bluuebunny/crossref_metadata_2025 huggingface dataset:
Alginate as a support ligand for enhanced colloidal liquid aphron immobilization of proteins and drug delivery
Authors: Ward Keeran , Cortés Juan Guillermo Cediel , Stuckey David
Published: August 2019

Research within the field of colloidal liquid aphrons (CLAs) for enzyme immobilization has often used ionic surfactants for the retention of enzymes. Although these charged interactions allow for enhanced immobilization, they can often lead to denaturation of enzyme activity, and even release of the protein. Sodium alginate has been used in drug delivery applications due to its low toxicity and charged interactions that allow for encapsulation. Hence, alginate systems can be used as an alternative to ionic surfactants in CLA immobilization. This paper presents, for the first time, the use of sodium alginate as potential ligand for enhanced CLA immobilization. The use of five model proteins; lysozyme, bovine serum albumin, ovalbumin, insulin, and α‐chymotrypsin, of various pIs and hydrophobicities, showed the relevance of electrostatic interactions in promoting binding with sodium alginate when the pH < pI, with 100% immobilization attributed to alginate incorporated CLAs over general nonionic formulations. Furthermore, above their pI, >80% protein recovery was observed, with activity and conformation comparable to their native counterparts. Finally, the use of proteolysis showed that as the degree of ionic bonding increased between the protein and sodium alginate, the degree of protease resistance decreased due to conformational changes experienced during binding.
Efficient biosynthesis of antitumor ganoderic acid HLDOA using a dual tunable system for optimizing the expression of CYP5150L8 and a Ganoderma P450 reductase
Authors: Lan Xiaoting , Yuan Wei , Wang Meng , Xiao Han
Published: August 2019

Ganoderic acid 3‐hydroxy‐lanosta‐8,24‐dien‐26‐oic acid (GA‐HLDOA), an antitumor triterpenoid from the traditional Chinese medicinal higher fungus Ganoderma lucidum, is considered as a key precursor for biosynthesizing other ganoderic acids (GAs) with superior antitumor activities. Our previous study identified CYP5150L8 from G. lucidum as a lanosterol oxidase, and achieved heterologous biosynthesis of GA‐HLDOA in Saccharomyces cerevisiae. However, low production of GA‐HLDOA in either G. lucidum or heterologous host hindered its further investigation and application. In this study, we constructed a dual tunable system for balancing the expression of CYP5150L8 and a Ganoderma P450 reductase iGLCPR, and performed a comprehensive optimization of CYP5150L8 expression, iGLCPR expression, and glycerol usage. Then, we investigated the fermentation behavior of the best strain in optimized condition in flask and achieved 154.45 mg/L GA‐HLDOA production, which was 10.7‐fold higher compared with previous report. This study may facilitate the wide‐spread application of GA‐HLDOA and the discovery of unknown cytochrome P450s in downstream GAs biosynthesis.
Comprehensive comparison of the anti‐inflammatory activity and chemical consistency of traditional Chinese medicine formula granules with Ge‐Gen decoction as a representative sample
Authors: Qin You , Zhou Rongrong , Huang Jianhua , Jin Jian , Zhou Qingyijun , Liu Hao , Xiao Juan , Zhao Yahui , Shu Jun , Zhang Shuihan , Huang Luqi
Published: August 2019

Traditional Chinese medicine formula granules (TCMFGs), an advanced dosage form of traditional Chinese medicine, are entering the market on a large scale. However, little attention has been paid to the simultaneous efficacy assessment and quality control of this advanced dosage form. In this study, a comprehensive comparison of the pharmacological activity and chemical consistency of TCMFGs from different manufacturers was performed. Ge‐Gen decoction (GGD) samples were used as the target TCMFG. The in vitro anti‐inflammatory effects among different types of GGDs indicate that all of them showed different abilities to reduce the lipopolysaccharide‐activated production of nitric oxide, interleukin‐1β (IL‐1β), IL‐6 and tumor necrosis factor‐α. The results from a dimethylbenzene‐induced inflammation model in mice indicated that the nine samples in this study showed significant in vivo anti‐inflammatory effects. Qualitative and quantitative analyses were performed by multiwavelength ultra‐high‐performance liquid chromatography with diode array detection and electrospray ionization with quadrupole time‐of‐flight–tandem mass spectrometry. To visually interpret the differences in the chemical materials, a scatter plot analysis was performed. According to the scatter plot analysis, nine compounds were evaluated as important contributors to the differences. This is the first report of TCMFGs on the basis of the spectrum‐effect consistency.
Emotional stability is associated with the MAOA promoter uVNTR polymorphism in women
Authors: Rodríguez‐Ramos Ángel , Moriana Juan Antonio , García‐Torres Francisco , Ruiz‐Rubio Manuel
Published: August 2019

Background

Neuroticism is associated with low emotional stability, and it is characterized by a tendency to perceive ordinary situations as threatening and difficult to manage. This personality trait has been associated with psychological distress and predicts some mental disorders. Previous studies have shown that women tend to be more neurotic than men and, in general, females have also a higher incidence of anxious and depressive disorders.

Methods

We analyzed in a sample of 99 female university students (from 18 to 26 years old) if emotional stability, measured using the Big Five Questionnaire, was linked to polymorphic variants in candidate genes related to dopaminergic and serotonergic systems, and other personality variables.

Results

We found that emotional stability and its subdimensions are genetically associated with MAOA‐uVNTR polymorphism. Thus, women carriers of the 3‐repeat allele (lower MAO‐A expression) showed higher levels of emotional stability. No associations were found with other polymorphisms analyzed, including COMT Val158Met, 5‐HTTLPR, and DAT 3′UTR VNTR. Furthermore, our results showed a negative correlation between emotional stability and depression, state anxiety, and trait anxiety. In fact, MAOA‐uVNTR and trait anxiety also explained emotional stability and its subdimensions. We also found that other genetic characteristic, phenylthiocarbamide tasting, explained impulsivity, specifically tasters controlled impulses better than nontasters.

Conclusion

Our results indicate that neuroticism might be regulated by MAOA and could be a common factor between different phenotypes, such as aggressive behaviors or personality disorders, observed in women with higher activity genotype who had been exposed to negative environments during childhood. This study could lead to a better understanding of the basis of emotional stability and could lead to future projects for this purpose.
Microsurgical Anatomy of the Superior Wall of the Mandibular Canal and Surrounding Structures: Suggestion for New Classifications for Dental Implantology
Authors: Iwanaga Joe , Anand Mahindra Kumar , Jain Mitesh N. , Nagata Mizuki , Matsushita Yuki , Ibaragi Soichiro , Kusukawa Jingo , Tubbs R. Shane
Published: August 2019

Our goal was to clarify the relationship between the superior wall of the mandibular canal and the presence of teeth. We also sought to study the structural changes of the mandibular canal after tooth loss. Twenty sides from 10 dry mandibles derived from six males and four females were used for this study. The age of the specimens at the time of death ranged from 57 to 91 years. The mandibles were cut in the midline resulting in 20 hemi‐mandibles. The presence of teeth (from the second premolar to the third molar) was recorded for each hemi‐mandible. The mandibular canal in the body of the mandible was divided into four areas, that is, Areas 1–4. The superior wall of the mandibular canal and a cancellous bone pattern above the mandibular canal were observed. Next, the mandibular canal was horizontally cut at its center and the superior wall of the mandibular canal observed inferiorly. A total of 75 areas (20 dentulous areas and 55 edentulous areas) were produced. The distal view was classified into three groups, Type I (trabecular pattern), Type II (osteoporotic pattern), and Type III (dense/irregular pattern). The Type I pattern was found in 60.0% (12/20) of the dentulous areas and 32.7% of the edentulous areas. While the Type II pattern was found in 15.0% (23/55) of the dentulous areas and 41.8% of the edentulous areas. The inferior view was classified into four groups depending on the surface of the superior wall of the mandibular canal, that is, Class I (trabecular pattern), Class II (osteoporotic pattern), Class III (dense/irregular pattern), and Class IV (smooth).The Class I pattern was seen most frequently (55.0%) in dentulous areas and the Class IV pattern (45.5%) most frequently in edentulous areas. Based on these results, we conclude that the superior wall of the mandibular canal could change following tooth loss. Clin. Anat. 33:223–231, 2020. © 2019 Wiley Periodicals, Inc.
The “Valva Cerebri”: Morphometry, Topographic Anatomy and Histology of the Rhomboid Membrane at the Craniocervical Junction
Authors: Kurucz Peter , Meszaros Cintia , Ganslandt Oliver , Buchfelder Michael , Barany Laszlo
Published: August 2019

The arachnoid membranes' anatomy is a controversial topic in the literature, and the rhomboid membrane at the craniovertebral junction is an element of this system that has been described poorly. Hence, the objective of our study was to examine this membrane's anatomy and histology. A total of 45 fresh formalin‐fixed human cadaveric heads were examined, and anatomic dissections and histologic examinations using standard staining methods were performed. The membrane was found to be a constant structure. It has a rhomboid shape and is located on the medulla oblongata and upper cervical spine's ventral surface within the subarachnoid space. Its average craniocaudal length is 49 mm and the short axis is 26 mm. The cranial apex is attached to the vertebral arteries' junction, and the caudal apex reaches the level of C4. The lateral apices are attached to the dura mater at the level of the denticulate ligament's second insertion. The C1 spinal nerves perforate the membrane, while the C2 roots are located dorsal to it. The membrane is attached strongly to the underlying pia mater. Histologically, it has a typical arachnoid structure, in which its adhesions to the vertebral arteries as well as to the pia mater could be verified histologically. This is the first detailed examination of the rhomboid membrane. Our results suggest that the membrane serves a valve‐like function between the spinal and cranial subarachnoid spaces. Based on our findings, further hydrodynamic studies should clarify the membrane's physiological role. Clin. Anat. 32:56–65, 2019. © 2019 Wiley Periodicals, Inc.
Correlation between Sternal Slope Angle and Primary Spontaneous Pneumothorax in Young Males, a Propensity Score Match Analysis
Authors: Liu Yong , Cheng Jing , Xu Jiahang , Yu Junjie , Zhao Liang , Zhao Ke , Chen Baojun
Published: August 2019

It is generally accepted that primary spontaneous pneumothorax (PSP) is found mostly in tall, thin young males. However, the precise etiology of PSP is unclear. We compared some thoracic structural angles of PSPs and controls in young males to determine the predominant factor. CT data of 43 male PSPs (age 21.88 ± 5.30) and 30 controls (age 21.47 ± 5.47) were collected. The angle of thoracic vertebrae slope (∠α), sternal slope angle (∠β), and tracheal‐sternal stem angle (∠γ) were measured in the sagittal position. Carina angle (∠δ) was measured in the coronal position. After a propensity score match (PSM) of age and smoking history, the angles were comparatively evaluated. There were significant differences in all four angles between two unmatched groups, while only in three (∠β, ∠γ, and ∠δ) after PSM was performed. The correlation between ∠β and PSP was most significant, and R2 was 0.456. The prediction accuracy of ∠β was 81.3%, OR was 1.386, 95% confidence interval was (1.095–1.754). The sternal slope angles in PSPs are greater than controls indicate the sternal slope angle is associates with the development of PSP and it could be a thoracic structural index to predict the risk of PSP occurrence. Clin. Anat. 33:605–609, 2020. © 2019 Wiley Periodicals, Inc.
Phase II trial of ponatinib in patients with bevacizumab‐refractory glioblastoma
Authors: Lee Eudocia Q. , Muzikansky Alona , Duda Dan G. , Gaffey Sarah , Dietrich Jorg , Nayak Lakshmi , Chukwueke Ugonma N. , Beroukhim Rameen , Doherty Lisa , Laub Caroline Kane , LaFrankie Debra , Fontana Brittney , Stefanik Jennifer , Ruland Sandra , Caruso Victoria , Bruno Jennifer , Ligon Keith , Reardon David A. , Wen Patrick Y.
Published: August 2019

Background

Responses to bevacizumab in glioblastoma (GBM) are not durable. Plasma levels of basic fibroblast growth factor (bFGF) increase at the time of tumor progression. By targeting vascular endothelial growth factor receptor (VEGFR), platelet‐derived growth factor receptor, Src, and FGF receptor pathways, ponatinib may potentially help to overcome some of the putative mechanisms of adaptive resistance.

Methods

We performed a phase II trial of ponatinib in patients with bevacizumab‐refractory GBM and variants. Adult patients with Karnofsky performance score (KPS) ≥60, measurable disease, and normal organ and marrow function received 45 mg ponatinib daily. No limit on the number of prior therapies but only one prior bevacizumab‐containing regimen was allowed. Primary endpoint was 3‐month progression‐free survival. Plasma biomarkers of angiogenesis and inflammation were evaluated before and after treatment.

Results

The study closed after the first stage. Fifteen patients enrolled: median age 61 [27‐74]; median KPS 80 [70‐90]; median number of prior relapses 2 [2‐4]. Three‐month progression‐free survival rate was 0, median overall survival was 98 days [95% CI 56, 257], and median PFS was 28 days [95% CI 27, 30]. No responses were seen. The most common grade ≥3 adverse events included fatigue (n = 3), hypertension (2), and lipase elevation (2). Ponatinib treatment significantly increased plasma VEGF, soluble (s)VEGFR1, sVEGFR2, sTIE2, interferon gamma (IFNγ), tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐10 and decreased sVEGFR2.

Conclusions

Ponatinib was associated with minimal activity in bevacizumab‐refractory GBM patients. Circulating biomarker data confirmed pharmacodynamic changes and suggested that resistance to ponatinib may be related to an increase in inflammatory cytokines.
Ubiquitin C‐Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine‐Based Inhibitor
Authors: Krabill Aaron D. , Chen Hao , Hussain Sajjad , Feng Chao , Abdullah Ammara , Das Chittaranjan , Aryal Uma K. , Post Carol Beth , Wendt Michael K. , Galardy Paul J. , Flaherty Daniel P.
Published: August 2019

The deubiquitinase (DUB) ubiquitin C‐terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small‐molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine‐based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.
Late‐term safety and effectiveness of everolimus‐eluting stents in chronic total coronary occlusion revascularization: Final 4‐year results from the evaluation of the XIENCE coronary stent, Performance, and Technique in Chronic Total Occlusions (EXPERT CTO) multicenter trial
Authors: Kandzari David E. , Karmpaliotis Dimitri , Kini Annapoorna S. , Moses Jeffrey W. , Tummala Pradyumna E. , Grantham J. Aaron , Orr Charles , Lombardi William , Nicholson William J. , Lembo Nicholas J. , Popma Jeffrey J. , Wang Jin , Zhao Weiying , McGreevy Robert
Published: August 2019

Background

Limited study has detailed the late‐term safety and efficacy of chronic total coronary occlusion (CTO) revascularization among multiple centers applying modern techniques and with newer‐generation drug‐eluting stents.

Methods

Among 20 centers, 222 patients enrolled in the XIENCE coronary stent, performance, and technique (EXPERT) CTO trial underwent CTO percutaneous coronary intervention (PCI) with everolimus‐eluting stents (EES). Through planned 4‐year follow‐up, the primary composite endpoint of major adverse cardiac events (MACE; death, myocardial infarction [MI] and target lesion revascularization) and rates of individual component endpoints and stent thrombosis were determined.

Results

Demographic, lesion, and procedural characteristics included prior bypass surgery, 9.9%; diabetes, 40.1%; lesion length, 36.1 ± 18.5 mm; and stent length, 51.7 ± 27.2 mm. By 4 years, MACE rates were 31.6 and 22.4% by the pre‐specified ARC and per‐protocol definitions, respectively. Clinically‐indicated target lesion revascularization at 4 years was 11.3%. In landmark analyses of events beyond the first year of revascularization, the annualized rates of target vessel‐related MI and clinically‐indicated target lesion revascularization were 0.53 and 1.3%, respectively. Through 4 years, the cumulative definite/probable stent thrombosis rate was 1.7% with no events occurring beyond the initial year of index revascularization.

Conclusions

In a multicenter registration trial representing contemporary technique and EES, these results demonstrate sustained long‐term safety and effectiveness of EES in CTO percutaneous revascularization and can be used to inform shared decision making with patients being considered for CTO PCI relative to late safety and vessel patency.
Impact of Cellulose and Surfactants on Mass Transfer of Bubble Columns
Authors: Ahmia Aida C. , Idouhar Madjid , Wongwailikit Kritchart , Dietrich Nicolas , Hébrard Gilles
Published: August 2019

The effects of cellulose, surfactants, and their combination on the hydrodynamic behavior and the liquid‐side mass transfer coefficient of a bubble column were evaluated. For that purpose, different aqueous solutions containing surfactants (sodium dodecyl sulfate) and cellulose (microcrystalline cellulose, MCC) were investigated. The interfacial areas were calculated from the bubble diameters, the bubble frequencies, and the terminal bubble rising velocities. The liquid‐side mass transfer coefficients were determined from the volumetric mass transfer coefficients measured by the dynamic method. In the concentration range under test, the experimental results proved that the addition of MCC to the studied liquid phases did not affect the mass transfer coefficient.
Molecular Dynamics Simulation of Methane Hydrate Decomposition in the Presence of Alcohol Additives
Authors: Sun Xiaoliang , Zhou Guanggang , Zhu Jianwei , Wu Haicheng , Lu Guiwu , Bai Dongsheng
Published: August 2019

The decomposition process of methane hydrate in pure water and methanol aqueous solution was studied by molecular dynamics simulation. The effects of temperature and pressure on hydrate structure and decomposition rate are discussed. The results show that decreasing pressure and increasing temperature can significantly enhance the decomposition rate of hydrate. After adding a small amount of methanol molecules, bubbles with a diameter of about 2 nm are formed, and the methanol molecules are mainly distributed at the gas‐liquid interface, which greatly accelerates the decomposition rate and gas‐liquid separation efficiency. The radial distribution function and sequence parameter analysis show that the water molecules of the undecomposed hydrate with ordered ice‐like configuration at a temperature of 275 K evolve gradually into a long‐range disordered liquid structure in the dynamic relaxation process. It was found that at temperatures above 280 K and pressures between 10 atm and 100 atm, the pressure has no significant effect on hydrate decomposition rate, but when the pressure is reduced to 1 atm, the decomposition rate increases sharply. These findings provided a theoretical insight for the industrial exploitation of hydrates.
Chronic radiation exposure at Chernobyl shows no effect on genetic diversity in the freshwater crustacean, Asellus aquaticus thirty years on
Authors: Fuller Neil , Ford Alex T. , Lerebours Adélaïde , Gudkov Dmitri I. , Nagorskaya Liubov L. , Smith Jim T.
Published: August 2019

Analysis of genetic diversity represents a fundamental component of ecological risk assessments in contaminated environments. Many studies have assessed the genetic implications of chronic radiation exposure at Chernobyl, generally recording an elevated genetic diversity and mutation rate in rodents, plants, and birds inhabiting contaminated areas. Only limited studies have considered genetic diversity in aquatic biota at Chernobyl, despite the large number of freshwater systems where elevated dose rates will persist for many years. Consequently, the present study aimed to assess the effects of chronic radiation exposure on genetic diversity in the freshwater crustacean, Asellus aquaticus, using a genome‐wide SNP approach (Genotyping‐by‐sequencing). It was hypothesized that genetic diversity in A. aquaticus would be positively correlated with dose rate. A. aquaticus was collected from six lakes in Belarus and the Ukraine ranging in dose rate from 0.064 to 27.1 µGy/hr. Genotyping‐by‐sequencing analysis was performed on 74 individuals. A significant relationship between geographical distance and genetic differentiation confirmed the Isolation‐by‐Distance model. Conversely, no significant relationship between dose rate and genetic differentiation suggested no effect of the contamination gradient on genetic differentiation between populations. No significant relationship between five measures of genetic diversity and dose rate was recorded, suggesting that radiation exposure has not significantly influenced genetic diversity in A. aquaticus at Chernobyl. This is the first study to adopt a genome‐wide SNP approach to assess the impacts of environmental radiation exposure on biota. These findings are fundamental to understanding the long‐term success of aquatic populations in contaminated environments at Chernobyl and Fukushima.
Palladium(II), Rhodium(I), and Iridium(I) Complexes Containing O‐Functionalized 1,2,3‐Triazol‐5‐ylidene Ligands
Authors: Pretorius René , McDonald Ava , Regueira Beltrão da Costa Ligia , Müller‐Bunz Helge , Albrecht Martin
Published: August 2019

Strategies towards the synthesis of palladium(II), rhodium(I) and iridium(I) complexes bearing O‐functionalized triazolylidene ligands are reported. Mono‐ and dimetallic triazolylidene palladium complexes with ether, acetate, and hydroxy functionalities were synthesized using silver transmetalation. Selective formation of either the mono‐ or dimetallic palladium chlorido complexes was controlled by the amount of NMe4Cl used as an auxiliary in the metalation step, as excess halide traps the palladium precursor as unreactive palladate [PdCl4]2–. Analogous rhodium(I) and iridium(I) complexes with ether and acetate substituents were accessible by a silver transmetalation protocol, while alkoxide‐tethered triazolylidene complexes required base‐mediated metalation procedures. The alkoxide‐functionalized C,O‐bidentate chelating triazolylidene ligand is hemilabile and metalacycle opening and closing is triggered by the presence of acid and base, respectively. Such ligand versatility is attractive for bond activation catalysis.
The effects of graphic metaphor, gesture interaction, and form factor on e‐book performances and preferences
Authors: Park Kyeongjin , Seok Hyesung , Kim Kyungdoh
Published: August 2019

Reading e‐books on touch‐based mobile devices such as smartphones and tablet personal computer (PCs) are increasing. We conducted a comparative study on the usability of e‐books provided on smartphones and tablet PCs, which are typical touch‐based mobile devices. An experiment was carried out to see the effects of graphic metaphor and gesture interaction. This study evaluated reading speed, readability, similarity, and satisfaction for 16 combinations of e‐book interfaces (two Metaphor levels × four Display size and Screen modes × two Gesture levels). Overall, performance and subjective ratings showed better results on tablet PCs with larger fonts on a larger screen than on smartphones with smaller fonts on smaller screens. In the smartphone‐landscape mode, the effect of turning a page is a factor that hinders the speed of user reading. In contrast, the users’ readability, similarity, and satisfaction were higher when the page‐turning effect was provided. It showed faster reading speeds when a flicking interaction is provided on tablet PCs. From the standpoint of readability, the portrait mode was better on smartphones. Also, the tablet PC‐portrait mode was the most satisfactory.
A Short Sequence for the Iterative Synthesis of Fused Polyethers
Authors: Elustondo Frédéric , Chintalapudi Venkaiah , Clark J. Stephen
Published: August 2019

A simple and efficient four‐step sequence for the synthesis of fused polyether arrays has been developed. Cyclic ethers are installed by sequential alkynyl ether formation, carbocupration, ring‐closing metathesis and hydroboration with acidic workup. Crucially, the alkene required for the subsequent ring formation by ring‐closing metathesis is present in the substrate but is masked in the form of a vinylic silane, which prevents competitive metathesis of the side chain. Generation of the reactive alkene from the unreactive vinylic silane is accomplished by hydroboration and subsequent acid‐mediated Peterson elimination of the intermediate hydroxysilane.
Hall current and ion‐slip effects on free convection flow in a vertical microchannel with an induced magnetic field
Authors: Jha Basant K. , Malgwi Peter B.
Published: August 2019

The steady fully developed hydromagnetic flow of a viscous incompressible and electrically conducting fluid in a vertical microchannel has been studied taking into account the influence of Hall current, ion‐slip effects and an induced magnetic field. Exact solutions for the governing equations responsible for the flow formation are obtained by the method of the undetermined coefficient and presented graphically. It is found that in the presence of the ion‐slip effect, both primary and secondary components of fluid velocity increase with the Hall parameter for symmetric as well as asymmetric heating of the microchannel surfaces. Also, the magnetic field supports flow along the secondary flow direction while the reverse impact is observed along the primary flow direction.
Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers
Authors: Nome Marianne E. , Euceda Leslie R. , Jabeen Shakila , Debik Julia , Bathen Tone F. , Giskeødegård Guro F. , Taskén Kristin A. , Mælandsmo Gunhild M. , Halvorsen Bente , Yndestad Arne , Borgen Elin , Garred Øystein , Aukrust Pål , Ueland Thor , Engebraaten Olav , Kristensen Vessela N. , Tekpli Xavier
Published: August 2019

Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti‐vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine‐protein kinase erbB‐2‐negative breast cancers, we measured metabolites and inflammation‐related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation‐regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth‐differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.
Unfolded protein response‐mediated modulation of mesenchymal stem cells
Authors: Tavasolian Fataneh , Hosseini Ahmad Z. , Mirzaei Ali , Abdollahi Elham , Jandaghi Pouria , Soudi Sara , Naderi Mahmood , Saburi Ehsan , Momtazi‐Borojeni Amir Abbas , Johnston Thomas P. , Sahebkar Amirhossein
Published: August 2019

The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor‐6, inositol‐requiring enzyme‐1 (IRE1), and PKR‐like endoplasmic reticulum kinase, which up‐regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.
Understanding the effects of culture conditions in bacterial growth: A biochemical perspective using Raman microscopy
Authors: Mukherjee Ria , Verma Taru , Nandi Dipankar , Umapathy Siva
Published: August 2019

Rapid, sensitive and label‐free methods to probe bacterial growth irrespective of the culture conditions can shed light on the mechanisms by which bacteria adapt to different environmental stimuli. Raman spectroscopy can rapidly and continuously monitor the growth of bacteria under varied conditions. In this study, the growth of Escherichia coli in Luria broth (nutrient rich conditions) and minimal media with either glucose or glycerol as carbon source (nutrient limiting conditions) is profiled using Raman spectroscopy. Moreover, the study also gives insights into the altered bacterial biochemistry upon exposure to low‐ (25°C) and high‐temperature (45°C) stress. Raman spectral measurement was performed on bulk bacteria cultured under laboratory conditions. A detailed analysis of the spectra as a function of bacterial growth reveals changes in Raman band intensities/area of biomolecules such as DNA, proteins and lipids. We also report five novel ratiometric markers (I830/I810, I1126/I1100, I1340/I1440, I1207/I1240 and I1580/I1440) that can identify the phase of growth, independent of the culture condition. Unsupervised multivariate methods like Principal Component Analysis also corroborate the aforementioned markers of growth. Altogether, our findings highlight the potential of Raman spectroscopy in yielding universal biochemical signatures that may be indicative of stress and aging in a growth milieu.
Anti‐inflammation effects of injectable platelet‐rich fibrin via macrophages and dendritic cells
Authors: Zhang Jinglun , Yin Chengcheng , Zhao Qin , Zhao Zifan , Wang Jinyang , Miron Richard J. , Zhang Yufeng
Published: August 2019

Immune response to implantation materials plays a critical role during early local inflammation and biomaterial‐induced regeneration or restoration. A novel platelet concentrate termed i‐PRF (injectable platelet‐rich fibrin) has recently been developed without any additives by low centrifugation speeds. To date, scientists have investigated the capability of releasing growth factors to improve regeneration but have ignored whether i‐PRF can inhibit the inflammatory effect around the wound. The present study investigated the anti‐inflammation effects of i‐PRF on immune response‐related cells, especially macrophages and dendric cells. We found that i‐PRF reduced pro‐inflammatory M1 phenotype of macrophages and activated dendritic cells around muscle defect that was injected with bacterial suspension. Moreover, in vitro experiments showed similar results. i‐PRF deleted inflammatory response caused by lipopolysaccharide to some extent. We determined that TLR4, an activator of inflammatory stimulation and p‐p65, a key factor belongs to classical inflammatory related NF‐κB signal pathway, can be inhibited by use of i‐PRF. Results indicate the potential anti‐inflammatory role of i‐PRF during regeneration and restoration.
A Retrospective Review of the Efficiency of First‐Dose Therapeutic Drug Monitoring of Gentamicin, Amikacin, and Vancomycin in the Pediatric Population
Authors: Lim Wan Xuan Selina , Chua Wen Bing Brandon , Chua Jie Min , Lee Qianyu , Chan Jer Wei , Sultana Rehena , Poh Bao Hui
Published: August 2019

Therapeutic drug monitoring (TDM) has become standard clinical practice for gentamicin, amikacin, and vancomycin to optimize efficacy and reduce toxicity. TDM after the first dose of antibiotic was adopted in our institution. This study aims to evaluate if target therapeutic drug concentrations could be achieved more rapidly in patients with TDM performed after the first dose of gentamicin, amikacin, or vancomycin compared to TDM at steady state. A single‐center retrospective cohort study was conducted at KK Women's and Children's Hospital, Singapore. Patients aged 1 month to 18 years old who received amikacin, gentamicin, or vancomycin between October 2012 to March 2016 and had at least 2 serum drug concentrations done within the same dosing interval were included. The primary objective was to compare the time taken to achieve target serum drug concentrations between first‐dose and steady‐state TDM. A total of 334 patients on amikacin, 211 patients on gentamicin, and 140 patients on vancomycin were included. Using Kaplan‐Meier analysis, the median number of days to optimize therapy was significantly shorter after first‐dose TDM was performed for amikacin (first dose, 1.51 [95% confidence interval (CI), 1.44‐1.89] days vs steady state, 2.85 [95%CI, 2.50‐3.25] days; P < .01] and gentamicin (first dose, 1.66 [95%CI, 1.25‐2.08] days vs steady state, 3.54 [95%CI, 2.40‐4.75] days; P < .01] but not vancomycin (first dose, 1.34 [95%CI, 1.06‐1.52] days vs steady state, 1.42 [95%CI, 1.26‐1.59] days; P = .99]. First‐dose TDM for gentamicin and amikacin resulted in faster attainment of target serum concentrations but did not for vancomycin. Further validation of its impact on actual clinical outcomes may be required.
Reducing risk in the emergency department: a 12‐month prospective longitudinal study of radiographer preliminary image evaluations
Authors: Brown Cameron , Neep Michael J. , Pozzias Efrosini , McPhail Steven M.
Published: August 2019

Introduction

Innovations are necessary to accommodate the increasing demands on emergency departments whilst maintaining a high level of patient care and safety. Radiographer Preliminary Image Evaluation (PIE) is one such innovation. The purpose of this study was to determine the accuracy of radiographer PIE in clinical practice within an emergency department over 12 months.

Methods

A total of 6290 radiographic examinations were reviewed from 15 January 2016 to 15 January 2017. The range of adult and paediatric examinations incorporated in the review included the appendicular and axial skeleton including the chest and abdomen. Each examination was compared to the radiologist's report this allowed calculated mean sensitivity and specificity values to indicate if the radiographer's PIE was of a true negative/positive or false negative/positive value. Cases of no PIE participation or series’ marked as unsure for pathology by the radiographer were also recorded. This allowed mean sensitivity, specificity and diagnostic accuracy to be calculated.

Results

The study reported a mean ± 95% confidence level (standard deviation) for sensitivity, specificity, accuracy, no participation and unsure of 71.1% ± 2.4% (6.1), 98.4% ± 0.04% (0.9), 92.0% ± 0.68% (1.9), 5.1% (1.6) and 3.6% (0.14) respectively.

Conclusions

This study has demonstrated that the participating radiographers provided a consistent PIE service while maintaining a reasonably high diagnostic accuracy. This form of image interpretation can complement an emergency referrer's diagnosis when a radiologist's report is unavailable at the time of patient treatment. PIE promotes a reliable enhancement of the radiographer's role with the multi‐disciplinary team.
Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis
Authors: Figueiredo Eduardo A. , Loyola Leonor Casilla , Belangero Paulo S. , Campos Ribeiro‐dos‐Santos Ândrea Kely , Emanuel Batista Santos Sidney , Cohen Carina , Wajnsztejn Andre , Martins de Oliveira Adrielle , Smith Marília C. , Pochini Alberto de Castro , Andreoli Carlos V. , Ejnisman Benno , Cohen Moises , Leal Mariana F.
Published: August 2019

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full‐thickness tears of the supraspinatus (Nfemales = 130; Nmales = 81) and 567 age‐matched controls (Nfemales = 317; Nmales = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co‐morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT‐genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020
Supercritical fluid extraction in isolation of cyclitols and sugars from chamomile flowers
Authors: Al‐Suod Hossam , Ratiu Ileana‐Andreea , Krakowska‐Sieprawska Aneta , Lahuta Lesław , Górecki Ryszard , Buszewski Bogusław
Published: August 2019

The aim of the present study was to develop an optimization procedure for supercritical fluid extraction parameters, in order to obtain the highest possible yield of sugars and cyclitols from plant material. Response surface methodology based on Box‐Behnken design was applied to evaluate the effect of: temperature (40, 60, 80°C), pressure (100, 200, 300 bar), and co‐solvent (methanol) percentage (20, 25, 30%). As a result of the optimization process, we found that the highest amount of sugars (15.02 mg/gof dried material) and cyclitols (0.86 mg/g of dried material) was obtained when the following parameters were applied: 80°C, 228 bar, and 30% of methanol. Moreover, co‐solvent concentration and temperature had a higher influence onto the obtained amounts compared with the pressure.
Evaluation of Hemodynamic Changes in Fetuses With Isolated Mild‐to‐Moderate Ventriculomegaly by Transabdominal Ultrasound
Authors: Sun Lijuan , Zhang Lina , Zhang Na , Han Jijing , Li Zhen , Zhang Tiejuan , Yao Ling , Ma Yuqing , Wang Li , Liu Yan , Guo Cuixia , Wu Qingqing
Published: August 2019

Objectives

To investigate fetal hemodynamic alterations using transabdominal ultrasound in fetuses with isolated mild‐to‐moderate ventriculomegaly (VM).

Methods

Fetuses diagnosed with isolated mild‐to‐moderate VM by transabdominal ultrasound were evaluated for hemodynamic changes, including changes in fetal cardiac function, the umbilical artery, the ductus venosus, and the middle cerebral artery. The fetuses with isolated mild‐to‐moderate VM were divided into 2 groups, namely, before 32 weeks’ gestation (20 weeks–31 weeks 6 days) and after 32 weeks’ gestation (32–38 weeks), and matched to corresponding healthy control fetuses.

Results

The 53 fetuses with VM before 32 weeks had a longer mean isovolumetric relaxation time (IRT; mean ± SD, 42.9 ± 6.8 versus 40.4 ± 5.0 milliseconds; P < .05) and an apparently higher modified myocardial performance index 0.46 ± 0.06 versus 0.43 ± 0.05; P < .01) than the healthy control fetuses. The 43 fetuses with VM after 32 weeks had a significantly longer mean IRT (45.5 ± 6.7 versus 40.9 ± 7.2 milliseconds; P < .01) and a lower UA pulsatility index (0.81 ± 0.13 versus 0.89 ± 0.11; P < .01). The optimal cutoff levels for the IRT in the prediction of adverse perinatal outcomes were 40 and 43 milliseconds before and after 32 weeks, respectively (sensitivity, 100% versus 100%; specificity, 40.4% versus 50.0%; area under the curve, 0.601 versus 0.748; 95% confidence interval, 0.457–0.733 versus 0.590–0.869; P = .291 versus .005).

Conclusions

Some fetuses with isolated mild‐to‐moderate VM may have impaired cardiac function, characterized by a higher modified myocardial performance index or longer IRT. This finding might be useful for improving fetal surveillance.
Topical application of Cinnamon verum essential oil accelerates infected wound healing process by increasing tissue antioxidant capacity and keratin biosynthesis
Authors: Seyed Ahmadi Seyed Gharani , Farahpour Mohammad R. , Hamishehkar Hamed
Published: August 2019

Cinnamon essential oil is known to have antioxidant and antibacterial properties, which may accelerate, wound healing. This study was conducted to evaluate the effects of an ointment prepared from Cinnamon verum essential oil (C verum) in infected wound model. An experimentally excisional infected wound model was induced in mice. Circular excisional wound model of 5 mm surface area was surgically created and inoculated with 107 CFU of each of two bacterial strains of Staphylococcus aureus and Pseudomonas aeruginosa. The animals were divided into three groups and topically treated with soft yellow paraffin (control) and ointments containing 2% and 4% C verum. The mRNA levels of insulin‐like growth factor I (IGF‐1), fibroblast growth factor‐2 (FGF‐2) and vascular endothelial growth factor (VEGF), epidermal keratin, fibroblasts, fibrocytes, immune cells, and vascular distribution as well as epithelialization ratio were investigated in order to evaluate the effects of C verum on wound healing. Tissue total antioxidant capacity and malondialdehyde levels (MDA) were also evaluated. Topical administration of C verum remarkably shortened the inflammatory phase, increased fibroblast distribution, collagen deposition, and accelerated the cellular proliferation, reepithelialization and keratin synthesis. The mRNA levels of IGF‐1, FGF‐2 and VEGF were remarkably higher in C verum‐treated groups (especially 2%) in comparison control group. Topical administration of C verum increased antioxidant power and reduced MDA content in comparison to control animals. C verum accelerates wound healing by upregulating the IGF‐1, FGF‐2, and VEGF expression and increasing cell proliferation, collagen synthesis, and reepithelialization ratio.
Approximating the inverse and the Moore‐Penrose inverse of complex matrices
Authors: Cordero Alicia , Torregrosa Juan R. , Zafar Fiza
Published: August 2019

A parametric family of fourth‐order schemes for computing the inverse and the Moore‐Penrose inverse of a complex matrix is designed. A particular value of the parameter allows us to obtain a fifth‐order method. Convergence analysis of the different methods is studied. Every iteration of the proposed schemes involves four matrix multiplications. A numerical comparison with other known methods, in terms of the average number of matrix multiplications and the mean of CPU time, is presented.
Configurable triple wavelength semiconductor optical amplifier fiber laser using multiple broadband mirrors
Authors: Ahmad Harith , Azmy Nur F. , Azmi Atiqah N. , Zulkifli Mohd Z. , Ismail Mohd F.
Published: August 2019

A configurable, triple wavelength fiber laser based on broadband mirrors (BBMs) and an arrayed waveguide grating (AWG) is demonstrated. The laser uses a semiconductor optical amplifier (SOA) as the primary gain medium due to its inhomogeneous broadening property that allows for the generation high intensity lasing wavelengths. The combination of the AWG and BBMs allows for triple lasing wavelength outputs with channel spacing from 0.8 to 4.0 nm to be obtained. The generated output is adjustable between 1540.6 and 1548.6 nm. The proposed SOA‐based system is stable and can be used as a reserve laser source for wavelength division multiplexing systems.