue to bridge the scalar challenges of analyzing chromatin organization. Advances in super‐resolution microscopy address the resolution and depth of analysis issues in cellular systems. Typical of recent insights into chromatin organization enabled by exploiting a DNA interacting probe is ChromEM tomography (ChromEMT). ChromEMT uses the unique properties of the anthraquinone‐based cytometric dye DRAQ5™ to reveal that local and global 3D chromatin structures effect differences in compaction. The focus of this review is nuclear and chromatin cytometry, with linked reference to DNA targeting probes and drugs as exemplified by the anthracenediones.
Sclerostin is expressed in the atherosclerotic plaques of patients who undergoing carotid endarterectomy
Authors: Leto Gaetano , D'Onofrio Luca , Lucantoni Federica , Zampetti Simona , Campagna Giuseppe , Foffi Chiara , Moretti Chiara , Carlone Angela , Palermo Andrea , Leopizzi Martina , Porta Natale , Massucci Marco , Lenzi Andrea , Bertoletti Giovanni Battista , Rocca Carlo Della , Buzzetti Raffaella
Published: August 2018

Background

Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D).

Methods

This was a cross‐sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double‐staining immunochemistry, and serum SC levels were evaluated by enzyme‐linked immunosorbent assay.

Results

Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P < 0.0001) as well as in vascular smooth muscle cells (VSMCs) compared with the infiltrating macrophages (P < 0.0001). However, no significant difference in SC expression was observed between patients with and without T2D. No correlation was found between serum and immunohistochemical levels of SC; significantly increased SC serum levels were detected in males compared with females (P = 0.049).

Conclusions

We have demonstrated, for the first time, the expression of SC in VSMCs of atherosclerotic plaques, suggesting a potential role for this protein in the development of atherosclerosis. Further studies are needed to understand if the role played by SC is detrimental or protective in the atherosclerotic disease process.
Evaluating the influence of design strategies and meteorological factors on tree transpiration in bioretention suspended pavement practices
Authors: Tirpak R. Andrew , Hathaway Jon M. , Franklin Jennifer A.
Published: August 2018

Impervious surfaces, such as roads, parking areas, and buildings, found in cities throughout the world have significant impacts on urban hydrology due to increased volumes and peak flow rates of run‐off delivered to receiving waterbodies. Bioretention practices are a common stormwater control measure used to mitigate the impacts of urban run‐off. When coupled with suspended pavement systems, which provide tree roots with an uncompacted soil matrix that enhances root access to oxygen and water, engineers can design subsurface alternatives to manage urban stormwater. Two suspended pavement systems designed to function as subsurface bioretention practices were installed on the campus of the University of Tennessee, Knoxville, Tennessee, USA. Sap flow sensors using the heat ratio method were installed in two bald cypress (Taxodium distichum) trees to characterize the role of transpiration in the suspended pavement systems. Mean transpiration rates were greater when water availability was higher in the bioretention media. Regression models indicated that atmospheric vapour pressure deficit (kPa) was the most influential environmental parameter on tree transpiration and that stomatal regulation of water losses was evident when water was limiting. Findings from this study illustrate how tree transpiration rates can vary, even between individual trees of the same species, on the basis of conditions within the practice, and provide insight to practitioners on how design parameters influence fine‐scale tree–water relations in bioretention systems to maximize the contributions of transpiration on system hydrology.
Tumor‐shed antigen CA125 blocks complement‐mediated killing via suppression of C1q‐antibody binding
Authors: Kline J. Bradford , Fernando Shawn , Ross Erin N. , Grasso Luigi , Nicolaides Nicholas C.
Published: August 2018

C1q‐engagement with IgG and IgM type antibodies is the initiating step of classical complement‐mediated immunity. The tumor shed antigen CA125 has been reported to have immunosuppressive effects on host tumor responses as well as commercially approved and experimental monoclonal antibody (mAb)‐based therapeutic agents. To better understand this effect, molecular and cellular studies were carried out testing the ability of CA125 to perturb the classical complement pathway. Here, we show that patient‐derived CA125 inhibits IgG1, IgG3, and IgM‐mediated complement‐dependent cytotoxicity (CDC) by perturbing antibody‐Fc interaction with the C1q complement‐initiating protein only in those mAbs that are directly bound by CA125. This mechanism was found to impact naturally generated IgM antibodies as well as experimental and clinically approved mAbs, such as farletuzumab and rituximab, respectively. These data support a role for CA125 in humoral immune suppression and as a potential mechanism by which tumors may possibly avoid host immune responses.
Toward an Asymmetric Synthesis of Bistramide K
Authors: Bauder Claude
Published: August 2018

The bistramides family has shown antitumoral activity. More specifically bistramide K exhibits lower toxicity than its congeners. In this work, we describe a highly stereoselective and convergent synthesis of two building blocks of the marine metabolite bistramide K. Thus, we report the synthesis of fragments C1–C18 (89) and C19–C40 (81) of bistramide K. As a challenge, we have used nonracemic methyl p‐tolyl sulfoxide as unique source of chirality for the elaboration of all stereogenic centers of the natural compound.
Novel EPC1 gene fusions in endometrial stromal sarcoma
Authors: Dickson Brendan C. , Lum Amy , Swanson David , Bernardini Marcus Q. , Colgan Terrence J. , Shaw Patricia A. , Yip Stephen , Lee Cheng‐Han
Published: August 2018

Endometrial stromal sarcoma encompasses a heterogeneous group of uterine mesenchymal neoplasms, which are currently divided into low‐grade and high‐grade subtypes. Low‐grade endometrial stromal sarcoma is morphologically bland; molecularly, these tumors frequently contain JAZF1‐SUZ12, JAZF1‐PHF1, and EPC1‐PHF1 fusions. In contrast, high‐grade endometrial stromal sarcoma is characterized by morphologically undifferentiated neoplasms with high‐grade nuclear features; these tumors likewise appear to be genetically diverse with YWHAE‐NUTM2 and ZC3H7B‐BCOR representing the most frequent gene fusions. Herein, we describe two novel EPC1 fusion genes in endometrial stromal sarcoma: EPC1‐SUZ12 and EPC1‐BCOR. Both tumors were characterized be an aggressive clinical course.
The formation of the Caosiyao giant porphyry Mo deposit on the northern margin of the North China Craton: Constraints from U―Pb and Re―Os geochronology, whole‐rock geochemistry, Hf isotopes, and oxygen fugacity of the magma
Authors: Zhou Tiancheng , Zeng Qingdong , Chen Peiwen , Li Xiangzi , Cen Chaozheng , Yang Yueheng
Published: August 2018

The Caosiyao giant porphyry Mo deposit (1.76 Mt), which is the third largest such deposit in China, is located on the northern margin of the North China Craton and associated with the Caosiyao intrusive complex that was emplaced in Archaean metamorphic rocks. The intrusive complex consists of monzogranite and coarse‐, medium‐, and fine‐grained granite porphyries that yield U―Pb ages of 148.5 ± 1.2, 146.4 ± 1.0, 144.6 ± 1.0, and 142.8 ± 3.2 Ma, respectively. Four molybdenite Re―Os model ages range from 143.1 ± 2.4 to 145.3 ± 2.1 Ma, which are consistent with the U―Pb ages for the igneous complex. The geochronological data indicate that the multistage magmatic‐hydrothermal processes were important in the formation of the Caosiyao giant deposit. The rocks of the Caosiyao granitic complex have high contents of silica (SiO2 = 71.7–75.6 wt.%) and total alkalis (mostly K2O + Na2O > 8 wt.%), low contents of CaO and MgO, and exhibit peraluminous high‐K calc‐alkaline to shoshonitic affinities. They are enriched in large‐ion lithophile elements (e.g., K, Rb, U, and Th) and light REEs and depleted in Eu, Ba, Sr, Nb, P, and Ti. The geochemical characteristics indicate advanced fractional crystallization and that the rocks are strongly fractionated I‐type granites. The negative Hf isotopic compositions of the granitic rocks, combined with old two‐stage Hf model ages, indicate the magmas were derived from partial melting of the ancient lower crust of the North China Craton. All the intrusive rocks in the complex have relatively high Ce4+/Ce3+ ratios and oxygen fugacity, which would have facilitated Mo extraction into the melts owing to the much higher solubility of S as sulphate (SO42−) than sulphide (S2−). The magma crystallization temperatures decreased from 882°C to 770°C as the magma evolved. The multistage magmatic‐hydrothermal processes, and the prolonged fractional crystallization, combined with high magma oxygen fugacity are the key factors to form the Caosiyao giant Mo deposit. The tectonic setting of deposit formation was one of extension related to rollback of the subducting Palaeo‐Pacific Plate during the Late Jurassic to Early Cretaceous.
EarlyCretaceous adakitic granitoids from theZhijiazhuang skarn iron deposit,NorthTaihangMountain,China: Implications for petrogenesis and metallogenesis associated with craton destruction
Authors: Yang Fan , Santosh M. , Kim Sung Won , Zhou Hongying , Xue Fei
Published: August 2018

The North Taihang Mountain region located within the Trans‐North China Orogen is one of the major Mesozoic metallogenic belts in the North China Craton and carries varied polymetallic mineralization associated with multiple magmatic pulses. Here, we investigate the Zhijiazhuang skarn iron deposit from this region through petrological, geochemical, zircon U–Pb geochronological and Lu–Hf isotopic studies of the associated granitoids to constrain the ages, petrogenesis, and process of mineralization. Zircon U–Pb dating shows multiple pulses of magmatism with three major peaks at 134, 129, and 125 Ma as well as some scattered spot ages of 121, 118, and 112 Ma consistent with regional multistage magmatic events during the Early Cretaceous. Zircon Hf data display negative εHf(t) values from −21.7 to −7.8 and two‐stage crustal model ages (TDMC) in the range of 1,680–2,560 Ma, indicating magma derivation from reworking of late Neoarchean to early Paleoproterozoic crustal materials possibly with minor lithospheric mantle input. Geochemical data indicate I‐type adakitic signature for the intrusion, suggesting the involvement of subduction‐related components. The adakitic rocks identified in this study originated from a mixture of crustal and lithospheric mantle components followed by upper crustal fractional crystallization. Collectively, the data suggest that the granitoids were formed by interaction of crust–mantle materials through partial melting of a thickened or delaminated lower continental crust and lithospheric mantle corresponding to the peak event of lithospheric thinning and craton destruction of the North China Craton. The tectonics is correlated with the westward subduction of the Paleo‐Pacific Plate. Combined with information from previous studies associated with porphyry–skarn‐type deposits in the whole Taihang Mountain region, we correlate the multiple phases of magmatism and mineralization of the deposit to the peak event of lithospheric thinning and destruction of the North China Craton, and the Zhijiazhuang skarn iron deposit was likely generated by the interaction of magmas and fluids with the dolomitic wall rocks.
Immunochemotherapeutic increase of peripheral absolute monocyte count predicts interstitial pneumonia in lymphoma patients
Authors: Lang Mingxiao , Yu Jingwei , Wang Xianhuo , Song Zheng , Li Lanfang , Qiu Lihua , Zhang Huilai
Published: August 2018

Interstitial pneumonia (IP) is one of the potentially fatal adverse events for lymphoma patients undergoing immunochemotherapy. However, the risk factors and predictive markers remain unclear for this complication. This retrospective study aims to explore whether the change of absolute monocyte count (AMC) during immunochemotherapy is correlated with IP occurrence and progression. A total of 500 lymphoma patients receiving immunochemotherapy from 2014 to 2016 were enrolled in this investigation. Interstitial pneumonia was generally diagnosed as diffused pulmonary interstitial infiltrates on computed tomography images in conjunction with respiratory symptoms or pulmonary function test, which is also adopted as a diagnosing tool of IP in this study. Among the total 500 participating patients, 40 patients were diagnosed as IP, which account for 8% of the total subjects. The median number of chemotherapy cycles for those patients prior to IP occurrence is 4. This research suggests that the increase of peripheral AMC over 0.565 × 109/L after 2 cycles of immunochemotherapy is a great potential to develop IP. Using the method of multivariate analysis, lymphoma lung involvement and high AMC after 2 cycles of immunochemotherapy were identified as independent risk factors for IP. Most IP patients with sustained AMC elevation (>0.575 × 109/L at IP onset) accompanied severe pulmonary symptoms, while those with AMC fall‐back might tolerate subsequent immunochemotherapy. Thus, this study concludes that early increase of AMC during immunochemotherapy in lymphoma patients with lung involvement suggested a great potential to develop IP. Dynamic changes in AMC may serve as a predictive marker for IP severity and a guide for treatment adjustment for both tumor and pulmonary injuries.
Risk-based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools
Authors: Dingemans Milou ML , Baken Kirsten A , van der Oost Ron , Schriks Merijn , van Wezel Annemarie P
Published: August 2018

A plethora of in vitro bioassays are developed in the context of chemical risk assessment and clinical diagnostics to test effects on different biological processes. Such assays can also be implemented in effect-based monitoring (EBM) of (drinking) water quality alongside chemical analyses. Effects-based monitoring can provide insight into risks for the environment and human health associated with exposure to (unknown) complex, low-level mixtures of micropollutants, which fits in the risk-based approach that was recently introduced in the European Drinking Water Directive. Some challenges remain, in particular those related to selection and interpretation of bioassays. For water quality assessment, carcinogenesis, adverse effects on reproduction and development, effects on xenobiotic metabolism, modulation of hormone systems, DNA reactivity, and adaptive stress responses are considered the most relevant toxicological endpoints. An evaluation procedure of the applicability and performance of in vitro bioassays for water quality monitoring, based on existing information, has been developed, which can be expanded with guidelines for experimental evaluations. In addition, a methodology for the interpretation of in vitro monitoring data is required, because the sensitivity of specific in vitro bioassays in combination with sample concentration may lead to responses of chemicals (far) below exposure concentrations that are relevant for human health effects. Different approaches are proposed to derive effect-based trigger values (EBTs), including EBTs based on (1) relative ecotoxicity potency, (2) health-based threshold values for chronic exposure in humans and kinetics of reference chemicals, and (3) read-across from (drinking) water guideline values. Effects-based trigger values need to be chosen carefully in order to be sufficiently but not overly conservative to indicate potential health effects. Consensus on the crucial steps in the selection and interpretation of in vitro bioassay data will facilitate implementation and legal embedding in the context of water quality monitoring of such assays in EBM strategies. Integr Environ Assess Manag 2019;15:126–134. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Controllable Coordination Self‐Assembly Based on Flexibility of Ligands: Synthesis of Supramolecular Assemblies and Stimuli‐Driven Structural Transformations
Authors: Hou Haiyang , Zhou Kang , Jiang Feilong , Chen QiHui , Hong Maochun
Published: August 2018

Coordination self‐assemblies have attracted more and more attentions from chemists because of their beautiful structures and wide applications, and a number of excellent reviews that focus on either synthesis or application have been published. This paper will hightlight how to controllablly construct supramolecular assemblies based on flexibility of ligands driven by different external stimuli. Herein, not only various discrete metal‐organic aggregates including M2L2 type metallocycles, M2L4/M2L6/M3L2/M6L4/M6L8 type metallocages have been prepared, but also many well‐organized ensembles based on such new‐formed discrete aggretates have been further assembled driven by suitable external stimuli. Also, controllable self‐assembly processes accompanied with structure changes have been developed. It is expected that this paper will provide a potential strategy for developing novel coordination assemblies that can be comparable to biomacromolecules from organism.
A Case Series Study of Odontoid Fracture in the Elderly: A Severe Fracture Occurring Most Frequently in Osteoporotic Subjects
Authors: Natella Lauren , Bronsard Nicolas , Allia Jeremy , Hekayem Laurent , Euller‐Ziegler Liana , De Peretti Fernand , Breuil Véronique
Published: August 2018

The WHO definition of osteoporosis excludes cervical fractures. Recent studies suggest that atraumatic odontoid fractures (OF) may be favored by osteoporosis but global bone status for osteoporosis diagnosis has not been described. We present a case series of patients >65 years old hospitalized for low‐energy OF who had an evaluation of their bone status within 3 months after fracture, including clinical risk factors of osteoporosis, bone mineral density (BMD), vertebral fracture assessment (VFA) by dual X‐ray absorptiometry, and laboratory tests. Osteoporosis was defined as a T‐score ≤ −2.5 on at least one site, or a bone fragility fracture associated with a T‐score ≤ −1 at one site. Thirty‐three patients were hospitalized for OF, 30 of them as a consequence of a low‐energy impact: 20 women and 10 men (mean age: 85 years). Eight patients died before bone evaluation, four refused, and six were lost to follow‐up. Twelve patients were included: 11 women and one man (mean age: 83.8 years). Ten out of twelve patients fulfilled diagnostic criteria of osteoporosis, including eight with previous osteoporotic fractures (six severe fractures). Eight fulfilled specific treatment of osteoporosis criteria, but only two were treated. The mean follow‐up period was 12.2 ± 4.1 months. Prior to OF occurrence, all lived at home and were independent; at the time of discharge, six went to a nursing home. At 3 months of follow‐up (n = 10), one was dead and nine lived at home. At 12 months (n = 9), two were dead and seven lived at home. This study provides for the first time a classical evaluation of osteoporotic status for low‐energy OF in the elderly and shows that it occurs in osteoporotic subjects. These preliminary results require larger‐scale studies to determine whether OF could be considered as a severe osteoporotic fracture. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Adenosine diphosphate–sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators
Authors: Chen Xiaobin , Xiao Bolin , Yang Mei , Chen Meifang , Xiao Zhilin
Published: August 2018

Extracellular adenosine diphosphate (ADP) mediates a wide range of physiological effects as an extracellular signaling molecule, including platelet aggregation, vascular tone, cell proliferation, and apoptosis by interacting with plasma membrane P2 receptors. However, the effect of ADP on cell proliferation was contradictory. In this study, we found that ADP significantly inhibited cell proliferation of human umbilical vein endothelial cells at high concentrations (50 to 100 µM). Treatment with ADP did not induce cell apoptosis but instead induced cell cycle arrest in the S phase, which may be partly due to the downregulation of cyclin B1. The inhibition of cell proliferation was blocked by suramin, a nonspecific antagonist of the P2 receptors, and high concentrations of ADP significantly upregulated the messenger RNA (mRNA) and protein expression of P2Y11 in endothelial cells. Moreover, the downregulation of P2Y11 by RNA interference reversed the inhibition of cell proliferation. In addition, ADP (100 µM) can induce the formation of cytosolic autophagy in endothelial cells and a rapid phosphorylation of extracellular signal regulated kinase (ERK) 1/2, which is a canonical signal molecule downstream of P2Y receptors, accompanied by a mRNA expression of proinflammatory cytokines such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Taken together, our study excludes a mechanism for extracellular ADP impairing endothelial cells proliferation via P2Y11 receptor by downregulating cyclin B1 and arresting cell cycle at the S phase, besides, ADP induces cell autophagy and mRNA expression of inflammatory cytokines, whether it is mediated by Erk signaling pathways needs further studies to confirm.
The “mechanostat” principle in cell differentiation. The osteochondroprogenitor paradigm
Authors: Tyrovola Joanna B.
Published: August 2018

The “mechanostat” principle may be depicted as an oscillating signal of a signaling molecule, in which the amplitude, frequency, cumulative level, delay, and duration of the curve encode the information for concrete cellular responses and biological activities. When the oscillating signal is kept sustained (present delay), cell exit may be performed, whereas when the oscillating signal remains robust, cell proliferation may take place. B‐catenin–Wnt signaling pathway has a key role in the differentiation of osteochondroprogenitor cells. Sustained downregulation of the β‐catenin–Wnt pathway forces osteochondroprogenitors to a chondrogenic fate instead of an osteoblastic one. Other signaling, for example, bone morphogenetic protein and Notch signaling pathways interact with the Wnt pathway. The crosstalk between biochemical and mechanical stimuli produces the final information that leads to the final cell fate decisions, through the “mechanostat” principle.
Human umbilical cord tissue stem cells and neuronal lineages in an injectable caffeic acid–bioconjugated gelatin hydrogel for transplantation
Authors: Subbarayan Rajasekaran , Girija Dinesh Murugan , Rao Suresh Ranga
Published: August 2018

Present‐day scaffolds are useful in cell therapy to a reasonable extent, but in pursuit of improvising the scaffold to improve the outcome, we tested a new injectable caffeic acid–bioconjugated gelatin hydrogel scaffold (CBGH; with tunable stiffness −10%). Two‐dimensional (2D) form of human umbilical cord tissue‐derived mesenchymal stem cells (HUCMSCs) culture performed based on our previously reported methods and characterized by using multipotent and pluripotent analysis. In addition, neurogenesis was induced in the presence of retinoic acid or neural growth factor or epidermal growth factor categorized by neuronal markers. The viability, proliferation rate, and vascular endothelial growth factor expression of HUCMSCs increased significantly in the CBGH scaffold. In addition, there was an increase in CD90 and TRA‐1‐81 phenotypic expressions and SOX‐2, MAP‐2, TAU, NeuN, and NF, which confirmed the neurogenesis of encapsulated HUCMSCs. Topographical elucidation by scanning electron microscopy data showed that the HUCMSCs proliferated and migrated inside the construct. Hematoxylin and eosin staining demonstrated a more viable structural pattern and cresyl violet staining showed the Nissl synthesis, confirming the presence of functional neurons in the encapsulated form. The molecular‐level analysis further substantiated that HUCMSCs cultured in CBGH expressed significantly greater upregulation of stemness, neuronal genes, and protein expression compared with the adherent culture. Correspondingly, this is the first time that we have measured the fluorescence intensity variation of the HUCMSCs‐stained cell segmentation process using customized MATLAB code execution to reduce the background noise and autofluorescence. We conclude that this novel CBGH scaffold increases the viability, proliferation, stemness, and also neuronal transdifferentiation of HUCMSCs in a three‐dimensional culture than the 2D plastic adherent culture.
The metabolic and molecular mechanisms of hyperammonaemia‐ and hyperethanolaemia‐induced protein catabolism in skeletal muscle cells
Authors: Crossland Hannah , Smith Kenneth , Atherton Philip J. , Wilkinson Daniel J.
Published: August 2018

Hyperammonaemia and hyperethanolaemia are thought to be driving factors behind skeletal muscle myopathy in liver disease, that is, cirrhosis. Despite this, the singular and combined impacts of ethanol‐ and ammonia‐induced protein catabolism are poorly defined. As such, we aimed to dissect out the effects of ammonia and ethanol on muscle catabolism. Murine C2C12 myotubes were treated with ammonium acetate (10 mM) and ethanol (100 mM) either alone or in combination for 4 hr and/or 24 hr. Myotube diameter, muscle protein synthesis and anabolic and catabolic signalling pathways were assessed. In separate experiments, cells were cotreated with selected inhibitors of protein breakdown to assess the importance of proteolytic pathways in protein loss with ammonia and ethanol. Ammonia and ethanol in combination resulted in a reduction in myotube width and total protein content, which was greater than the reduction observed with ammonia alone. Both ammonia and ethanol caused reductions in protein synthesis, as assessed by puromycin incorporation. There was also evidence of impairments in regulation of protein translation, and increased protein expression of markers of muscle protein breakdown. Myotube protein loss with ammonia plus ethanol was not affected by autophagy inhibition, but was completely prevented by proteasome inhibition. Thus, combined ammonia and ethanol incubation of C2C12 myotubes exacerbated myotube atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Ubiquitin proteasome‐mediated protein breakdown appears to play an important role in myotube protein loss with ethanol and ammonia.
Downregulated microRNA‐340‐5p promotes proliferation and inhibits apoptosis of chondrocytes in osteoarthritis mice through inhibiting the extracellular signal‐regulated kinase signaling pathway by negatively targeting the FMOD gene
Authors: Zhang Weikai , Cheng Peng , Hu Weihua , Yin Weifeng , Guo Fengjing , Chen Anmin , Huang Hui
Published: August 2018

Purpose

Osteoarthritis (OA) is a degenerative joint disease that leads to the destruction of joint function. The aim of this study is to investigate the effects of microRNA‐340‐5p (miR‐340‐5p) and its target gene, FMOD, on the proliferation and apoptosis of chondrocytes in mice with OA through the extracellular signal‐regulated kinase (ERK) signaling pathway.

Materials

Twenty healthy C57BL/6J mice aged 15 months with a weight of 50 ± 2 g were selected. Ten mice were treated using a unilateral knee anterior cruciate ligament transection as well as a medial meniscectomy to establish the OA model. Besides, another 10 mice were used as the control group.

Methods

A reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were used to examine the expressions of related genes in cells of each group. A 3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide assay and flow cytometry were also conducted to evaluate the cell function after transfection had been completed.

Results

The expressions of fibromodulin (FMOD), type II collagen (Col II), B‐cell lymphoma‐2 (Bcl‐2), sex‐determining region of Y chromosome (SRY)‐related high‐mobility group‐box gene 9 (Sox9), and proliferating cell nuclear antigen (PCNA) were decreased, whereas the expressions of miR‐340‐5p, runt‐related transcription factor‐2 (Runx2), Bcl‐2‐associated X protein (Bax), and ERK1/2 were elevated in the OA mice. Downregulation of miR‐340‐5p and upregulation of FMOD decreased the expressions of Runx2, Bax, and ERK1/2, and cell apoptosis of chondrocytes, and increased the expressions of FMOD, Col II, Bcl‐2, Sox9, and PCNA, and cell proliferation.

Conclusion

This study suggests that downregulation of miR‐340‐5p plays a role in promoting cell proliferation and suppressing cell apoptosis of chondrocytes in OA mice through inhibition of the ERK signaling pathway via the FMOD gene.
Retracted: MicroRNA‐150 contributes to ischemic stroke through its effect on cerebral cortical neuron survival and function by inhibiting ERK1/2 axis via Mal
Authors: Lv Hui , Li Jie , Che Yu‐Qin
Published: August 2018

Ischemic stroke, caused by the blockage of blood supply, is a major cause of death worldwide. For identifying potential candidates, we explored the effects microRNA‐150 (miR‐150) has on ischemic stroke and its underlying mechanism by developing a stable middle cerebral artery occlusion (MCAO) rat model. Gene expression microarray analysis was performed to screen differentially expressed genes associated with MCAO. We evaluated the expression of miR‐150 and Mal and the status of ERK1/2 axis in the brain tissues of MCAO rats. Then the cerebral cortical neurons (CCNs) were obtained and introduced with elevated or suppressed miR‐150 or silenced Mal to validate regulatory mechanisms for miR‐150 governing Mal in vitro. The relationship between miR‐150 and Mal was verified by dual luciferase reporter gene assay. Besides, cell growth and apoptosis of CCNs were detected by means of MTT assay and flow cytometry analyses. We identified Mal as a downregulated gene in MCAO, based on the microarray data of GSE16561. MiR‐150 was over‐expressed and negatively targeted Mal in the brain tissues obtained from MCAO rats and their CCNs. Increasing miR‐150 blocked the ERK1/2 axis, resulting in an inhibited cell growth of CNNs but an enhanced apoptosis. Furthermore, MiR‐150 inhibition was observed to have effects on CNNs as opposed to those inhibited by miR‐150 promotion. The key findings of this study support the notion that miR‐150 under‐expression‐mediated direct promotion of Mal protects CNN functions through the activation of the ERK1/2 axis, and underscore the concept that miR‐150 may represent a novel pharmacological target for ischemic stroke intervention.
Role and translational implication of galectins in arthritis pathophysiology and treatment: A systematic literature review
Authors: Salamanna Francesca , Veronesi Francesca , Frizziero Antonio , Fini Milena
Published: August 2018

Galectins are members of the animal lectin family that bind to the β‐galactoside‐containing carbohydrate moieties of glycoconjugates. They seem to have an important role in the pathophysiology of several diseases, including arthritis. Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic conditions with few or no available therapies. In this context, galectins could provide a novel opportunity, but the precise role and mechanism of their involvement in arthritis are still not fully understood. This descriptive systematic literature review summarizes in vitro, in vivo, and clinical studies that analyzed and examined the role and mechanism of action of galectins in arthritis to highlight and clarify their possible translation implication. This review yielded promising evidence that individual galectins, in particular galectin‐1, ‐3, and ‐9, could play positive or negative roles in the pathogenesis of arthritis, especially in RA and OA. It also emphasized the cell‐dependent role of these galectins. This is particularly true for galectin‐1, which was shown to have a protective anti‐inflammatory role in RA, while it seemed to be associated with cartilage degeneration in OA. In summary, this review underlined that manipulation of certain galectins can suppress or aggravate disease symptoms in arthritis animal models, demonstrating the therapeutic potential of galectins for the treatment of RA and OA. Nevertheless, despite the fact that galectin therapy and therapies acting on galectin expression seem to be an interesting and important opportunity for research, we highlighted that further investigation is necessary to carefully evaluate their potential clinical implications in arthritis.
Src mediates TGF‐β‐induced intraocular pressure elevation in glaucoma
Authors: Tsukamoto Teruhisa , Kajiwara Kentaro , Nada Shigeyuki , Okada Masato
Published: August 2018

Glaucoma, a progressive and irreversible optic neuropathy, is one of the leading causes of vision impairment worldwide. Elevation of intraocular pressure (IOP) due to transforming growth factor‐β (TGF‐β)‐induced dysfunction of the trabecular meshwork is a risk factor for glaucoma, but the underlying molecular mechanisms remain elusive. Here, we show that Src kinase is involved in TGF‐β‐induced IOP elevation. We observed that dasatinib, a potent Src inhibitor, suppressed TGF‐β2‐induced IOP in rat eyes. Mechanistic analyses in human trabecular meshwork cells showed that TGF‐β2 activated Src signaling and concomitantly increased cytoskeletal remodeling, cell adhesion, and extracellular matrix (ECM) accumulation. Src was activated via TGF‐β2‐induced upregulation of the Src scaffolding protein CasL, which mediates the assembly of focal adhesions, cytoskeletal remodeling, and ECM deposition. Activation of Src suppressed the expression of tissue plasminogen activator, thereby attenuating ECM degradation. Furthermore, the Src inhibitor ameliorated TGF‐β2‐induced changes in the contractile and adhesive characteristics of trabecular meshwork cells, and ECM deposition. These findings underscore the crucial role of Src activity in TGF‐β‐induced IOP elevation and identify Src signaling as a potential therapeutic target in glaucoma.
The evolving role of analytics to determine hospital risk management staffing
Authors: Felton Kenneth W. , Howard Chrystina M. , Osgood Elizabeth
Published: August 2018

This article presents the evolution of an independently developed research project to gather time data from hospital and health care system risk managers to establish an objective, justifiable means of determining necessary staffing levels to support risk management activities and department functions. The authors relied on the data submitted by study participants and did not independently audit the numbers provided.
Rapid high‐resolution T1 mapping using a highly accelerated radial steady‐state free‐precession technique
Authors: Li Zhitao , Bilgin Ali , Johnson Kevin , Galons Jean‐Philippe , Vedantham Srinivasan , Martin Diego R. , Altbach Maria I.
Published: August 2018

Background

T1 mapping is often used in some clinical protocols. Existing techniques are limited in slice coverage, and/or spatial‐temporal resolution, or require long acquisitions. Here we present a multi‐slice inversion‐recovery (IR) radial steady‐state free precession (radSSFP) pulse sequence combined with a principal component (PC) based reconstruction that overcomes these limitations.

Purpose

To develop a fast technique for multi‐slice high‐resolution T1 mapping.

Study Type

Technical efficacy study done prospectively.

Phantom/Subjects

IR‐radSSFP was tested in phantoms, five healthy volunteers, and four patients with abdominal lesions.

Field Strength/Sequence

IR‐radSSFP was implemented at 3T.

Assessment

Computer simulations were performed to optimize the flip angle for T1 estimation; testing was done in phantoms using as reference an IR spin‐echo pulse sequence. T1 mapping with IR‐radSSFP was also assessed in vivo (brain and abdomen) and T1 values were compared with literature. T1 maps were also compared with a radial IR‐FLASH technique.

Statistical Tests

A two‐tailed t‐test was used to compare T1 values in phantoms. A repeatability study was carried out in vivo using Bland‐Altman analysis.

Results

Simulations and phantom experiments showed that a flip angle of 20˚ was optimal for T1 mapping. When comparing single to multi‐slice experiments in phantoms there were no significant differences between the means T1 values (P = 0.0475). In vivo results show that T1 maps with spatial resolution as high as 0.69 mm × 0.69 mm × 2.00 mm (brain) and 0.83 mm × 0.83 mm × 3.00 mm (abdomen) can be generated for 84 brain slices in 3 min and 10 abdominal slices in a breath‐hold; T1 values were comparable to those reported in literature. The coefficients of variation from the repeatability study were 1.7% for brain and 2.5–2.7% in the abdomen.

Data Conclusion

A multi‐slice IR‐radSSFP technique combined with a PC‐based reconstruction was demonstrated for higher resolution T1 mapping. This technique is fast, motion‐insensitive and yields repeatable T1 values comparable to those in literature.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:239–252.
10‐Min 3D Turbo Spin Echo MRI of the Knee in Children: Arthroscopy‐Validated Accuracy for the Diagnosis of Internal Derangement
Authors: Fritz Jan , Ahlawat Shivani , Fritz Benjamin , Thawait Gaurav K. , Stern Steven E. , Raithel Esther , Klyce Walter , Lee Rushyuan J.
Published: August 2018

Background

Ten‐minute MRI of the pediatric knee can add value through increased cost‐effectiveness and decreased sedation needs but requires validation of its clinical efficacy.

Purpose

To determine the arthroscopy‐based diagnostic accuracy and interreader reliability of 10‐min 3D Controlled Aliasing In Parallel Imaging Results In Higher Acceleration (CAIPIRINHA) turbo spin echo (TSE) MRI with two isotropic pulse sequences for the diagnosis of internal derangement in children with painful knee conditions.

Study Type

Prospective.

Subjects

Sixty children.

Field Strength/Sequence

3T, gradient echo‐based scout with automatic anatomical landmark recognition and plane prescription, 3D CAIPIRINHA SPACE TSE.

Assessment

Three fellowship‐trained musculoskeletal radiologists evaluated the MRI studies independently and resolved discrepancies through consensus. Outcome variables included image quality, motion artifacts, meniscal abnormalities, anterior and posterior cruciate ligament tears, and cartilage lesions. Arthroscopic surgery served as the standard of reference, which was performed after 37 (range, 1–143) days post‐MRI.

Statistical Tests

Diagnostic accuracy analysis of MRI with arthroscopic surgery as the standard of reference. Reliability analysis through calculation of interreader agreements with kappa statistics.

Results

All studies were suitable for diagnostic interpretation with good‐to‐very‐good image quality ratings and little‐to‐no motion degradation ratings in the majority of cases. The sensitivities/specificities/accuracies of 3D CAIPIRINHA TSE MRI were 0.93/0.96/0.94 for 15/60 (25%) medial meniscal tears, 0.95/0.92/0.94 for 21/60 (35%) lateral meniscal tears, 0.83/1.00/0.92 for 6/60 (17%) discoid menisci, 1.00/0.98/0.99 for 16/60 (27%) anterior cruciate ligament tears, 1.0/1.0/1.0 for 2/60 (3%) posterior cruciate ligament tears, 1.00/1.00/1.00 for 5/60 (8%) osteochondritis dissecans lesions, 0.71/0.96/0.84 for 48 (13%) defects in 360 cartilage segments, and 0.85/0.97/0.91 overall. The interreader agreements were overall good‐to‐very‐good (kappa, 0.72–1.00).

Data Conclusion

The clinical use of 10‐min 3D CAIPIRINHA TSE MRI of the knee in children with painful knee conditions yields an overall high arthroscopy‐validated diagnostic accuracy of 91% and good‐to‐very good interreader reliability for the diagnosis of internal knee derangements.

Level of Evidence: 1

Technical Efficacy: Stage 6

J. Magn. Reson. Imaging 2019;49:e139–e151.