bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel Anti-Inflammatory Properties
Authors: Carelli Stephana , Colli Mattia , Vinci Valeriano , Caviggioli Fabio , Klinger Marco , Gorio Alfredo
Published: January 2018

The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and CXCL8. Most of their production occurs in macrophages that act as scavengers of dying adipocytes. The application of an orbital mechanical force for 6–10 min at 97 g to the adipose tissue, lipoaspirated and treated according to Coleman procedures, abolishes the expression of TNF-α and stimulates the expression of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had protective and anti-inflammatory effects when applied to animal models of rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4 were also strongly augmented by mechanical activation, suggesting an effect on stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells (hADSCs), produced from activated fat, grow and differentiate normally with proper cell surface markers and chromosomal integrity, but their anti-inflammatory action is far superior compared to those mesenchymal stem cells (MSCs) obtained from lipoaspirate. The expression and release of inflammatory cytokines from THP-1 cells was totally abolished in mechanically activated adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking of adipose tissue enhances its anti-inflammatory properties, and derived MSCs maintain such enhanced activity.
Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow-Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant
Authors: Spakova Timea , Plsikova Jana , Harvanova Denisa , Lacko Marek , Stolfa Stefan , Rosocha Jan
Published: January 2018

Articular cartilage has limited capacity for natural regeneration and repair. In the present study, we evaluated kartogenin (KGN), a bioactive small heterocyclic molecule, for its effect on in vitro proliferation and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSCs) in monolayer culture and in co-culture models in vitro. OA osteochondral cylinders and hBMSCs were collected during total knee replacement. The effect of KGN on hBMSCs during 21 days of culture was monitored by real-time proliferation assay, immunofluorescence staining, histological assay, scanning electron microscopy (SEM) (imaging and multiplex enzyme-linked immunosorbent assay) ELISA assay. The rate of proliferation of hBMSCs was significantly increased by treatment with 10 µM KGN during nine days of culture. Histological and SEM analyses showed the ability of hBMSCs in the presence of KGN to colonize the surface of OA cartilage and to produce glycosaminoglycans and proteoglycans after 21 days of co-culture. KGN treated hBMSCs secreted higher concentrations of TIMPs and the secretion of pro-inflammatory molecules (MMP 13, TNF-α) were significantly suppressed in comparison with control without hBMSCs. Our preliminary results support the concept that 10 µM KGN enhances proliferation and chondrogenic differentiation of hBMSCs and suggest that KGN is a potential promoter for cell-based therapeutic application for cartilage regeneration.
Lewis Pair Catalysts in the Polymerization of Lactide and Related Cyclic Esters
Authors: Li Xinlei , Chen Changjuan , Wu Jincai
Published: January 2018

Polyesters, especially poly(lactide) (PLA), are used widely as biodegradable and biocompatible materials, yet their controllable synthesis, especially the stereoselective synthesis of polyesters, is still a challenge. Recently some excellent Lewis pair catalysts for ring-opening polymerization (ROP) of lactide and related cyclic esters have emerged. This review article will highlight the key advances in the ROP catalyzed by Lewis pair compounds with the aim of encouraging the wider application of Lewis pair catalysts in the polymerization of lactide and related cyclic esters.
Development of a Region-Specific Physiologically Based Pharmacokinetic Brain Model to Assess Hippocampus and Frontal Cortex Pharmacokinetics
Authors: Zakaria Zaril , Badhan Raj
Published: January 2018

Central nervous system drug discovery and development is hindered by the impermeable nature of the blood–brain barrier. Pharmacokinetic modeling can provide a novel approach to estimate CNS drug exposure; however, existing models do not predict temporal drug concentrations in distinct brain regions. A rat CNS physiologically based pharmacokinetic (PBPK) model was developed, incorporating brain compartments for the frontal cortex (FC), hippocampus (HC), “rest-of-brain” (ROB), and cerebrospinal fluid (CSF). Model predictions of FC and HC Cmax, tmax and AUC were within 2-fold of that reported for carbamazepine and phenytoin. The inclusion of a 30% coefficient of variation on regional brain tissue volumes, to assess the uncertainty of regional brain compartments volumes on predicted concentrations, resulted in a minimal level of sensitivity of model predictions. This model was subsequently extended to predict human brain morphine concentrations, and predicted a ROB Cmax of 21.7 ± 6.41 ng/mL when compared to “better” (10.1 ng/mL) or “worse” (29.8 ng/mL) brain tissue regions with a FC Cmax of 62.12 ± 17.32 ng/mL and a HC Cmax of 182.2 ± 51.2 ng/mL. These results indicate that this simplified regional brain PBPK model is useful for forward prediction approaches in humans for estimating regional brain drug concentrations.
Analysis of Trade-offs between Food Security and Water-Land Savings through Food Trade and Structural Changes of Virtual Water Trade in the Arab World
Authors: Lee Sang-Hyun , Mohtar Rabi H. , Yoo Seung-Hwan
Published: January 2018

Abstract. The aim of this study is to analyze the impacts of food trade on food security and water-land savings in the Arab World in terms of virtual water trade (VWT). We estimated the total volume of virtual water imported for four major crops – barley, maize, rice, and wheat – from 2000 to 2012, and assessed their impacts on water and land savings, and food security. The largest volume of virtual water was imported by Egypt (19.9 billion m3/year), followed by Saudi Arabia (13.0 billion m3/year). Accordingly, Egypt would save 13.1 billion m3 in irrigation water and 2.1 million ha of crop area through importing crops. In addition, connectivity and influence of each country in the VWT network was analyzed using degree and eigenvector centralities. The study revealed that the Arab World focused more on increasing the volume of virtual water imported during the period 2006–2012 with little attention to the expansion of connections with country exporters, which is a vulnerable expansion. This study shed light on opportunities and risks associated with VWT and its role in food security and land management in the Arab World.
Oral Pedagogy, Playful Variation, and Issues of Notation in Khmer Wedding Music
Authors: Dyer Jeffrey
Published: January 2018

This study of Khmer wedding musicians’ oral pedagogy explores tensions that arise when prescriptive notation is deployed to preserve a precarious tradition. Presenting detailed examples of the musical variation that oral pedagogy promotes, I argue that this teaching method fosters the skills musicians need to play wedding music in its ritual context. Situating my ethnographic research within broad debates over continuity and change, as well as literacy and orality, I suggest that Khmer wedding musicians have developed a “local bimusicality” and may be able to read notation generatively to produce a song’s variations, maintaining the playfulness central to this performance practice.
Negative Emotional Valence Intensity Affects Visual Target Detection in the Information Encoding Process
Authors: Takeshima Yasuhiro
Published: January 2018

Previous studies have not yet investigated sufficiently the relationship between visual processing and negative emotional valence intensity, which is the degree of a dimensional component included in emotional information. In Experiment 1, participants performed a visual search task with three valence levels: neutral (control) and high- and low-intensity negative emotional valence stimuli (both angry faces). Results indicated that response times for high-intensity negative emotional valence stimuli were shorter than low-intensity ones. In Experiment 2, participants were asked to detect a target face among successively presented faces. Facial stimuli were the same as in Experiment 1. Results revealed that accuracy was higher for angry faces than for neutral faces. However, performance did not differ as a function of negative emotional valence intensity. Overall, the task performance differences between negative emotional valence intensities were observed in visual search, but not in attentional blink. Therefore, negative emotional valence intensity likely contributes to the process of efficient visual information encoding.
Mud Volcanism in a Canyon: Morphodynamic Evolution of the Active Venere Mud Volcano and Its Interplay With Squillace Canyon, Central Mediterranean
Authors: Loher Markus , Ceramicola Silvia , Wintersteller Paul , Meinecke Gerrit , Sahling Heiko , Bohrmann Gerhard
Published: January 2018

Submarine mud volcanoes develop through the extrusion of methane‐rich fluids and sediments onto the seafloor. The morphology of a mud volcano can record its extrusive history and processes of erosion and deformation affecting it. The study of offshore mud volcano dynamics is limited because only few have been mapped at resolutions that reveal their detailed surface structures. More importantly, rates and volumes of extruded sediment and methane are poorly constrained. The 100 m high twin cones of Venere mud volcano are situated at ∼1,600 m water depth within Squillace Canyon along the Ionian Calabrian margin, Mediterranean Sea. Seafloor bathymetry and backscatter data obtained by a ship‐based system and an autonomous underwater vehicle (AUV) allow mapping of mudflow deposits of the mud volcano and bedforms in the surrounding canyon. Repeated surveying by AUV document active mud movement at the western summit in between 2014 and 2016. Through sediment coring and tephrochronology, ages of buried mudflow deposits are determined based on the sedimentation rate and the thickness of overlying hemipelagic sediments. An average extrusion rate of 27,000 m3/yr over the last ∼882 years is estimated. These results support a three‐stage evolutionary model of Venere mud volcano since ∼4,000 years ago. It includes the onset of quiescence at the eastern cone (after ∼2,200 years ago), erosive events in Squillace Canyon (prior to ∼882 years ago), and mudflows from the eastern cone (since ∼882 years). This study reveals new interactions between a mud volcano and a canyon in the deep sea.
Late Quaternary Deep Stratification‐Climate Coupling in the Southern Ocean: Implications for Changes in Abyssal Carbon Storage
Authors: Wu Li , Wang Rujian , Xiao Wenshen , Krijgsman Wout , Li Qianyu , Ge Shulan , Ma Tong
Published: January 2018

The Southern Ocean plays an important role in modulating Pleistocene atmospheric CO2 concentrations, but the underlying mechanisms are not yet fully understood. Here, we report the laser grain‐size distribution and Mn geochemical data of a 523 kyr‐long sediment record (core ANT30/P1‐02 off Prydz Bay; East Antarctica) to trace past physical changes in the deep Southern Ocean. The core sediments are predominantly composed of clay and silt‐sized material. Three grain size end‐members (EM) as well as three sensitive grain size classes (SC) were discerned, interpreted as Ice Rafted Debris (EM1 and SC1), and coarse (EM2 and SC2) and fine (EM3, SC3) materials deposited from bottom nepheloid layers, respectively. Ratios of EM2/(EM2 + EM3) and SC2/SC3 reveal changes in the local bottom current strength, which is related to the deep ocean diapycnal mixing rate, showing higher values during interglacial periods and lower values during glacial periods. MnO was enriched at each glacial termination, probably caused by abrupt elevations in Antarctic bottom water (AABW) formation rate. Lower AABW formation rate and reduced deep diapycnal mixing during glacial periods enhanced deep Southern Ocean stratification, contributing to glacial atmospheric CO2 drawdown. The elevated AABW formation and enhanced deep diapycnal mixing during glacial terminations alleviated such deep stratification, promoting deeply sequestered CO2 to outgas.
Widespread Moulin Formation During Supraglacial Lake Drainages in Greenland
Authors: Hoffman Matthew J. , Perego Mauro , Andrews Lauren C. , Price Stephen F. , Neumann Thomas A. , Johnson Jesse V. , Catania Ginny , Lüthi Martin P.
Published: January 2018

Moulins permit access of surface meltwater to the glacier bed, causing basal lubrication and ice speedup in the ablation zone of western Greenland during summer. Despite the substantial impact of moulins on ice dynamics, the conditions under which they form are poorly understood. We assimilate a time series of ice surface velocity from a network of eleven Global Positioning System receivers into an ice sheet model to estimate ice sheet stresses during winter, spring, and summer in a ∼30 × 10 km region. Surface‐parallel von Mises stress increases slightly during spring speedup and early summer, sufficient to allow formation of 16% of moulins mapped in the study area. In contrast, 63% of moulins experience stresses over the tensile strength of ice during a short (hours) supraglacial lake drainage event. Lake drainages appear to control moulin density, which is itself a control on subglacial drainage efficiency and summer ice velocities.
Assimilation of Himawari‐8 All‐Sky Radiances Every 10 Minutes: Impact on Precipitation and Flood Risk Prediction
Authors: Honda T. , Kotsuki S. , Lien G.‐Y. , Maejima Y. , Okamoto K. , Miyoshi T.
Published: January 2018

Japan's new geostationary satellite “Himawari‐8” enables updating precipitation and flood predictions as frequently as every 10 min and to capture as early as possible the flood risk associated with rapidly changing severe weather. This study focuses on the advantage of the frequent update of precipitation and flood predictions by assimilating all‐sky Himawari‐8 infrared radiances in the case of September 2015 Kanto‐Tohoku heavy rainfall, a major flooding event in Japan. The analyzed tropical cyclone representation and moisture transport are improved by the Himawari‐8 data assimilation. Deterministic runs from the analyses with the Himawari‐8 data provide much improved forecasts of a strong precipitation band. Moreover, every 10 min updates of river discharge forecasts driven by these improved precipitation forecasts show a large improvement in forecast skill with longer lead times. The results demonstrate that the frequent refresh aids to capture a signature of flooding at an earlier stage.
Rapid Prototyping of Ultralow‐Cost, Inkjet‐Printed Carbon Microelectrodes for Flexible Bioelectronic Devices
Authors: Schnitker Jan , Adly Nouran , Seyock Silke , Bachmann Bernd , Yakushenko Alexey , Wolfrum Bernhard , Offenhäusser Andreas
Published: January 2018

Gaining better understanding of the human brain using chip‐based devices and promoting the recovery of lost biological functionality through implants are long pursued endeavors driven by advances in material science, bioelectronics, and the advancing silicon technology. While conventional bioelectronic and neuroelectronic devices typically rely on cleanroom‐based processing, a rapid prototyping technique is proposed that is based on high‐resolution inkjet printing featuring nanoporous carbon electrodes that yield excellent cell–chip coupling. This study aims to overcome two major limitations of conventional approaches that make the development of neuroelectronic devices very challenging and limit a wider use within the research community as well as industry: high costs and lack of rapid prototyping capabilities. These challenges are addressed with an all‐printed, high‐resolution approach that makes use of flexible polymer substrates and is fabricated on a fully digital printing platform. The manufacturing of a chip consumes less than 60 min and costs a few cents per chip. This study introduces nanoporous carbon as a cell‐interfacing electrode material that features outstanding properties for extracellular recording of action potentials and stimulation indicating that the printed carbon chips have the means to be used as a versatile neuroelectronic tool for in vitro and in vivo studies.
A Highly Stretchable Cross‐Linked Polyacrylamide Hydrogel as an Effective Binder for Silicon and Sulfur Electrodes toward Durable Lithium‐Ion Storage
Authors: Zhu Xingyu , Zhang Fei , Zhang Li , Zhang Liya , Song Yingze , Jiang Tao , Sayed Shah , Lu Chen , Wang Xiangguo , Sun Jingyu , Liu Zhongfan
Published: January 2018

Despite the recent advancement in the in‐practical active materials (e.g., silicon, sulfur) in the rechargeable lithium‐ion energy storage systems, daunting challenges still remain for these high‐capacity electrode material candidates to overcome the severe volume changes associated with the repeated lithiation/delithiation process. Herein, developing a room‐temperature covalently cross‐linked polyacrylamide (c‐PAM) binder with high stretchability and abundant polar groups targeting the construction of high‐performance Si and sulfur electrodes is focused on. The robust 3D c‐PAM binder network enables not only significant enhancement of the strain resistance for working electrodes but also strong affinity to bonding with nano‐Si surface as well as effective capture of the soluble Li2Sn intermediates, thereby giving rise to remarkably improved cycling performances in both types of electrodes. This rational design of such an effective and multifunctional binder offers a pathway toward advanced energy storage implementations.
Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect
Authors: Gao Fei , Xu Ziyang , Liang Qingfei , Liu Bo , Li Haofei , Wu Yuanhao , Zhang Yinyu , Lin Zifeng , Wu Mingming , Ruan Changshun , Liu Wenguang
Published: January 2018

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ⇔ sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.
Influence of incorporation methods of ATH on microstructure, elastomeric properties, flammability, and thermal decomposition of dynamically vulcanized NR/PP blends
Authors: Lopattananon Natinee , Walong Alif , Sakai Tadamoto
Published: January 2018

Flame‐retardant thermoplastic vulcanizates (TPVs) of natural rubber (NR)/polypropylene (PP) (60/40 wt %) blends filled with alumina trihydrate (ATH) were prepared with an internal mixer. To increase the properties of flame‐retardant NR/PP TPV, the new mixing method, stepwise masterbatch mixing (SMB) method was adopted. The effects of SMB method along with different ATH loadings on microstructure and properties of NR/PP TPVs were investigated. Conventional one‐step mixing (CV) method was also studied for comparison. Transmission electron microscopy analysis showed that different processes led to a variation in microstructural homogeneity, which imposed various effects on blend properties. The mechanical properties of TPVs changed with ATH loading, and the strength of the samples obtained from SMB method was higher than those of CV method. LOI and cone calorimetry tests revealed that the flame retardancy of NR/PP blends dramatically increased at higher ATH loading. Furthermore, the increment level of flame retardancy was accelerated in the blends produced particularly through SMB method, resulting from homogeneity of local ATH distribution in NR/PP blend. Greater combustion resistance of blends prepared from SMB route were confirmed by thermogravimetry and pyrolysis‐gas chromatography–mass spectrometry techniques. Finally, a burning mechanism between filler structure and flammability of NR/PP TPVs obtained from CV and SMB methods was discussed. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46231.
Patient-derived organoid models help define personalized management of gastrointestinal cancer
Authors: Aberle M R , Burkhart R A , Tiriac H , Olde Damink S W M , Dejong C H C , Tuveson D A , van Dam R M
Published: January 2018

Background

The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional ‘organoid’ models.

Methods

A PubMed search was conducted to identify relevant articles. An overview of the literature and published protocols is presented, and the implications of these models for patients with cancer, surgeons and oncologists are explained.

Results

Organoid culture methods have been established for healthy and diseased tissues from oesophagus, stomach, intestine, pancreas, bile duct and liver. Because organoids can be generated with high efficiency and speed from fine-needle aspirations, biopsies or resection specimens, they can serve as a personal cancer model. Personalized treatment could become a more standard practice by using these cell cultures for extensive molecular diagnosis and drug screening. Drug sensitivity assays can give a clinically actionable sensitivity profile of a patient's tumour. However, the predictive capability of organoid drug screening has not been evaluated in prospective clinical trials.

Conclusion

High-throughput drug screening on organoids, combined with next-generation sequencing, proteomic analysis and other state-of-the-art molecular diagnostic methods, can shape cancer treatment to become more effective with fewer side-effects.
Brain resting‐state networks in adolescents with high‐functioning autism: Analysis of spatial connectivity and temporal neurodynamics
Authors: Bernas Antoine , Barendse Evelien M. , Aldenkamp Albert P. , Backes Walter H. , Hofman Paul A. M. , Hendriks Marc P. H. , Kessels Roy P. C. , Willems Frans M. J. , de With Peter H. N. , Zinger Svitlana , Jansen Jacobus F. A.
Published: January 2018

Introduction

Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting‐state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high‐functioning young population. The aim of this study is to test whether high‐functioning adolescents with ASD (HFA) have an abnormal resting‐state functional connectivity.

Materials and Methods

We performed spatial and temporal analyses on resting‐state networks (RSNs) in 13 HFA adolescents and 13 IQ‐ and age‐matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics.

Results

Controls and HFA display very similar patterns and strengths of resting‐state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting‐state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices.

Conclusion

The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience‐executive network: a pathway involving cognitive, executive, and emotion‐related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.
The impact of a dose of the angiotensin receptor blocker valsartan on post‐myocardial infarction ventricular remodelling
Authors: Park Kyungil , Kim Young‐Dae , Kim Ki‐Sik , Lee Su‐Hoon , Park Tae‐Ho , Lee Sang‐Gon , Kim Byung‐Soo , Hur Seung‐Ho , Yang Tae‐Hyun , Oh Joo‐Hyun , Hong Taek‐Jong , Park Jong‐Sun , Hwang Jin‐Yong , Jeong Byungcheon , Bae Woo‐Hyung ,   VALID Investigators
Published: January 2018

Aims

Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk–benefit profile of different doses have not been fully identified.

Methods and results

In this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (<50%) were randomly allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to 320 mg/day, n = 333) or low‐dose valsartan (80 mg/day, n = 162) treatment. The primary objective was to assess the changes in echocardiographic parameters of LV remodelling from baseline to 12 months after discharge. After treatment, end‐diastolic LV volume (LVEDV) decreased significantly in the low‐dose group, but the difference in LVEDV changes was insignificant between the maximal‐tolerated‐dose and low‐dose groups. End‐systolic LV volume decreased significantly in both groups, to a similar degree between groups. LV ejection fraction rose significantly in both study groups, to a similar degree. Changes in plasma levels of neurohormones were also comparable between the two groups. Drug‐related adverse effects occurred more frequently in the maximal‐tolerated‐dose group than in the low‐dose group (7.96 vs. 0.69%, P < 0.001).

Conclusions

In the present study, treatment with the maximal tolerated dose of valsartan did not exhibit a superior effect on post‐MI LV remodelling compared with low‐dose treatment and was associated with a greater frequency of adverse effect in Korean patients. Further study with a sufficient number of cases and statistical power is warranted to verify the findings of the present study.
Optimization of Novel Oil Extraction Technique From Canola Seeds: Lecithin‐Based Microemulsion
Authors: Radi Mohsen , Abbasi Soleiman
Published: January 2018

Nowadays, solvent (hexane) based oil extraction is a widely used commercial technique and there are a number of environmental, economic, and health related concerns. Overcoming such serious issues is driving research to develop alternative safe methods. In the present study, a novel technique, using lecithin‐based microemulsion system, is developed for canola oil extraction. At first, pseudoternary phase diagrams of canola oil/lecithin/propanol/water microemulsions are constructed and the effect of temperature on microemulsion formation was evaluated. So that, (lecithin/propanol)/water microemulsion premixes ([2:1]50:50 and [2:3]80:20) are selected for optimization (temperature, exposure time, premix:canola seeds ratio, and agitation rate) of oil extraction from canola seeds using one factor at a time design. Based on “one factor at a time” design, the highest extraction yield (82.6% wt) achieved at 60 °C, 60 min, 6:1 premix:canola seeds ratio without agitation; the premix composition was (lecithin/propanol)/water (2:1)50:50. From quality point of views, the microemulsion‐based extracted oils has lower peroxide value, higher acidity, as well as low phosphorous and lecithin contents in comparison with hexane extracted one. This technique confirms its simultaneous extraction, recovery, and solubilization capabilities which can be used for oil extraction and food formulation.

Practical Applications: For many decades, vegetable oils are commonly extracted by mechanical pressing or extraction with solvents such as hexane. Hexane, a highly volatile and flammable solvent which requires expensive equipment for safe operation, is classified as a hazardous air pollutant and occupational exposure to n‐hexane can cause neurological symptoms and other health defects. Overcoming these serious issues is driving research to develop alternative safe methods such as microemulsion technique. This study introduces a novel technique using lecithin‐based microemulsion systems for extraction of edible oils from oilseeds. This technique, as a low energy consuming method, has great potency for being used as a safe and green oil extraction technique which is the developing direction for not only the dominant oil resources but also nutrient lipids which can be easily dissolvable in aqueous food and pharmaceutical formulations.

Accurate ratios of canola seeds, lecithin, 1‐propanol and water at a moderate temperature were used to create a nano‐size canola oil lecithin‐based microemulsion which was then simply demulsified at lower temperature in order to separate the extracted oil (see picture). This technique as a low energy consuming, straightforward and environmentally friendly method could be used for solublization and extraction of oil from various sources.
Thermal, Mechanical, and Morphological Properties of Rigid Crude Glycerol‐Based Polyurethane Foams Reinforced With Nanoclay and Microcrystalline Cellulose
Authors: Qi Xiaoge , Zhang Yongsheng , Chang Chun , Luo Xiaolan , Li Yebo
Published: January 2018

The enhancement of mechanical and thermal properties of rigid polyurethane foam (RPUF) achieved through a cost‐effective and sustainable approach remains an ongoing interest in both industry and academia. In this study, water‐blown rigid polyurethane (PU) foams based on crude glycerol (CG) polyol are developed and halloysite nanotubes (HN) and microcrystalline cellulose (MC) with different loadings of 1.0, 3.0, and 5.0% are incorporated to improve the performance of the foams, respectively. Effects of different loadings of HN or MC on the viscosity of CG polyols and the foaming process are investigated. CG‐based polyurethane (CGPU) foams and their foam composites (CG‐HN PU foams and CG‐MC PU foams) are characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The results reveal that HN is easier to disperse uniformly in the CG polyol than MC and CGPU foams with 1.0% of HN and MC shows significantly improved performance. Their compressive strength increases by 3.8 and 12.5%, respectively, as the HN and MC loadings increases from 0 to 1.0%. The thermal conductivities of CG PU foams reinforced with 1.0% of HN and MC are 37.79 and 37.94 mWm−1K−1, which are lower than that (38.24 mWm−1K−1) of CGPU foams without the addition of fillers. Moreover, compared to CGPU foams, both CG‐HN PU foams and CG‐MC PU foams show improved thermal stabilities, and the latter is higher than the former.

Practical Applications: Different fillers (HN and MC) are used to reinforce the CG‐based polyurethane, and water‐blown rigid PU biofoam composites with improved properties are prepared. The use of fillers (HN and MC) has the potential for the production of advanced CG‐based rigid PU foams.

Water‐blown rigid crude glycerol‐based polyurethane foams (PU) reinforced with halloysite nanotubes (HN) and microcrystalline cellulose (MC). The results reveal that HN is easier to disperse uniformly in the CG polyol than MC and CGPU foams with 1.0% of HN and MC show significantly improved performance. The thermal conductivities of CG PU foams reinforced with 1.0% of HN and MC are 37.79 and 37.94 mWm−1K−1, which are lower than that of CGPU foams without the addition of fillers. Moreover, compared to CGPU foams, both CG‐HN PU foams and CG‐MC PU foams show improved thermal stabilities.
Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity
Authors: de Pierrefeu Amicie , Fovet Thomas , Hadj‐Selem Fouad , Löfstedt Tommy , Ciuciu Philippe , Lefebvre Stephanie , Thomas Pierre , Lopes Renaud , Jardri Renaud , Duchesnay Edouard
Published: January 2018

Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time‐consuming. This article first proposes a machine‐learning algorithm to automatically identify resting‐state fMRI periods that precede hallucinations versus periods that do not. When applied to whole‐brain fMRI data, state‐of‐the‐art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty. Based on this approach, we obtained reliable classifying performances associated with interpretable predictive patterns, composed of two clearly identifiable clusters in speech‐related brain regions. The variation in transition‐to‐hallucination functional patterns not only from one patient to another but also from one occurrence to the next (e.g., also depending on the sensory modalities involved) appeared to be the major difficulty when developing effective classifiers. Consequently, second, this article aimed to characterize the variability within the prehallucination patterns using an extension of principal component analysis with spatial constraints. The principal components (PCs) and the associated basis patterns shed light on the intrinsic structures of the variability present in the dataset. Such results are promising in the scope of innovative fMRI‐guided therapy for drug‐resistant hallucinations, such as fMRI‐based neurofeedback.
At the core of reasoning: Dissociating deductive and non‐deductive load
Authors: Coetzee John P. , Monti Martin M.
Published: January 2018

In recent years, neuroimaging methods have been used to investigate how the human mind carries out deductive reasoning. According to some, the neural substrate of language is integral to deductive reasoning. According to others, deductive reasoning is supported by a language‐independent distributed network including left frontopolar and frontomedial cortices. However, it has been suggested that activity in these frontal regions might instead reflect non‐deductive factors such as working memory load and general cognitive difficulty. To address this issue, 20 healthy volunteers participated in an fMRI experiment in which they evaluated matched simple and complex deductive and non‐deductive arguments in a 2 × 2 design. The contrast of complex versus simple deductive trials resulted in a pattern of activation closely matching previous work, including frontopolar and frontomedial “core” areas of deduction as well as other “cognitive support” areas in frontoparietal cortices. Conversely, the contrast of complex and simple non‐deductive trials resulted in a pattern of activation that does not include any of the aforementioned “core” areas. Direct comparison of the load effect across deductive and non‐deductive trials further supports the view that activity in the regions previously interpreted as “core” to deductive reasoning cannot merely reflect non‐deductive load, but instead might reflect processes specific to the deductive calculus. Finally, consistent with previous reports, the classical language areas in left inferior frontal gyrus and posterior temporal cortex do not appear to participate in deductive inference beyond their role in encoding stimuli presented in linguistic format.
Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient‐derived primary and metastatic lung cancer cells
Authors: Sette Giovanni , Salvati Valentina , Giordani Ilenia , Pilozzi Emanuela , Quacquarini Denise , Duranti Enrico , De Nicola Francesca , Pallocca Matteo , Fanciulli Maurizio , Falchi Mario , Pallini Roberto , De Maria Ruggero , Eramo Adriana
Published: January 2018

Availability of tumor and non‐tumor patient‐derived models would promote the development of more effective therapeutics for non‐small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient‐derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non‐tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non‐malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor‐specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies‐derived cultures rapidly lost patient‐specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient‐derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non‐malignant lung epithelial stem cells from either tumor or non‐tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor‐derived CRC cultures are composed of (non‐tumoral) airway basal cells.
Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8
Authors: Chen Yinan , Zhao Fengbo , Cui Daming , Jiang Rui , Chen Jian , Huang Qingfeng , Shi Jinlong
Published: January 2018

Glioma development is an extremely complex process with changes occurring in numerous genes. HOXD antisense growth‐associated long noncoding RNA (HOXD‐AS1), an important long noncoding RNA (lncRNA), is known to regulate metastasis‐related gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we elucidated the function and possible molecular mechanisms of lncRNA HOXD‐AS1 in human glioma cells. Our results proved that HOXD‐AS1 expression was upregulated in glioma tissues and in glioma cell lines. HOXD‐AS1 overexpression promoted cell migration and invasion in vitro, whereas knockdown of HOXD‐AS1 expression repressed these cellular processes. Mechanistic studies further revealed that HOXD‐AS1 could compete with the transcription factor E2F8 to bind with miR‐130a, thus affecting E2F8 expression. Additionally, reciprocal repression was observed between HOXD‐AS1 and miR‐130a, and miR‐130a mediated the tumor‐suppressive effects of HOXD‐AS1 knockdown. Taken together, these results provide a comprehensive analysis of the role of HOXD‐AS1 in glioma cells and offer important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human glioma.
Different effects of dexmedetomidine and midazolam on the expression of NR2B and GABAA‐α1 following peripheral nerve injury in rats
Authors: Chen Jiayu , Li Hanjun , Lim Grewo , McCabe Michael F. , Zhao Wei , Yang Yunli , Ma Weiqing , Li Na
Published: January 2018

Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model. Intramuscular injection with DEX and MZL attenuated the development of mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury (CCI). Concurrently, the expression of NMDA receptor subunit 2B (NR2B), GABA (A) receptor subunit alpha1 (GABAA‐α1), and Sonic Hedgehog (SHH) displayed different temporal patterns in the thalamus and the ipsilateral dorsal horn of the spinal cord after CCI. Such that (1) NR2B expression was decreased on day 1 and 14, whereas GABAA‐α1 expression was increased on day 1 in the thalamus, and NR2B expression was decreased on day 1, whereas GABAA‐α1 expression was increased on day 1 and day 30 in the ipsilateral spinal cord dorsal horn after DEX treatment. (2) NR2B expression was increased on day 1, then decreased on day 14 and returned to baseline on day30, whereas GABAA‐α1 expression was no significant changes on day 1, 14, 30 in the thalamus, and NR2B expression was decreased on day 14 and 30, whereas GABAA‐α1 expression was no changes on day 1 and 14 but increased on day 30 after MZL treatment. Furthermore, the mechanical allodynia was significantly attenuated after PUR administration. Meanwhile the expression of NR2B was significantly decreased, and the expression of GABAA‐α1 was significantly increased, in the thalamus and in the ipsilateral spinal cord dorsal horn when detected on postoperative day 1, 7, and 14. Our findings indicate that DEX and MZL have different mechanisms in CCI rats, suggesting different strategies could be considered in managing neuropathic pain in different individuals. © 2018 IUBMB Life, 70(2):143–152, 2018
The Role of Kupffer Cells After Major Liver Surgery
Authors: Prins Hubert A. , Meijer Catharina , Boelens Petra G. , Nijveldt Robert J. , Siroen Michiel P. C. , Masson Sylvie , Daveau Maryvonne , Scotté Michel , Diks Jeroen , van Leeuwen Paul A. M.
Published: January 2018

Background: Kupffer cells (KCs) are the resident macrophages of the liver. KCs have an enormous endotoxin eliminating capacity. Endotoxins play an important role in the development of systemic complications after partial hepatectomy by activating KCs. The role of KCs and endotoxins after partial hepatectomy is investigated. Methods: Wistar rats (n = 16, 250–275 g) were randomly assigned to have 1 mL dichloromethylene‐diphosphonate (CL2MDP) or 1 mL NaCl 0.9% IV. Forty‐eight hours later, all rats received a two‐thirds liver resection. Twenty‐four hours later, rats received at random 50 μg/kg endotoxin (LPS) in 1 mL or 1 mL of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion. Results: CL2MDP infusion resulted in a complete KC elimination. KC‐depleted rats had the lowest mean arterial pressure, the highest heart and ventilatory rate after endotoxemia. All rats were able to maintain pH in normal ranges. The KC‐depleted rats after partial hepatectomy had the lowest CO2 levels and the highest levels of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic, pulmonary, and renal mRNA expression of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β were decreased in KC‐depleted rats. Plasma levels of TNF‐α were significantly decreased in KC‐depleted rats. Furthermore, the highest influx of macrophages and polymorphonuclear cells in the lung and kidney were measured in KC‐depleted rats during endotoxemia. Conclusions: Partial hepatectomy in KC‐depleted rats result in a more pronounced endotoxin‐mediated systemic inflammation and decreased synthesis of cytokines.
Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation
Authors: Guntur Anyonya R , Gerencser Akos A , Le Phuong T , DeMambro Victoria E , Bornstein Sheila A , Mookerjee Shona A , Maridas David E , Clemmons David E , Brand Martin D , Rosen Clifford J
Published: January 2018

Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research.