bluuebunny/crossref_metadata_2025 huggingface dataset:
The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity
Authors: Secombe Kate R. , Coller Janet K. , Gibson Rachel J. , Wardill Hannah R. , Bowen Joanne M.
Published: August 2018

Chemotherapy‐induced gastrointestinal toxicity (CIGT) occurs in up to 80% of all patients undergoing cancer treatment, and leads to symptoms such as diarrhoea, abdominal bleeding and pain. There is currently limited understanding of how to predict an individual patient's risk of CIGT. It is believed the gut microbiome and its interactions with the host's innate immune system plays a key role in the development of this toxicity and potentially other toxicities, however comprehensive bioinformatics modelling has not been rigorously performed. The innate immune system is strongly influenced by the microbial environment and vice‐versa. Ways this may occur include the immune system controlling composition and compartmentalisation of the microbiome, the microbiome affecting development of antigen‐presenting cells, and finally, the NLRP6 inflammasome orchestrating the colonic host‐microbiome interface. This evidence calls into question the role of pre‐treatment risk factors in the development of gastrointestinal toxicity after chemotherapy. This review aims to examine evidence of a bidirectional interaction between the gut microbiome and innate immunity, and how these interactions occur in CIGT. In the future, knowledge of these interactions may lead to improved personalised cancer medicine, predictive risk stratification methods and the development of targeted interventions to reduce, or even prevent, CIGT severity.
A Transformative Justice Approach to Literacy Education
Authors: Winn Maisha T.
Published: August 2018

This department explores how teachers can sustain students’ multilingual literacies and reimagine literacy learning across multiple contexts in conversation with researchers, practitioners, and communities.
Reconciliation Through Education: A Review of Achieving Indigenous Student Success: A Guide for Secondary Classrooms
Authors: Montero M. Kristiina , Dénommé‐Welch Spy
Published: August 2018

This forum reviews a mix of resources to inform pedagogy and related educational practices that foreground representations of youths and their literacy practices within and outside of school.
Information flows and stock market volatility
Authors: Chua Chew Lian , Tsiaplias Sarantis
Published: August 2018

This study examines how news is distributed across stocks. A model is developed that categorizes a stock's latent news into normal and nonnormal news, and allows both types of news to be filtered through to other stocks. This is achieved by formulating a model that jointly incorporates a multivariate lognormal‐Poisson jump process (for nonnormal news) and a multivariate GARCH process (for normal news), in addition to a news (or shock) transmission mechanism that allows the shocks from both processes to impact intertemporally on all stocks in the system. The relationship between news and the expected volatility surface is explored and a unique news impact surface is derived that depends on time, news magnitude, and news type. We find that the effect of nonnormal news on volatility expectations typically builds up before dissipating, with the news transmission mechanism effectively crowding‐out normal news and crowding‐in nonnormal news. Moreover, in contrast to the standard approach for measuring leverage effects using asymmetric generalized autoregressive conditional heteroskedasticity models, we find that leverage effects stem predominantly from nonnormal news. Finally, we find that the capacity to identify positively or negatively correlated stock returns is ambiguous in the short term, and depends heavily on the behavior of the nonnormal news component.
High molecular weight fibroblast growth factor 2 induces apoptosis by interacting with complement component 1 Q subcomponent–binding protein in vitro
Authors: Hong Xiaobing , Yu Zelin , Chen Zhonglin , Jiang Hongyan , Niu Yongdong , Huang Zhanqin
Published: August 2018

Fibroblast growth factor 2 (FGF2) is a multifunctional cell growth factor that regulates cell proliferation, differentiation, adhesion, migration, and apoptosis. FGF2 has multiple isoforms, including an 18‐kDa low molecular weight isoform (lo‐FGF2) and 22‐, 23‐, 24‐, and 34‐kDa high molecular weight isoforms (hi‐FGF2). Hi‐FGF2 overexpression induces chromatin compaction, which requires the mitochondria and leads to apoptosis. Complement component 1 Q subcomponent–binding protein (C1QBP) plays an important role in mitochondria‐dependent apoptosis by regulating the opening of the mitochondrial permeability transition pore. However, the interaction between C1QBP and hi‐FGF2 and its role in hi‐FGF2–mediated apoptosis remain unclear. Here, we found that hi‐FGF2 overexpression induced depolarization of the mitochondrial membrane, cytochrome c release into the cytosol, and a considerable increase in C1QBP messenger RNA and protein expression. Furthermore, coimmunoprecipitation results showed that the mitochondrial protein, C1QBP, interacts with hi‐FGF2. C1QBP knockdown using small interfering RNA significantly decreased the localization of hi‐FGF2 to the mitochondria and increased the rate of apoptosis. Our results highlight a novel mechanism underlying hi‐FGF2–induced, mitochondria‐driven cell death involving the direct interaction between hi‐FGF2 and C1QBP and the upregulation of C1QBP expression.
Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138
Authors: Zhang Haifang , Li Hui , Liu Zhenguo , Ge Ang , Guo Enyu , Liu Shuxia , Chen Zhiping
Published: August 2018

Medulloblastoma is a primitive neuroectodermal‐derived brain tumor and the most common malignant brain tumor in children. Triptolide (TPL) is the major active component extracted from Tripterygium wilfordii Hook F. This study aimed to explore the effects of TPL on medulloblastoma cell proliferation, migration, and apoptosis, as well as the underlying possible molecular mechanism. Viability, proliferation, and apoptosis of Daoy cells were measured using cell counting kit‐8 assay, 5‐bromo‐2′‐deoxyuridine incorporation assay, and Guava Nexin assay, respectively. Cell migration was detected using two‐chamber transwell assay and wound healing assay. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was performed to determine the relative expression of microRNA‐138 (miR‐138) in Daoy cells. Cell transfection was used to change the expression of miR‐138 in cells. Western blot analysis was used to analyze the expression of key factors involved in cell apoptosis, cell migration, the phosphatidylinositol 3‐kinase (PI3K)/protein kinase 3 (AKT) pathway, and the Notch pathway in Daoy cells. We found that TPL significantly inhibited the viability, proliferation, and migration of Daoy cells but promoted Daoy cell apoptosis. The expression levels of matrix metalloproteinases (MMP)‐2 and MMP‐9 after TPL treatment were decreased. The expression of miR‐138 in Daoy cells after TPL treatment was increased. Suppression of miR‐138 obviously reversed the TPL‐induced Daoy cell proliferation, migration inhibition, and cell apoptosis enhancement, as well as the inactivation of the PI3K/AKT and Notch pathways. Cyclin‐dependent kinase 6 (CDK6) was a direct target gene of miR‐138, which might be involved in the antitumor effects of TPL on Daoy cells. In conclusion, our study verified that TPL exerted anticancer effects on medulloblastoma cells possibly via upregulating miR‐138 and inactivating the PI3K/AKT and Notch pathways.
Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer
Authors: Liu Beibei , Qi Xiaowei , Zhang Xiufen , Gao Danfeng , Fang Kai , Guo Zijian , Li Lihua
Published: August 2018

Adriamycin (ADM)‐based regimens are the most effective chemotherapeutic treatments for breast cancer. However, intrinsic and acquired chemoresistance is a major therapeutic problem. Our goal was to clarify the role of mediator complex subunit 19 (Med19) in chemotherapy resistance and to elucidate the related molecular mechanisms. In this study, ADM‐resistant human cells (MCF‐7/ADM) and tissues exhibited increased Med19 expression and autophagy levels relative to the corresponding control groups. Additionally, MCF‐7/ADM cells showed changes in two selective markers of autophagy. There was a dose‐dependent increase in the light chain 3 (LC3)‐II/LC3‐I ratio and a decrease in sequestosome 1 (P62/SQSTMl) expression. Furthermore, lentivirus‐mediated Med19 inhibition significantly attenuated the LC3‐II/LC3‐I ratio, autophagy‐related gene 3 (Atg3) and autophagy‐related gene 5 (Atg5) expression, P62 degradation, and red fluorescent protein‐LC3 dot formation after treatment with ADM or rapamycin, an autophagy activator. Furthermore, the antiproliferative effects of ADM, cisplatin (DDP), and taxol (TAX) were significantly enhanced after suppressing Med19 expression. Notably, the effects of Med19 on autophagy were mediated through the high‐mobility group box‐1 (HMGB1) pathway. Our findings suggest that Med19 suppression increased ADM chemosensitivity by downregulating autophagy through the inhibition of HMGB1 signaling in human breast cancer cells. Thus, the regulatory mechanisms of Med19 in autophagy should be investigated to reduce tumor resistance to chemotherapy.
Affinity maturation and characterization of the ofatumumab monoclonal antibody
Authors: Payandeh Zahra , Rajabibazl Masoumeh , Mortazavi Yousef , Rahimpour Azam , Taromchi Amir Hossein , Dastmalchi Siavoush
Published: August 2018

CD20 molecule, a phosphoprotein with 297 amino acids and four transmembrane domains, is a member of MS4A protein family. Anti‐CD20 antibodies such as ofatumumab, which have been developed for cancer treatment and has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. Rational engineering methods can be applied with reasonable success to improve functional characteristics of antibodies. Considering the importance of this issue, we have used in silico modeling approach for the improvement of ofatumumab monoclonal antibody. Four mutated variants of ofatumumab were developed and expressed in Chinese hamster ovary (CHO) cells along with the unmodified antibody. Analysis of affinity of the purified antibodies with CD20 showed significant improvement in antigen‐binding characteristics of one of the variants compared with the control antibody. This study represents the first step toward development of the second generation ofatumumab antibody with improved affinity.
Potential roles of microRNAs in redox state: An update
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein
Published: August 2018

Oxidative stress is an important underlying cause of many disease processes and may arise due to either increasing free radical generation or decreasing antioxidant defense systems. MicroRNAs (miRs) are 22‐nucleotide non‐coding RNAs that may regulate many intracellular processes; and, more recently, they have been implicated in the pathways for free radical generation leading to oxidative stress. However, conversely, there is evidence that miRs may have an antioxidant effect, thus miR expression may be critical for the maintenance of the normal redox state and cell homeostasis. This review addresses these discrepant and opposing miR actions on how they may modify and regulate the oxidative balance.
Genipin induces cell death via intrinsic apoptosis pathways in human glioblastoma cells
Authors: Ahani Narges , Sangtarash Mohammad Hossein , Houshmand Massoud , Eskandani Majid Alipour
Published: August 2018

Genipin, a compound derived from Gardenis jasminoides Ellis fruits, was demonstrated to be the specific uncoupling protein 2 (UCP2) inhibitor. UCP2 is a mitochondrial carrier protein that creates proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation from adenosine triphosphate (ATP) synthesis. Several studies revealed that UCP2 is broadly over‐expressed in leukemia, colorectal, lung, ovarian, prostate, testicular, and bladder cancers. However, the effect of genipin still needs to be elucidated in neurological malignancies. In this study, we investigated the anticancer effect of genipin in U87MG and A172 cell lines. The anticancer effect of genipin on these cell lines was measured by microculture tetrazoliumtest (MTT), Trypan blue exclusion, and colony formation assays, in the presence of various concentrations of genipin at different time intervals. We assessed apoptosis and measure intracellular reactive oxygen species (ROS) by flow cytometry. Expression of UCP2 and some of the genes involved in apoptosis was analyzed by real‐time quantitative polymerase chain reaction (PCR). Results of the MTT assay showed that genipin moderately reduced metabolic activity of both cell lines in dose‐ and time‐dependent manner. Result of Trypan blue exclusion test indicated that the viable cell count decreased in the treated group in a concentration‐dependent manner. Genipin also significantly decreased colony formation ability of these cells in a concentration‐dependent manner. Result of morphological changes showed that there were significant differences in cell number and morphology in treated groups as compared with the untreated groups. Flow cytometric analysis of U87MG and A172 cells with annexin V/propidium iodide staining, 48 hours after treatment with genipin, displays 22.4% and 26.1% apoptotic population, respectively, in treated cells, in comparison to 7.42% and 9.31% apoptotic cells of untreated cells. After treatment, UCP2 and B‐cell lymphoma 2 (BCL
2) genes are downregulated, and BCL
2 associated X protein, BCL
2 antagonist/killer, BCL
2 interacting killer, and Cytochrome c genes are upregulated. Genipin treatment increased mitochondrial ROS levels and also induced apoptosis through caspase‐3 upregulation. In conclusion, the antiproliferative effects of genipin on the growth of both glioblastoma cell lines have been shown in all of these assays, and genipin profoundly induced apoptosis in both cell lines via the UCP2‐related mitochondrial pathway through the induction of intracellular ROS.
NKCC1 promotes EMT‐like process in GBM via RhoA and Rac1 signaling pathways
Authors: Ma Haiwen , Li Tao , Tao Zhennan , Hai Long , Tong Luqing , Yi Li , Abeysekera Iruni R. , Liu Peidong , Xie Yang , Li Jiabo , Yuan Feng , Zhang Chen , Yang Yihan , Ming Haolang , Yu Shengping , Yang Xuejun
Published: August 2018

Glioblastoma is the most common and lethal primary intracranial tumor. As the key regulator of tumor cell volume, sodium‐potassium‐chloride cotransporter 1 (NKCC1) expression increases along with the malignancy of the glioma, and NKCC1 has been implicated in glioblastoma invasion. However, little is known about the role of NKCC1 in the epithelial‐mesenchymal transition‐like process in gliomas. We noticed that aberrantly elevated expression of NKCC1 leads to changes in the shape, polarity, and adhesion of cells in glioma. Here, we investigated whether NKCC1 promotes an epithelial–mesenchymal transition (EMT)‐like process in gliomas via the RhoA and Rac1 signaling pathways. Pharmacological inhibition and knockdown of NKCC1 both decrease the expressions of mesenchymal markers, such as N‐cadherin, vimentin, and snail, whereas these treatments increase the expression of the epithelial marker E‐cadherin. These findings indicate that NKCC1 promotes an EMT‐like process in gliomas. The underlying mechanism is the facilitation of the binding of Rac1 and RhoA to GTP by NKCC1, which results in a significant enhancement of the EMT‐like process. Specific inhibition or knockdown of NKCC1 both attenuate activated Rac1 and RhoA, and the pharmacological inhibitions of Rac1 and RhoA both impair the invasion and migration abilities of gliomas. Furthermore, we illustrated that NKCC1 knockdown abolished the dissemination and spread of glioma cells in a nude mouse intracranial model. These findings suggest that elevated NKCC1 activity acts in the regulation of an EMT‐like process in gliomas, and thus provides a novel therapeutic strategy for targeting the invasiveness of gliomas, which might help to inhibit the spread of malignant intracranial tumors.
Circular RNA of vimentin expression as a valuable predictor for acute myeloid leukemia development and prognosis
Authors: Yi Yun‐Yun , Yi Jing , Zhu Xin , Zhang Jing , Zhou Jiao , Tang Xi , Lin Jiang , Wang Peng , Deng Zhao‐Qun
Published: August 2018

The focus of this study was to investigate the expression status of Circ‐vimentin (VIM) and further analyze its pathogenesis and clinical significance in acute myeloid leukemia (AML) patients. Real‐time quantitative polymerase chain reaction was carried on Circ‐VIM in 113 AML patients and 42 healthy controls. Circ‐VIM was significantly upregulated in AML compared with control and was positively correlated with white blood cells (WBC) count. Receiver operating characteristic curve analysis indicated that the performance of Circ‐VIM expression could serve as a promising biomarker for differentiating AML patients from controls. Significant correlations of Circ‐VIM expression were found with WBC and French–American–British classifications. Survival analyses further showed that over‐expressed Circ‐VIM were associated with markedly shorter overall survival (OS) and leukemia‐free survival (LFS) in whole‐cohort AML, nonacute promyelocytic leukemia AML and cytogenetically normal‐AML patients. Multivariate analysis also disclosed that Circ‐VIM over‐expression was an independent poor prognostic factor for OS and LFS in AML patients. Remarkably, Pearson correlation analysis evidenced that the expression of Circ‐VIM was positively correlated with VIM expression in all AML patients. These results indicated that overexpression Circ‐VIM could serve as a significant biomarker.
Segmentation pattern of zebrafish caudal fin is affected by developmental temperature and defined by multiple fusions between segments
Authors: Christou Maria , Iliopoulou Maria , Witten Paul Eckhard , Koumoundouros George
Published: August 2018

Caudal‐fin lepidotrichia is composed of numerous segments, which are linked to each other by intersegmental joints. During fish growth, lepidotrichia elongate by the addition of new segments at their distal margin, whereas the length of each segment remains constant after it is formed. In the present paper, we examined whether the water temperature affects the segmentation pattern of the juvenile and adult caudal fin. For this purpose, zebrafish (Danio rerio) embryos and larvae were exposed to three different temperature conditions (24°C, 28°C, and 32°C) from the pharyngula stage (1 day postfertilization [dpf]) to metamorphosis, whereas the control temperature (28°C) was applied to all the groups before and after this period. Results demonstrated that water temperature had a significant effect on the length of the segments of each lepidotrichium, at both the juvenile and adult stages. Moreover, at higher temperatures, there was a significant proximal shift of the position of the first bifurcation of the second lepidotrichium of the dorsal lobe. At all the experimental conditions, the length of proximal segment was not constant during fish growth, but it followed a discontinuous saltatory growth. Histological analysis of the proximal lepidotrichia segments revealed that the observed apparent growth of segments is the result of fusions between segments. Fusion occurs not by mineralization of the intersegmental joints, but by bone deposition around the joints.
Arc index of spatial graphs
Authors: Lee Min Jung , No Sungjong , Oh Seungsang
Published: August 2018

Bae and Park found an upper bound on the arc index of prime links in terms of the minimal crossing number. In this paper, we extend the definition of the arc presentation to spatial graphs and find an upper bound on the arc index of any spatial graph as where is the minimal crossing number of , is the number of edges, and is the number of bouquet cut‐components. This upper bound is lowest possible.
New radical methods for the potential synthesis of carbon‐13 and carbon‐14 labeled complex products
Authors: Maxwell Brad D.
Published: August 2018

The isotopic labeling of molecules for agrichemical and pharmaceutical uses is becoming more challenging as molecules become larger, involve more stereochemistry, and as intellectual property rights become more complex. As such, isotope chemists need to continually add new isotopic methods to their armamentarium to successfully label complex molecules with carbon‐13 and carbon‐14. Recently, there has been a surge in the use of radicals to form new carbon‐carbon bonds and for the incorporation of functional groups which can be used to incorporate isotopically labeled carbons. This review will describe some potential new radical methods for incorporating isotopically labeled carbon into complex molecules or into substrates that can be attached to late stage intermediates to generate labeled products.
CycloBranch: An open tool for fine isotope structures in conventional and product ion mass spectra
Authors: Novák Jiří , Škríba Anton , Zápal Jakub , Kuzma Marek , Havlíček Vladimír
Published: August 2018

Within the growing community of Fourier transform mass spectrometry users, the identification of fine isotope structure has become an indispensable method for molecular formula determination. In this work, the fine isotope envelopes for accessing the mutual ratio of 2 closely related pyoverdines in a mixture were used. Bacterial siderophores pyoverdines D and E cannot be easily separated via liquid chromatography‐mass spectrometry because their structures differ in (de)amidation at the respective chromophore parts only. Their mutual ratio was determined in a mixture via nuclear magnetic resonance spectroscopy and semiquantitative mass spectrometry using our open‐source software CycloBranch, which represents a genuine free tool supporting the determination of fine isotope structures in both conventional and product ion mass spectra. Native Bruker, Thermo, and Waters data formats are supported in addition to XML and plain text formats.
Issues and challenges in defining a heat wave: A Mediterranean case study
Authors: Barcena‐Martin Elena , Molina Julian , Ruiz‐Sinoga Jose Damian
Published: August 2018

We evaluated three definitions of heat wave (HW) and demonstrate that selection of the reference period and air temperature threshold used in the definition can affect the reported frequency of HWs. First, we propose an alternative definition of HW that is based on a moving reference period and specific air temperatures threshold for each calendar date. Then, we present a case study using data from five observatories in Malaga Province (Spain) from 1971 to 2016. We assessed the effect of a moving reference period (rather than a fixed reference period) and the definition of daily air temperatures threshold on the identification of anomalies in the definition of a HW. The results indicate that HWs can occur throughout the year. Finally, we propose incorporation of minimum daily air temperatures in two alternative definitions of HW. Our results indicate a high frequency of HWs in the summer months, in which HWs are mainly due to anomalous high Tmin and more frequent HWs in which maximum and minimum daily air temperature are exceeded from 2014 onwards. These new methods of defining a HW provide more accurate assessments of thermal discomfort.
Added value of dynamical downscaling for hydrological projections in the Chungju Basin, Korea
Authors: Lee Moon‐Hwan , Lu Mengqian , Im Eun‐Soon , Bae Deg‐Hyo
Published: August 2018

In this study, we assess whether dynamical downscaling using a regional climate model (RCM) would provide added value against the driving global climate model (GCM) and whether a statistically bias‐corrected GCM could be used as an alternative to a bias‐corrected RCM for assessing the hydrological response to climate change. The target region is the Chungju Basin in Korea, which is characterized by complex geographical features. The analysis focuses on runoff simulations driven by raw outputs and bias‐corrected outputs from the HadGEM2‐AO and RegCM4, which are used to generate national standard climate change scenarios throughout the Korean Peninsula. Statistical methods, such as linear scaling and quantile mapping, improve the performance in precipitation simulations and effectively correct the systematic biases seen with the climatological means of the HadGEM2‐AO and RegCM4. Although there is no relevant difference between the bias‐corrected HadGEM2‐AO and RegCM4 in terms of long‐term averaged climatology, the bias‐corrected RegCM4 performs better in capturing the dominant mode of runoff variability and hydrological extremes (e.g., floods measured by 1‐day maximum runoff and droughts measured by the standardized runoff index). Because the magnitude of the bias correction factor tends to influence the preservation of future change signals derived from raw and bias‐corrected outputs, the HadGEM2‐AO, which requires a large bias correction factor to compensate for poor performance, produces future changes in high flows with low coherence between the raw and bias‐corrected projections.
Changes in the Raman spectra of monolayer MoS2 upon thermal annealing
Authors: Kim Ho‐Jong , Kim Daehee , Jung Suyong , Bae Myung‐Ho , Yun Yong Ju , Yi Sam Nyung , Yu Jeong‐Seon , Kim Jong‐Hyun , Ha Dong Han
Published: August 2018

Defects have crucial effects on the electronic and optoelectronic properties of two‐dimensional materials. In this work, we measured the changes in the Raman spectra and electrical conductance of monolayer molybdenum disulfide (MoS2) with increasing defects via thermal annealing in a reducing atmosphere. Raman spectra of the basal plane MoS2 on SiO2 differed from those of the edge and revealed intricate changes upon annealing up to 550°C due to the substitution of adsorbed molecules and the creation of highly concentrated defects. On the other hand, MoS2 on hexagonal boron nitride (h‐BN) presented homogenous Raman spectra over the entire area and showed no noticeable changes in its Raman spectra upon annealing. For MoS2 on h‐BN, the charge transfer between MoS2 and adsorbed molecules and the number of defects created by annealing up to 550°C are not sufficient to change the Raman spectra. The distinct behaviors of the two sample spectra are ascribed to different substrate‐induced doping and interfacial adhesion strengths.
Osteoarthritis and intervertebral disc degeneration: Quite different, quite similar
Authors: Rustenburg Christine M.E. , Emanuel Kaj S. , Peeters Mirte , Lems Willem F. , Vergroesen Pieter‐Paul A. , Smit Theodoor H.
Published: August 2018

Intervertebral disc degeneration describes the vicious cycle of the deterioration of intervertebral discs and can eventually result in degenerative disc disease (DDD), which is accompanied by low‐back pain, the musculoskeletal disorder with the largest socioeconomic impact world‐wide. In more severe stages, intervertebral disc degeneration is accompanied by loss of joint space, subchondral sclerosis, and osteophytes, similar to osteoarthritis (OA) in the articular joint. Inspired by this resemblance, we investigated the analogy between human intervertebral discs and articular joints. Although embryonic origin and anatomy suggest substantial differences between the two types of joint, some features of cell physiology and extracellular matrix in the nucleus pulposus and articular cartilage share numerous parallels. Moreover, there are great similarities in the response to mechanical loading and the matrix‐degrading factors involved in the cascade of degeneration in both tissues. This suggests that the local environment of the cell is more important to its behavior than embryonic origin. Nevertheless, OA is widely regarded as a true disease, while intervertebral disc degeneration is often regarded as a radiological finding and DDD is undervalued as a cause of chronic low‐back pain by clinicians, patients and society. Emphasizing the similarities rather than the differences between the two diseases may create more awareness in the clinic, improve diagnostics in DDD, and provide cross‐fertilization of clinicians and scientists involved in both intervertebral disc degeneration and OA.
Rapid quantification of aloin A and B in aloe plants and aloe‐containing beverages, and pharmaceutical preparations by microchip capillary electrophoresis with laser induced fluorescence detection
Authors: Xiao Meng‐Wei , Bai Xiao‐Lin , Liu Yi‐Ming , Yang Li , Hu Ya‐Dong , Liao Xun
Published: August 2018

A microchip capillary electrophoresis coupled with laser induced fluorescence detection method for the fast determination of aloin was developed and comprehensively applied for the quantification of aloin A and B present in seven aloe plant species, 42 aloin‐containing crude drugs, ten aloe pharmaceutical preparations, and four aloe gel‐containing functional foods. The excitation and emission wavelengths for detection of both aloins were set at 473 and 520 nm, respectively. Sample analysis on a 35 mm length of glass microchip channel was completed within 40 s. An interference study indicated that the other main anthraquinones present in the samples did not interrupt with the target aloins detection, demonstrating the good selectivity of this method. It is demonstrated that this method is fast, facile, and specific for determination of aloin A and B from matrix samples which can be applied to the quality control of a wide varieties of aloe species and aloe‐derived products.
Molecularly imprinted polymer based diffusive gradients in thin‐films for in situ selective sampling and determination of ciprofloxacin
Authors: Li Yanan , Chen Hong , Zhu Yu , Zhang Tingting , Gu Jiali , Xu Yongxia , Li Jianrong
Published: August 2018

A technique of diffusive gradients in thin films with ciprofloxacin‐molecularly imprinted polymers as the binding agent was developed for in situ selective sampling and measurement of ciprofloxacin in water. The ciprofloxacin uptake by the method increased linearly with time (r2 = 0.998) with a recovery of 96.8% in synthetic solution. The method performance was not dependent on solution pH over the pH range of 2–11 and ionic strength range from 1 × 10−4 to 0.5 mol/L sodium nitrate. The binding agent has a higher adsorption affinity for ciprofloxacin than for other drug residues, such as norfloxacin, chloramphenicol, and malachite green. The concentration of ciprofloxacin in river water determined by this method was 0.52 ± 0.3 μg/L, and the recoveries of ciprofloxacin were 96.1–102.0%.
Patterns, pace, and processes of water‐quality variability in a long‐studied estuary
Authors: Cloern James E.
Published: August 2018

Abstract

Environmental time series have rich information content that is invaluable for measuring and understanding changes over time and guiding policies to manage change. I extracted information from measurements of 10 water‐quality constituents in upper San Francisco Bay from 1975 to 2016, one of the longest observational records in a U.S. estuary. Changes were detected at every time scale captured by monthly sampling. Long‐term trends included increased ammonium (+53%), nitrate + nitrate (+50%), silicate (+14%), Secchi depth (+42%), and decreased chlorophylla(Chla) (−74%) and suspended particulate matter (−45%). Changes at the decadal scale included abrupt shifts (Chla, nitrate + nitrite) and oscillations between shorter trends of increase and decrease (Secchi depth, phosphate). Long‐term trends were not expressed equally across all seasons, and seasonal patterns of change varied across constituents. These examples illustrate key features of environmental variability at the land–sea interface: (1) water‐quality components change continually at time scales from months to decades; (2) patterns of seasonal, multiyear, and multidecadal change are complex and vary across constituents; (3) primary drivers of change are freshwater inflow, the master regulator of estuarine dynamics, and human activities such as river damming, water diversions, wastewater discharge, environmental policies, and species introductions; (4) extracting the full information content of time series requires multiple analyses, each revealing a different layer of insight into how changes develop over time; (5) water‐quality variability is nonstationary, so future changes cannot be forecast reliably; (6) repeated observation is an essential method of Earth system science with applications in the design and performance measures of environmental policies.
Topical delivery of vismodegib using ablative fractional laser and micro‐emulsion formulation in vitro
Authors: Olesen Uffe H. , Clergeaud Gael , Lerche Catharina M. , Andresen Thomas L. , Haedersdal Merete
Published: August 2018

Background and Objective

Hedgehog inhibitors such as vismodegib are targeted drugs widely used for the treatment of basal cell carcinomas; however, their use is significantly limited by frequent systemic side effects due to oral administration route. We aim to use ablative fractional laser (AFL) to enable the topical delivery of vismodegib to relevant dermal depths.

Materials and Methods

Pig skin was treated in vitro with a fractional 10,600 nm CO2 laser at 0 or 80 mJ/microbeam and exposed to vismodegib (6.4 mmol/L) in Franz‐diffusion cells for 0.5, 4, and 24 hours (n = 54 samples), either formulated in a micro‐emulsion composed of soybean oil and Tween 80 or dissolved in ethanol as vehicle control. Vismodegib biodistribution was studied at specific skin depths from 0 to 1,800 µm (incremental steps of 300 µm) by mass spectrometry.

Results

Combination of AFL and vismodegib emulsion substantially enhanced the delivery of drug into the skin. Emulsion formulation alone yielded higher vismodegib skin concentrations compared to vehicle control in superficial and mid‐dermis (0–900 µm, P = 0.002–0.015). The over‐all highest concentration found (554.5 µmol/L) was reached at 24 hours in superficial (0–300 µm) AFL exposed skin, 7.6‐fold higher than vehicle control (P = 0.002) and 9.7–101.6 fold higher than previously reported steady‐state plasma concentrations in patients treated with oral vismodegib (5.5–56.9 µmol/L). Compared to intact skin, AFL exposure significantly increased skin concentrations of vismodegib even in deep skin layers (24 h, 900–1,800 µm, emulsion: 8.7–74.3 µmol/L vs. 0.0–0.0 µmol/L, P = 0.004–0.048; vehicle control: 23.7–50.6 µmol/L vs. 0.0–1.6 µmol/L, P = 0.002). The total delivery of vismodegib‐emulsion into mid‐deep dermal skin layers from 600 to 1,800 µm was for AFL exposed skin 8.2 fold higher than intact skin. Also, delivery of emulsion vismodegib by AFL was time‐dependent as seen by the continuous increase in concentrations found over time, with highest uptake detected after 24 hours (4–24 hours, 0–900 µm, P = 0.002–0.004).

Conclusion

AFL enhances topical delivery of micro‐emulsion formulated vismodegib, reaching concentrations similar to or above plasma concentrations previously reported in patients receiving oral vismodegib. Lasers Surg. Med. 51:79–87, 2019. © 2018 Wiley Periodicals, Inc.
Efficacy and safety of picosecond 755‐nm alexandrite laser with diffractive lens array for non‐ablative rejuvenation in Chinese skin
Authors: Wat Heidi , Yee‐nam Shek Samantha , Yeung Chi Keung , Chan Henry Hin‐lee
Published: August 2018

Background and Objectives

The picosecond alexandrite laser with diffractive lens array (DLA) offers the dual advantages of a picosecond pulse duration and the fractionated delivery of laser energy. This study explores the efficacy and safety of the DLA for treatment of multiple aesthetic concerns associated with photoaging of the face including skin texture irregularities, dyspigmentation, enlarged pore size, rhytides, and skin laxity.

Methods

This prospective, evaluator‐blinded trial enrolled Fitzpatrick skin type III–IV patients with mild to moderate signs of facial photoaging. Patients received six full face treatments at 4 week intervals for a total of 107 treatments. Standardized photography was obtained at baseline and at 1, 2, and 3 month follow‐up visits. Two independent blinded evaluators rated each of the five signs of photoaging on a 10‐point visual analog scale (VAS) at each follow‐up visit compared to baseline. A global aesthetic improvement score was also assigned at each follow‐up visit. Secondary outcomes included patient‐rated pain and heat sensation on a 10‐point VAS, and overall satisfaction. Adverse events were noted after each treatment and at each follow‐up visit.

Results

A total of 18 Chinese patients age 35–59 completed the study. A statistically significant improvement in skin texture and dyspigmentation scores was noted at the 1 month follow‐up that was sustained at 3 months. No significant improvements wer­­e observed in pore size, rhytides, or skin laxity. The mean pain score was 5.1 ± 2 and mean heat sensation was 3.6 ± 2.1. Expected transient erythema and edema occurred in 95.3% (102/107) and 1.9% (2/108) of treatments, respectively, and resolved in hours. No incidences of post‐inflammatory hyperpigmentation (PIH) were noted at the 1, 2, and 3 month visits.

Conclusion

The 755‐nm picosecond laser with DLA is a safe and effective non‐ablative modality for targeting facial skin texture irregularities and dyspigmentation in Chinese skin. Patients tolerated the treatment well with adverse effects limited to transient erythema and edema. Lasers Surg. Med. 51:8–13, 2019. © 2018 Wiley Periodicals, Inc.
In‐depth analysis of antibacterial mechanisms of laser generated shockwave treatment
Authors: Yao William , Kuan Edward C. , Chung Young Hun , Francis Nathan C. , St. John Maie A. , Taylor Zachary D. , Grundfest Warren S.
Published: August 2018

Background and Objectives Laser generated shockwave (LGS) is a novel modality for minimally invasive disruption of bacterial biofilms. The objectives of this study are to determine the mechanisms behind LGS treatment and non‐biofilm effects on bacterial disruption, including (1) comparing bacterial load with and without LGS in its planktonic form and (2) estimating bacterial cell permeability following LGS.

Study Design/Materials and Methods For the first study, planktonic S. epidermidis were treated with gentamicin (0, 8, 16, 32, 64 μg/ml) with and without LGS (1064 nm Nd:YAG laser, 110.14 mJ/mm2, pulse duration 9 ns, spot size 3 mm, n = 8/group), and absorbances at 600 nm compared. For the second study, four samples of planktonic S. epidermidis were treated with LGS (same settings). Propidium iodide (PI) uptake via flow cytometry as a measure of cell permeability was measured at 0, 10, and 20 minutes following LGS.

Results

In comparing corresponding gentamicin concentrations within both LGS‐treated samples and controls at 0 hours, there were no differences in absorbance (P = 0.923 and P = 0.814, respectively). Flow cytometry found modest PI uptake (10.4 ± 2.5%) immediately following LGS treatment, with time‐dependent increase and persistence of the signal at 20 minutes (R2 = 0.449, P = 0.048).

Conclusion

Taken together, LGS does not appear to have direct bacteriocidal properties, but rather by allowing for biofilm disruption and bacterial cell membrane permeabilization, both of which likely increase topical antibiotic delivery to pathogenic organisms. Insight into the mechanisms of LGS will allow for improved clinical applications and facilitate safe and effective translation of this technology. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.
A Validated Score Predicts Acute Kidney Injury and Survival in Patients With Alcoholic Hepatitis
Authors: Sujan Ravi , Cruz‐Lemini Monica , Altamirano Jose , Simonetto Douglas A. , Maiwall Rakhi , Axley Page , Richardson Taylor , Desai Vivek , Cabezas Joaquin , Vargas Victor , Kamath Patrick S. , Shah Vijay H. , Sarin Shiv K. , Bataller Ramon , Singal Ashwani K.
Published: August 2018

Identifying patients at high risk for acute kidney injury (AKI) during hospitalization among patients admitted with severe alcoholic hepatitis (AH) is an unmet clinical need. We performed a multicentric prospective cohort study using data from 4 different cohorts on well‐characterized patients hospitalized with severe AH. Data collected on 773 AH patients from 4 cohorts across the globe were randomly split into test (n = 390) and validation (n = 383) cohorts. We found that 32% of the patients developed inpatient AKI in the test cohort. Approximately 60% of patients met criteria for systemic inflammatory response syndrome (SIRS) at admission. Hepatic encephalopathy, SIRS, and Model for End‐Stage Liver Disease score at admission predicted inpatient AKI with odds ratios of 3.86, 2.24, and 1.14, respectively. The AKI risk score developed using these predictors stratified risk of inpatient AKI to low (score <3), moderate (3‐4), and high (>4). These findings were replicated in the validation cohort. In the whole study cohort, patients with AKI had a lower 90‐day survival (53% versus 77%; P < 0.001). Those with AKI risk score of >4 had significantly lower 90‐day survival as compared with those with risk scores between 3 and 4 and <3 (47% versus 68% versus 88%; P < 0.001). In conclusion, AKI occurs frequently in AH patients and negatively impacts short‐term mortality. The AKI risk score is useful in identifying patients at high risk for inpatient AKI and may be useful for developing new therapeutic strategies to prevent AKI in patients with AH.
Sensitivity Analysis of Single‐Phase Isothermal Free Radical–Induced Grafting of Polyethylene
Authors: Hernández‐Ortiz Julio C. , Van Steenberge Paul H. M. , Duchateau Jan N. E. , Toloza Carolina , Schreurs Fons , Reyniers Marie‐Françoise , Marin Guy B. , D’hooge Dagmar R.
Published: August 2018

Radical‐induced grafting of polyethylene involves many reactions such as initiator dissociation, hydrogen abstraction, graft chain initiation, graft (de)propagation, crosslinking, and homo(de)polymerization. To ensure a successful grafting, both the reaction rate and degree of grafting functionalization need to be sufficiently high, implying a design of the process conditions. In the present article, assuming isothermal conditions and a single‐phase reactive system, it is demonstrated that the grafting kinetics is influenced by the hydrogen abstraction rate coefficient, the depropagation equilibrium coefficient Keq
, and the initial mass fractions of monomer, initiator, and polyolefin. It is shown that the reaction extent is a consequence of the interplay of the initial monomer mass fraction and Keq
, and the average grafting length is determined by grafting “from” and “to,” with longer grafts being formed through grafting “to.” Close to equilibrium, the average graft length decreases and the crosslinking density increases provided that initiator is left. Moreover, the chain length distribution of the virgin polyolefin strongly influences the molecular arrangement of the grafting points along the polyolefin chains. This can be demonstrated from the hydrogen abstraction reaction event history of polyolefin chains.
Solving MCDM problems based on combination of PACMAN and LINMAP
Authors: Kashef Mojtaba , Safari Hossein , Maleki Meysam , Cruz‐Machado Virgilio
Published: August 2018

Multicriteria decision‐making approaches are receiving more and more attention with the increase of expectations from decision makers in variety of fields. The growth in applying such approaches has led to identifying their strengths as well as their shortcomings. Passive and active compensability multicriteria analysis (PACMAN) is one of the frequently used approaches which has the capability to consider compensation in describing intercriteria relations in multicriteria decision‐making problems. This methodology is well formed and rationally structured in the first two phases, in which the problem is formulated and the decisive indices are obtained. However, it has some shortcomings in the idea of concluding the process of solution in its last phase. In the current study, we review the methodology, discuss its possible shortcomings, and propose an approach based on the combination of PACMAN and linear programming technique for multidimensional analysis of preference (LINMAP). The proposed approach which is taken to evaluate the PACMAN and LINMAP methodologies can help researchers and decision makers who seek an accurate perspective to evaluate a multicriteria decision‐making methodology.
Evaluation of long‐term functional donor‐site morbidity after deep circumflex iliac crest artery bone flap harvest
Authors: Rendenbach Carsten , Goehler Friedemann , Hansen Lara , Kohlmeier Carsten , Amling Michael , Hanken Henning , Beck‐Broichsitter Benedicta , Heiland Max , Riecke Bjoern
Published: August 2018

Purpose

Free flap surgery can be associated with donor‐site morbidity. The purpose of this study was to analyze long‐term functional outcomes at the donor site after deep circumflex iliac artery (DCIA) bone flap harvesting.

Methods

Fourteen patients (8 men and 6 women, mean age 53.9 years; range 22–87 years) with mandible resection (8 carcinomas, 4 ameloblastomas, 1 osteonecrosis, and 1 myxofibroma) and DCIA flap reconstruction were included in an observational study. Ranges of motion in the hip and lumbar spine, Harris hip score (HHS), jumping mechanography, chair rising, and balance testing were performed on a ground force reaction plate (Leonardo Mechanograph, Novotec Medical GmbH, Germany). The primary outcome was the Esslinger fitness index (EFI, maximum peak power in W/kg normalized to age and gender).

Results

Functional assessment was performed preoperatively and 29.0 months postoperatively (range 12–51 months). Mean DCIA flap length was 6.3 cm (range 3.3–10.1 cm). Jaw reconstruction was successful in all cases. HHS (99.2 vs. 97.7 points, P = .004) and all ranges of motion in the lumbar spine and hip joint except for dorsal extension were significantly reduced postoperatively (range −4° to −11.0°). There was no significant difference between pre‐ and postoperative EFI (77.9% vs. 74.28%, P = .591) and body sway (1.25 cm2 vs. 2.01 cm2, P = .806). Sensory deficits (n = 5), load dependent pain (n = 3), and limitations of daily activities (n = 3) were subjective complaints.

Conclusion

Functional donor site morbidity after DCIA harvesting can be expected to be low in the long‐term.
Extracellular dynamics of early HIV infection
Authors: Capistrán Marcos A. , Núñez‐López Mayra , Rempala Grzegorz A.
Published: August 2018

In this paper, we explore the interplay of virus contact rate, virus production rates, and initial viral load during early HIV infection. First, we consider an early HIV infection model formulated as a bivariate branching process and provide conditions for its criticality R0 > 1. Using dimensionless rates, we show that the criticality condition R0 > 1 defines a threshold on the target cell infection rate in terms of the infected cell removal rate and virus production rate. This result has motivated us to introduce two additional models of early HIV infection under the assumption that the virus contact rate is proportional to the target cell infection probability (denoted by
). Using the second model, we show that the length of the eclipse phase of a newly infected host depends on the target cell infection probability, and the corresponding deterministic equations exhibit bistability. Indeed, occurrence of viral invasion in the deterministic dynamics depends on R0 and the initial viral load V0. If the viral load is small enough, eg, V0 ≪ θ, then there will be extinction regardless of the value of R0. On the other hand, if the viral load is large enough, eg, V0 ≫ θ and R0 > 1, then there will be infection. Of note, V0≈θ corresponds to a threshold regime above which virus can invade. Finally, we briefly discuss between‐cell competition of viral strains using a third model. Our findings may help explain the HIV population bottlenecks during within‐host progression and host‐to‐host transmission.