bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrofluorimetric investigation with green analytical procedures for estimation of bambuterol and terbutaline: Application to pharmaceutical dosage forms and content uniformity testing
Authors: Abo El Abass Mohamed Samah , El‐Awady Mohamed I.
Published: November 2018

Bambuterol (BAM) and terbultaline (TER) are well known and effective bronchodilators. In this article highly sensitive, green and cost‐effective spectrofluorimetric methods are designed to determine low concentrations of such drugs. The proposed methods are based on an investigation of the native fluorescence properties of aqueous solutions of BAM at 298 nm after excitation at 263 nm and of TER at 313 nm after excitation at 275 nm. Under optimum conditions, the plots of the relative fluorescence intensity versus concentration were rectilinear over the range 0.1–1.2 μg/mL for BAM and 0.05–0.5 μg/mL for TER with a limit of quantitation of 0.067 μg/mL for BAM and 0.018 μg/mL for TER. The methods are simple and hence suitable for application to the quantification of BAM and TER in syrups and tablets without interference from common excipients. Furthermore, based on United States Pharmacopeia (USP) guidelines, the application was extended to determine the content uniformity of the cited drugs in low dose tablets. The developed methods were fully validated according to the guidelines of the International Conference on Harmonization (ICH).
Visible Light‐Driven, One‐pot Amide Synthesis Catalyzed by the B12 Model Complex under Aerobic Conditions
Authors: Tian Hui , Shimakoshi Hisashi , Ono Toshikazu , Hisaeda Yoshio
Published: November 2018

A visible light responsive catalytic system with the B12 complex as the catalyst and [Ir(dtbbpy)(ppy)2]PF6 as the photosensitizer was developed. It provides a convenient and efficient way to synthesize amides. Based on this method, trichlorinated organic compounds were converted into amides in the presence of an amine under aerobic conditions at room temperature in a one‐pot procedure. Various trichlorinated organic compounds and an amine source, such as primary, secondary, and cyclic amines, have been evaluated for this transformation, providing the expected products in moderate to excellent yields. Notably, product formation depended on the reaction atmosphere where the amide was obtained under aerobic conditions while partially dechlorinated products were obtained under anaerobic conditions. As this protocol is free from hazardous reagents, extra additives, noble metals, and dangerous gas, the present method provides a novel and efficient approach for amide synthesis under mild and easily controlled conditions.
Disability and identity: An introduction
Authors: LoGiudice Joseph A.
Published: November 2018

Since the inception of the Rehabilitation Act of 1973, the idea of disability in university settings has mushroomed into the creation of fully fledged offices that center on disability services for individuals with disabilities. Despite those services being required under disability laws and necessary to ensure equal access and full participation for people with disabilities, their existence falls significantly short of the evolution of the epistemology of disability itself.
Dysregulated Translation in Neurodevelopmental Disorders: An Overview of Autism‐Risk Genes Involved in Translation
Authors: Chen Yan‐Chu , Chang Yu‐Wei , Huang Yi‐Shuian
Published: November 2018

Regulated local translation—whereby specific mRNAs are transported and localized in subcellular domains where they are translated in response to regional signals—allows for remote control of gene expression to concentrate proteins in subcellular compartments. Neurons are highly polarized cells with unique features favoring local control for axonal pathfinding and synaptic plasticity, which are key processes involved in constructing functional circuits in the developing brain. Neurodevelopmental disorders are caused by genetic or environmental factors that disturb the nervous system’s development during prenatal and early childhood periods. The growing list of genetic mutations that affect mRNA translation raises the question of whether aberrant translatomes in individuals with neurodevelopmental disorders share common molecular features underlying their stereotypical phenotypes and, vice versa, cause a certain degree of phenotypic heterogeneity. Here, we briefly give an overview of the role of local translation during neuronal development. We take the autism‐risk gene list and discuss the molecules that (perhaps) are involved in mRNA transport and translation. Both exaggerated and suppressed translation caused by mutations in those genes have been identified or suggested. Finally, we discuss some proof‐of‐principle regimens for use in autism mouse models to correct dysregulated translation.
Study of open‐type magnetically shielded room for MRI
Authors: Kamata Kiyotaka , Tamari Yozo , Temma Satoru , Goto Koshi , Yunokuchi Kazutomo
Published: November 2018

The magnetic resonance imaging (MRI) is usually installed in a magnetically shielded room (MSR), in order to reduce the leakage flux density to less than 0.5 mT outside the room. The small space enclosed by the wall causes patients a great deal of stress and discomfort because they are isolated from the operators and from the scenery outside. In order to improve amenity for patients in hospitals, open type of MSRs for MRI, which use canceling coils, combined with square cylinders made by magnetic and conductive material, and magnetic material plates instead of magnetic walls. The magnetic shielding effects of open type of MSR combined with square cylinders model made by magnetic, conductive material, magnetic material plates model, and lattice shape model made of magnetic material for MRI are estimated by 3D magnetic field analysis. In this report, we clarify simple lattice of magnetic plate with gap to improve shielding performance using 3D magnetic field analysis.
Observation of tool use in striped skunks: how community science and social media help document rare natural phenomena
Authors: Pesendorfer Mario B. , Dickerson Suzanne , Dragoo Jerry W.
Published: November 2018

Tool use, the manipulation of one object to change the state of another, is found in <1% of animal taxa and most often observed in captivity. Here, we report the observation of tentative tool use in a wild striped skunk (Mephitis mephitis), captured by a trail camera in the front yard of a hobby naturalist who shared the photographs on social media. The skunk is shown manipulating a rock in a manner that strongly suggests the goal of breaking the frozen surface of a water bowl to drink. Skunks join other carnivores that innovated tool use and proto‐tool use in the context of extractive foraging. Their versatile dexterity and manipulative foraging, likely facilitated by their large relative brain size, provide the ideal context for the innovation of novel foraging techniques. We therefore hypothesize that tool use will be observed in other members of the skunk family (Mephitidae), particularly as the broad availability of trail cameras, and the rapid dissemination of interesting observations via social media will increase the discovery rate of rare natural history phenomena. We encourage our colleagues to strengthen this pipeline to discovery, which reverses the information flow of community science projects, to bring amateur and professional naturalists closer together.
Fenced sanctuaries deliver conservation benefits for most common and threatened native island birds in New Zealand
Authors: Bombaci Sara , Pejchar Liba , Innes John
Published: November 2018

Island species are disproportionately threatened with extinction, and invasive species are the primary driver of biodiversity loss. Globally, eradicating invasive mammals from small oceanic islands has led to the recovery of threatened populations, but eradicating mammals from large islands and continents is more challenging. In New Zealand, conservation organizations have established a large network of fenced sanctuaries that use predator‐proof fencing to exclude invasive mammals and conserve native flora and fauna. Yet, critics question if sanctuaries meet these targets, given a lack of evidence on outcomes. We surveyed birds in three sanctuaries and three paired sites on New Zealand's North Island to investigate whether sanctuaries increase bird population densities relative to sites with minimal mammal control. Densities of nine endemic bird species were higher in sanctuaries compared to unprotected sites (0.27–9.00 more birds/ha), but we found no significant difference in mean population densities for introduced and biogeographically recent native species. These findings provide compelling evidence that fenced sanctuaries effectively conserve native island bird populations, and affirm predictions that native species are more likely to benefit from invasive mammal eradications than introduced species. New Zealand's novel approach to recovering rare species holds great promise for conserving biota at risk from invasion in other global hotspots of endemism.
Imprints of management history on hemiboreal forest ecosystems in the Baltic States
Authors: Jõgiste Kalev , Frelich Lee E. , Laarmann Diana , Vodde Floortje , Baders Endijs , Donis Janis , Jansons Aris , Kangur Ahto , Korjus Henn , Köster Kajar , Kusmin Jürgen , Kuuluvainen Timo , Marozas Vitas , Metslaid Marek , Metslaid Sandra , Polyachenko Olga , Poska Anneli , Rebane Sille , Stanturf John A.
Published: November 2018

In the Baltic States region, anthropogenic disturbances at different temporal and spatial scales mostly determine dynamics and development phases of forest ecosystems. We reviewed the state and condition of hemiboreal forests of the Baltic States region and analyzed species composition of recently established and permanent forest (PF). Agricultural deforestation and spontaneous or artificial conversion back to forest is a scenario leading to ecosystems designated as recent forest (RF, age up to two hundred years). Permanent forest (PF) was defined as areas with no records of agricultural activity during the last 200 yr, including mostly forests managed by traditional even‐aged (clear‐cut) silviculture and salvage after natural disturbances. We hypothesized that RF would have distinctive composition, with higher dominance by hardwoods (e.g., aspen and birch), compared to PF. Ordination revealed divergence in the RF stands; about half had the hypothesized composition distinct from PF, with a tight cluster of stands in the part of the ordination space with high hardwood dominance, while the remaining RF stands were scattered throughout the ordination space occupied by PF with highly variable species composition. Planting of conifers, variability in site quality, and variability in spatial proximity to PF with relatively natural ecosystem legacies likely explained the variable compositions of this latter group of RF. We positioned the observations of RF in a classic quantification of site type conditions (based on Estonian forest vegetation survey previously carried out by Lõhmus), which indicated that RF was more likely to occur on areas of higher soil fertility (in ordination space). Climatic and anthropogenic changes to RF create complex dynamic trends that are difficult to project into the future. Further research in tracing land use changes (using pollen analysis and documented evidence) should be utilized to refine the conceptual framework of ecosystem legacy and memory. Occurrence and frequency of deforestation and its characteristics as a novel disturbance regime are of particular interest.
Constituents of effective support for homecare workers providing care to people with dementia at end of life
Authors: Yeh I‐Ling , Samsi Kritika , Vandrevala Tushna , Manthorpe Jill
Published: November 2018

Objective

The aim of this study was to enhance understanding about homecare workers providing care to people with dementia at end of life by exploring homecare workers' perceptions of challenges and the support they needed and sometimes received.

Methods

Qualitative semi‐structured interviews were conducted with 29 homecare workers and 13 homecare managers in England. Framework analysis was used to analyse the data.

Findings

Four overarching challenges were identified: working with clients with dementia, including clients' sometimes unpredictable responses, communication difficulties, and mood changes; caring for the dying; conflict with family members; and working alone, which often left homecare workers at risk of exhaustion, fatigue, and a sense of isolation. When their work entailed high levels of emotion, such as a client's death or getting embroiled in a client's family conflict, they felt emotionally drained, under‐prepared, and overwhelmed. Supportive elements include receiving encouragement and learning from experienced peers and their feelings being acknowledged by managers at their employing homecare agency. Some workers were offered time off or encouraged to attend the client's funeral as a means of supporting the process of bereavement.

Conclusions

Peer and manager support are essential and effective in coping with work pressures. There is a need to develop models of effective support to alleviate staff's practical, emotional, and interpersonal pressures. However, due to the isolating nature of homecare work, managers may not recognise early signs of their staff finding stress unmanageable and miss the opportunity to mitigate these negative effects.
Social decision‐making in the brain: Input‐state‐output modelling reveals patterns of effective connectivity underlying reciprocal choices
Authors: Shaw Daniel , Czekóová Kristína , Gajdoš Martin , Staněk Rostislav , Špalek Jiří , Brázdil Milan
Published: November 2018

During social interactions, decision‐making involves mutual reciprocity—each individual's choices are simultaneously a consequence of, and antecedent to those of their interaction partner. Neuroeconomic research has begun to unveil the brain networks underpinning social decision‐making, but we know little about the patterns of neural connectivity within them that give rise to reciprocal choices. To investigate this, the present study measured the behaviour and brain function of pairs of individuals (N = 66) whilst they played multiple rounds of economic exchange comprising an iterated ultimatum game. During these exchanges, both players could attempt to maximise their overall monetary gain by reciprocating their opponent's prior behaviour—they could promote generosity by rewarding it, and/or discourage unfair play through retaliation. By adapting a model of reciprocity from experimental economics, we show that players' choices on each exchange are captured accurately by estimating their expected utility (EU) as a reciprocal reaction to their opponent's prior behaviour. We then demonstrate neural responses that map onto these reciprocal choices in two brain regions implicated in social decision‐making: right anterior insula (AI) and anterior/anterior‐mid cingulate cortex (aMCC). Finally, with behavioural Dynamic Causal Modelling, we identified player‐specific patterns of effective connectivity between these brain regions with which we estimated each player's choices with over 70% accuracy; namely, bidirectional connections between AI and aMCC that are modulated differentially by estimates of EU from our reciprocity model. This input‐state‐output modelling procedure therefore reveals systematic brain–behaviour relationships associated with the reciprocal choices characterising interactive social decision‐making.
Machine learning of brain gray matter differentiates sex in a large forensic sample
Authors: Anderson Nathaniel E. , Harenski Keith A. , Harenski Carla L. , Koenigs Michael R. , Decety Jean , Calhoun Vince D. , Kiehl Kent A.
Published: November 2018

Differences between males and females have been extensively documented in biological, psychological, and behavioral domains. Among these, sex differences in the rate and typology of antisocial behavior remains one of the most conspicuous and enduring patterns among humans. However, the nature and extent of sexual dimorphism in the brain among antisocial populations remains mostly unexplored. Here, we seek to understand sex differences in brain structure between incarcerated males and females in a large sample (n = 1,300) using machine learning. We apply source‐based morphometry, a contemporary multivariate approach for quantifying gray matter measured with magnetic resonance imaging, and carry these parcellations forward using machine learning to classify sex. Models using components of brain gray matter volume and concentration were able to differentiate between males and females with greater than 93% generalizable accuracy. Highly differentiated components include orbitofrontal and frontopolar regions, proportionally larger in females, and anterior medial temporal regions proportionally larger in males. We also provide a complimentary analysis of a nonforensic healthy control sample and replicate our 93% sex discrimination. These findings demonstrate that the brains of males and females are highly distinguishable. Understanding sex differences in the brain has implications for elucidating variability in the incidence and progression of disease, psychopathology, and differences in psychological traits and behavior. The reliability of these differences confirms the importance of sex as a moderator of individual differences in brain structure and suggests future research should consider sex specific models.
Hepatitis B Treatment: What We Know Now and What Remains to Be Researched
Authors: Suk‐Fong Lok Anna
Published: November 2018

Chronic hepatitis B virus (HBV) infection remains a major global health burden. Currently, two types of treatment, interferons (IFNs) and nucleos(t)ide analogues (NAs), have been approved. These treatments are effective in suppressing HBV replication and in decreasing the risk of developing cirrhosis, liver failure, hepatocellular carcinoma (HCC), and death. However, these treatments do not eliminate the virus, and the risk of HCC remains. This review article summarizes current knowledge about the safety, efficacy, and clinical indications of hepatitis B treatment. It also discusses limitations of existing treatment, gaps in knowledge, and feasibility of a hepatitis B cure.
Progression‐free survival and one‐year milestone survival as surrogates for overall survival in previously treated advanced non‐small cell lung cancer
Authors: Zhao Shen , Zhang Zhonghan , Zhang Yaxiong , Hong Shaodong , Zhou Ting , Yang Yunpeng , Fang Wenfeng , Zhao Hongyun , Zhang Li
Published: November 2018

The advent of immunotherapy leads to greater availability of effective subsequent treatments and extended survival in previously treated advanced non‐small cell lung cancer (NSCLC), complicating the evaluation of overall survival (OS) in second‐line NSCLC trials. Here, we aimed to assess the surrogacy of progression‐free survival (PFS) and milestone survival for OS in second‐line NSCLC trials investigating chemotherapy, targeted therapy and immunotherapy, respectively. We systemically searched for active‐controlled, second‐line NSCLC trials. The milestone time point was set at one‐year based on pre‐analysis. A two‐stage meta‐analytic validation model was adopted to assess associations between surrogate endpoint (SE) and OS and associations between treatment effects on SE and OS. Treatment effects on SE and OS were expressed as PFS hazard ratios (HRPFS), 1 yr‐milestone ratio (Ratio1y‐SUR) and HROS. Subgroup analyses stratified by treatment types and trial publication years evaluated the surrogacy in different clinical contexts. The study included 50 trials with 22,804 patients. One‐year survival strongly correlated with OS (R2[95% confidence interval]: one‐year survival ‐median OS = 0.707 [0.704–0.708]; Ratio1y‐SUR‐HROS = 0.829 [0.828–0.831]). No correlation was established between PFS and OS (median PFS‐median OS = 0.100 [0.098–0.101]; HRPFS‐HROS = 0.064 [0.059–0.069]), except in immunotherapy subgroup (HRPFS‐HROS = 0.835 [0.791–0.918]). In subgroup analyses, surrogacy of one‐year survival persisted in different clinical contexts, and the disassociation between PFS and OS persisted in recent trials. One‐year milestone survival showed strong surrogacy for OS in second‐line NSCLC trials. Although no association was identified between PFS and OS, the strong HRPFS‐HROS correlation in immunotherapy trials indicates the potential of PFS as a SE in NSCLC trials involving immunotherapies.
Informing the Delineation of Input Uncertainty Space in Exploratory Modelling Using a Heuristic Approach
Authors: Moallemi Enayat A. , Elsawah Sondoss , Ryan Michael J.
Published: November 2018

Exploratory modelling is an emerging approach which can address the challenge of model‐based decision making in dealing with input model uncertainties. Exploratory modelling samples from an input uncertainty space and generates extensive computational experiments to analyse possible model behaviours in an output solution space. The way that the input uncertainty space is delineated influences the results of exploratory modelling and its computational cost. In this article, we show the statistical significance of the implication of the size of an input uncertainty space on the resulted output solution space. We also propose a heuristic approach which informs the delineation of input uncertainties by screening the relevant model behaviour in the solution space. An illustrative example of an aircraft fleet management system is used to demonstrate the implementation of our approach in practice. We conclude that the delineation of input uncertainty space can be a way to control simulations in exploratory modelling and to enhance the efficiency of the exploration process and the confidence of the final results.
Envisioning Systems Engineering as a Transdisciplinary Venture
Authors: Sillitto Hillary , Martin James , Griego Regina , McKinney Dorothy , Arnold Eileen , Godfrey Patrick , Dori Dov , Krob Daniel , Jackson Scott
Published: November 2018

We envision that systems engineering can be transformed into a truly transdisciplinary discipline ‐ a foundational meta‐discipline that supports and enables collaboration between all the disciplines that should be involved in conceiving, building, using and evolving a system such that it will continue to be successful and fit for purpose as time passes. Systems engineering can be applied in different ways depending on the situation and how well current systems engineering process patterns are matched to the problem in hand. We identify four elements of this new transdisciplinary framework: systems engineering tenets; systems engineering approach; systems engineering process; and systems engineering toolbox. We suggest that the use of systems engineering then needs to be considered in three domains: problem space, solution space, and transformation space that helps us along the development‐delivery‐evolution trajectory. We propose twelve systems engineering tenets and show how they should be applied in these three domains. We perceive that even though all elements of the current systems engineering process can be justified in terms of the twelve tenets applied to these three domains, the current commonly used, standardized systems engineering process is not suitable for all situations requiring a systems engineering approach or an application of the systems engineering tenets. We claim that the framework presented in this paper can act as a unifying structure that facilitates the evolution of systems engineering from the current focus on a “standardized” process model suited to a particular class of problem, to a more agile and capable “transdiscipline” that will provide an enabling construct for more successful collaborations that can better deal with a wider range of complicated, complex and chaotic problem situations.
A Framework for Testability Analysis from a Systems Architecture Perspective
Authors: Efatmaneshnik Mahmoud , Ryan Michael J , Shoval Shraga
Published: November 2018

In this paper, we study the effects of system architecture on testability. We present a probabilistic model of testability that enables us to study the relationships between system architecture and testability. A Markov Chain model obtains the quality of system after test as a function of its quality before test and the test quality. We focus on the costs and benefits associated with the modularization for testability. We show that choosing the proper testing architecture through careful modularization can enhance efficiency and effectiveness of system testing. We base the model on repetitive testing which means we will repeat the test after a fail test outcome.
Perspectives on Managing Emergent Risk Due to Rising Complexity in Aerospace Systems
Authors: DeTurris Dianne , Palmer Andrew
Published: November 2018

Managing complexity in the aerospace industry is essential for effective development of modern engineered systems. Preventing emergent risk while maintaining cost and schedule discipline is the main objective for addressing uncontrolled self‐organization due to complexity. Engineers can quantify emergent risk by viewing systems from multiple stakeholder and design perspectives to assess unforeseen behaviors more accurately. In aerospace engineers consider and transpose methods for dealing with complexity that come from the systems, organizational, and complexity science perspectives. This survey highlights commonalities between complexity management methods, systems design models, and elements of systems thinking that can help engineers predict and prepare for emergent behavior in the system. Using new points‐of‐view in design gives practicing engineers more information with which to view and manipulate system properties. The solution for managing complexity lies in multidisciplinary collaboration to solve problems that span multiple academic domains.
Adaptive Cyber‐Physical‐Human Systems: Exploiting Cognitive Modeling and Machine Learning in the Control Loop
Authors: Madni Azad M. , Sievers Michael , Madni Carla Conaway
Published: November 2018

Cyber‐physical‐human (CPH) systems are purposeful arrangements of sensors, computers, communication devices, and humans to perform tasks that achieve specific mission objectives. These systems typically allow other systems, devices, and data streams to connect/disconnect as needed during mission execution. The roles of humans in CPH systems are quite varied. In adaptive CPH systems, humans collaborate with the cyber‐physical elements to jointly accomplish tasks, and adapt to changing contexts to accomplish mission goals. Mutual adaptation based on prior knowledge, cognitive modeling, and online machine learning are key characteristics of adaptive CPH systems. This paper presents key challenges in realizing adaptive CPH systems. It discusses learning and adaptation, as well as human and CPS roles in adaptive CPH systems. It offers a functional (reference) architecture to inform and guide the development of adaptive CPH systems. It concludes with a discussion of research needed to advance the state‐of‐the‐art of adaptive CPH systems.
Rethinking Bone Disease in Kidney Disease
Authors: Damasiewicz Matthew J , Nickolas Thomas L
Published: November 2018

Renal osteodystrophy (ROD) is the bone component of chronic kidney disease mineral and bone disorder (CKD‐MBD). ROD affects bone quality and strength through the numerous hormonal and metabolic disturbances that occur in patients with kidney disease. Collectively these disorders in bone quality increase fracture risk in CKD patients compared with the general population. Fractures are a serious complication of kidney disease and are associated with higher morbidity and mortality compared with the general population. Furthermore, at a population level, fractures are at historically high levels in patients with end‐stage kidney disease (ESKD), whereas in contrast the general population has experienced a steady decline in fracture incidence rates. Based on these findings, it is clear that a paradigm shift is needed in our approach to diagnosing and managing ROD. In clinical practice, our ability to diagnose ROD and initiate antifracture treatments is impeded by the lack of accurate noninvasive methods that identify ROD type. The past decade has seen advances in the noninvasive measurement of bone quality and strength that have been studied in kidney disease patients. Below we review the current literature pertaining to the epidemiology, pathology, diagnosis, and management of ROD. We aim to highlight the pressing need for a greater awareness of this condition and the need for the implementation of strategies that prevent fractures in kidney disease patients. Research is needed for more accurate noninvasive assessment of ROD type, clinical studies of existing osteoporosis therapies in patients across the spectrum of kidney disease, and the development of CKD‐specific treatments. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
LncRNA CRNDE promotes the epithelial‐mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/β‐catenin signaling pathway
Authors: Zhu Liying , Yang Nenghong , Du Guiqin , Li Chengcheng , Liu Guoqi , Liu Shengju , Xu Yongjie , Di Yanan , Pan Wei , Li Xing
Published: November 2018

Colorectal neoplasia differentially expressed (CRNDE) is a significantly upregulated long noncoding RNA in hepatocellular carcinoma (HCC). CRNDE could promote cell proliferation, migration, and invasion, while its molecular mechanisms were still largely unclear. In this study, we investigated the expression and function of CRNDE. CRNDE was significantly upregulated in tumor tissues compared with adjacent normal tissues. In vitro, we revealed that knockdown of CRNDE inhibited cell proliferation, migration, and cell invasion capacities in HCC. Animal studies indicated that CRNDE knockdown represses both growth and metastasis of HCC tumors in vivo. Moreover, knockdown of CRNDE suppressed the cell epithelial‐mesenchymal transition (EMT) process by increasing the expression of E‐cadherin and ZO‐1, whereas, decreasing the expression of N‐cadherin, slug, twist, and vimentin in HCC cells. We also revealed that knockdown of CRNDE suppressed the Wnt/β‐catenin signaling in HCC. Thus, CRNDE could modulate EMT of HCC cells and knockdown of CRNDE impaired the mesenchymal properties. CRNDE increased invasion of HCC cells might be through activating the Wnt/β‐catenin signaling pathway.
Traditional Chinese medicine as targeted treatment for epithelial‐mesenchymal transition‐induced cancer progression
Authors: Liu Jianrong , Ke Fei , Cheng Haibo , Zhou Jinrong
Published: November 2018

The epithelial‐mesenchymal transition (EMT) program, which loosens cell‐cell adhesion complexes, endows cells with enhanced migratory and invasive properties. Furthermore, this process facilitates both the development of drug resistance and immunosuppression by tumor cells, which preclude the successful treatment of cancer. Recent research has demonstrated that many signaling pathways are involved in EMT progression. In addition, cancer stem cells (CSCs), vasculogenic mimicry (VM) and the tumor‐related immune microenvironment all play important roles in tumor formation. However, there are few reports on the relationships between EMT and these factors. In addition, in recent years, traditional Chinese medicine (TCM) has developed a unique system for treating cancer. In this review, we summarize the crucial signaling pathways associated with the EMT process in cancer patients and discuss the interconnections between EMT and other molecular factors (such as CSCs, VM, and the tumor‐related immune microenvironment). We attempt to identify common regulators that might be potential therapeutic targets to thereby optimize tumor treatment. In addition, we outline recent research on TCM approaches that target EMT and thereby provide a foundation for further research on the exact mechanisms by which TCMs affect EMT in cancer.
Identification of key lncRNAs in the carcinogenesis and progression of colon adenocarcinoma by co‐expression network analysis
Authors: Jiang Shi , Tan Biyong , Zhang Xingqiang
Published: November 2018

Colon adenocarcinoma (COAD) is one of the most common cancers, and its carcinogenesis and progression is influenced by multiple long non‐coding RNAs (lncRNA), especially through the miRNA sponge effect. In this study, more than 4000 lncRNAs were re‐annotated from the microarray datasets through probe sequence mapping to obtain reliable lncRNA expression profiles. As a systems biology method for describing the correlation patterns among genes across microarray samples, weighted gene co‐expression network analysis was conducted to identify lncRNA modules associated with the five stepwise stages from normal colonic samples to COAD (n = 94). In the most relevant module (R2 = −0.78, P = 4E‐20), four hub lncRNAs were identified (CTD‐2396E7.11, PCGF5, RP11‐33O4.1, and RP11‐164P12.5). Then, these four hub lncRNAs were validated using two other independent datasets including GSE20916 (n = 145) and GSE39582 (n = 552). The results indicated that all hub lncRNAs were significantly negatively correlated with the three‐stage colonic carcinogenesis, as well as TNM stages in COAD (one‐way analysis of variance P < 0.05). Kaplan‐Meier survival curve showed that patients with higher expression of each hub lncRNA had a significantly higher overall survival rate and lower relapse risk (log‐rank P < 0.05). In conclusion, through co‐expression analysis, we identified and validated four key lncRNAs in association with the carcinogenesis and progression of COAD, and these lncRNAs might have important clinical implications for improving the risk stratification, therapeutic decision and prognosis prediction in COAD patients.
Synthesis, characterization, and catalytic application of Fe3O4‐Si‐[CH2]3‐N=CH‐aryl for the efficient synthesis of novel poly‐substituted pyridines
Authors: Ashouri Mojtaba , Kefayati Hassan , Shariati Shahab
Published: November 2018

Fe3O4 magnetic nanoparticles (MNPs) were functionalized by aminopropylsilane and reacted with aromatic aldehyde, and Fe3O4‐Si‐[CH2]3‐N=CH‐Aryl and Fe3O4‐Si‐(CH2)3‐NH‐CH2‐Aryl MNPs were prepared as novel magnetic nanocatalysts. Fourier transform infrared (FT‐IR), X‐ray diffraction (XRD), and scanning and transmission electron microscopy (SEM and TEM) were used to identify the MNPs. The catalytic activity of the MNPs was evaluated in the one‐pot synthesis of some novel poly‐substituted pyridine derivatives.
The Alliance and Rupture Observation Scale (AROS): Development and validation of an alliance and rupture measure for repeated observations within psychotherapy sessions
Authors: Larsson Mattias Holmqvist , Björkman Karin , Nilsson Karin , Falkenström Fredrik , Holmqvist Rolf
Published: November 2018

Objective

The aim of this study was to test a new observer‐rated instrument, the Alliance and Rupture Observation Scale (AROS). It was designed for repeated measurements of the alliance within sessions and to detect alliance ruptures.

Method

Videotaped therapy sessions with depressed adults were analyzed. Reliability was mainly assessed as inter‐rater reliability. Convergent, predictive, and discriminant validity of the AROS was assessed by comparing the instrument with both observer‐rated and patient‐rated measures.

Results

The AROS exhibited excellent inter‐rater reliability. Alliance levels measured with the AROS predicted patients’ ratings of the alliance in the same session and were highly correlated with another observer‐rated alliance measure. Alliance patterns (rupture; repair; and no‐rupture) based on AROS scores were significantly correlated with patients’ ratings of the alliance.

Conclusions

Preliminary support for convergent and predictive validity was found. It is yet to be determined whether AROS scores are related to psychotherapy outcomes.
A qualitative analysis of emotion and emotion regulation in hoarding disorder
Authors: Taylor Jasmine K. , Theiler Stephen , Nedeljkovic Maja , Moulding Richard
Published: November 2018

Objective

The role of emotion regulation (ER) has been receiving increased attention in relation to various forms of psychopathology including hoarding disorder (HD). However, questionnaire designs are limited to finding associations of ER with symptoms or symptom groups, without finding out how such constructs might be involved in the disorder.

Methods

This study was a qualitative investigation of ER in a clinical HD sample (N = 11).

Results

Prominent themes provided support for ER difficulties in hoarding. In particular, difficulties with identifying and describing feelings, unhelpful attitudes toward the emotional experience, the use of avoidance‐based strategies, and a perceived lack of effective ER strategies were prominent themes. Furthermore, emotional factors were identified as being associated with the onset and/or exacerbation of hoarding behavior, and possessions and acquiring behavior appeared to serve an ER function.

Conclusion

The current paper provides a nuanced account of the role of ER in hoarding difficulties.
High‐speed quantitative 3D imaging by dual‐illumination holographic microscopy
Authors: Donnarumma Dario , Rawat Nitin , Brodoline Alexey
Published: November 2018

A new blood flow imaging (BFI) technique using digital holography with double illumination of the sample is proposed. We imaged the moving red blood cells (RBCs) using a two microscope objective lenses setup. The setup consists in a larger angle of separation (90 °) between the two illumination beams, allowing a wider angular rotation at good z resolution. Moreover, the setup geometry allows an easier displacement of the sample in all directions. Results show that this technique is able to perform phase‐shifting reconstruction for the two beams at the same time which is more suitable for the future implementation of live 3D holography. Experimental results are carried out for the verification of the effectiveness of the proposed technique on a zebrafish larvae sample.

Research highlights

Blood flow imaging techniques are often invasive and image analysis is time consuming.

To alleviate this issue an imaging technique based on dual illumination in holographic domain is proposed.

This method has been validated on zebrafish embryos.
A Triple‐Classification Radiomics Model for the Differentiation of Primary Chordoma, Giant Cell Tumor, and Metastatic Tumor of Sacrum Based on T2‐Weighted and Contrast‐Enhanced T1‐Weighted MRI
Authors: Yin Ping , Mao Ning , Zhao Chao , Wu Jiangfen , Chen Lei , Hong Nan
Published: November 2018

Background

Preoperative differentiation between primary sacral chordoma (SC), sacral giant cell tumor (SGCT), and sacral metastatic tumor (SMT) is important for treatment decisions.

Purpose

To develop and validate a triple‐classification radiomics model for the preoperative differentiation of SC, SGCT, and SMT based on T2‐weighted fat saturation (T2w FS) and contrast‐enhanced T1‐weighted (CE T1w) MRI.

Study type

Retrospective.

Population

A total of 120 pathologically confirmed sacral patients (54 SCs, 30 SGCTs, and 36 SMTs) were retrospectively analyzed and divided into a training set (n = 83) and a validation set (n = 37).

Field strength/sequence

The 3.0T axial T2w FS and CE T1w MRI.

Assessment

Morphology, intensity, and texture features were assessed based on Formfactor, Haralick, Gray‐level co‐occurrence matrix (GLCM), Gray‐level run‐length matrix (GLRLM), histogram.

Statistical tests

Analysis of variance, least absolute shrinkage and selection operator (LASSO), Pearson correlation, Random Forest (RF), area under the receiver operating characteristic curve (AUC) and accuracy analysis.

Results

The median age of SGCT (33.5, 25.3–45.5) was significantly lower than those of SC (58.0, 48.8–64.3) and SMT (59.0, 46.3–65.5) groups (χ2 = 37.6; P < 0.05). No significant difference was found when compared in terms of genders, tumor locations, and tumor sizes of SC, SGCT, and SMT (; P1 = 0.15, P2 = 0.29, P3 = 0.06). For the differential value, features extracted from joint T2w FS and CE T1w images outperformed those from T2w FS or CE T1w images alone. Compared with CE T1w images, features derived from T2w FS images yielded higher AUC in both training and validating set. The best performance of radiomics model based on joint T2w FS and CE T1w images reached an AUC of 0.773, an accuracy of 0.711.

Data conclusion

Our 3.0T MRI‐based triple‐classification radiomics model is feasible to differentiate SC, SGCT, and SMT, which may be applied to improve the precision of preoperative diagnosis in clinical practice.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:752–759.
Characterization of clinical human prostate cancer lesions using 3.0‐T sodium MRI registered to Gleason‐graded whole‐mount histopathology
Authors: Broeke Nolan C. , Peterson Justin , Lee Joseph , Martin Peter R. , Farag Adam , Gomez Jose A. , Moussa Madeleine , Gaed Mena , Chin Joseph , Pautler Stephen E. , Ward Aaron , Bauman Glenn , Bartha Robert , Scholl Timothy J.
Published: November 2018

Background

Overtreatment of prostate cancer (PCa) is a healthcare issue. Development of noninvasive imaging tools for improved characterization of prostate lesions might reduce overtreatment.

Purpose

To measure the distribution of tissue sodium concentration (TSC), proton T2‐weighted signal, and apparent diffusion coefficient (ADC) values in human PCa and to test the presence of a correlation between regional differences in imaging metrics and the Gleason grade of lesions determined from histopathology.

Study Type

Cross‐sectional.

Subjects

Ten men with biopsy‐proven PCa.

Sequences/Field Strength

Sodium, proton T2‐weighted, and diffusion‐weighted MRI data were acquired using Broad‐Band 3D‐Fast‐Gradient‐Recalled, 3D Cube (Isotropic 3D‐Fast‐Turbo‐Spin‐Echo acquisition) and 2D Spin‐Echo sequences, respectively, with a 3.0T MR scanner.

Assessment

All imaging data were coregistered to Gleason‐graded postprostatectomy histology, as the standard for prostate cancer lesion characterization. Regional TSC and T2 data were assessed using percent changes from healthy tissue of the same patient (denoted ΔTSC, ΔT2).

Statistics

Differences in ΔTSC, ADC, and ΔT2 as a function of Gleason score were analyzed for each imaging contrast using a one‐way analysis of variance or a nonparametric t‐test. Correlations between imaging data measures and Gleason score were assessed using a Spearman's ranked correlation.

Results

Evaluation of the correlation of ΔTSC, ADC, and ΔT2 datasets with Gleason scoring revealed that only the correlation between ΔTSC and Gleason score was statistically significant (rs = 0.791, p < 0.01), whereas the correlations of ADC and ΔT2 with Gleason score were not (rs = –0.306, p = 0.079 and r
s = –0.069, p = 0.699, respectively). In addition, all individual patients showed monotonically increasing ΔTSC with Gleason score.

Data Conclusion

The results of this preliminary study suggest that changes in TSC, assessed by sodium MRI, has utility as a noninvasive imaging assay to accurately characterize PCa lesions. Sodium MRI may provide useful complementary information on mpMRI, which may assist the decision‐making of men choosing either active surveillance or treatment.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:1409–1419.
Amide proton transfer imaging to evaluate the grading of squamous cell carcinoma of the cervix: A comparative study using 18F FDG PET
Authors: Li Beibei , Sun Hongzan , Zhang Siyu , Wang Xiaoqi , Guo Qiyong
Published: November 2018

Background

Amide proton transfer (APT) imaging has shown great potential value in the diagnosis of cancer, but has yet not been applied in cervical carcinoma patients.

Purpose

To investigate the utility of APT imaging in estimating histologic grades of squamous cell carcinoma of the cervix (SCCC), compared with the standardized uptake value (SUV).

Study Type

Prospective.

Population

Thirty‐one patients with SCCC (median age 51 years) were included.

Field Strength/Sequence

Ingenia 3.0 T CX, Axial T1‐weighted imaging (T1WI), Axial T2WI, 3D turbo spin echo sequence for APT imaging.

Assessment

Patient pathology was confirmed by surgery and the patients were divided into three groups based on histologic grades: Grade 1 (n = 9), Grade 2 (n = 12), and Grade 3 (n = 10). The APT signal intensity (APT SI), maximum SUV (SUVmax) and mean SUV (SUVmean) for each grade were assessed by experienced radiologists in a blinded manner.

Statistical Tests

The obtained parameters were compared by one‐way analysis of variance with Tukey honest significant difference post‐hoc test. The correlations between the parameters and histologic grades were analyzed by Spearman's correlation coefficient. The Pearson correlation coefficients of the APT SI with the SUVmax and SUVmean were also calculated.

Results

The APT SIs for the three grades were significantly different (P = 0.0002). The APT SIs of Grade 2 and Grade 3 had significant differences (P = 0.009). The Spearman correlation coefficients for the correlations between the parameters and histological grade were as follows: APT SI: 0.684 (P = 0.00002), SUVmax: 0.318 (P = 0.082), and SUVmean: 0.261 (P = 0.157). The Pearson correlation coefficients of the APT SI with the SUVmax and SUVmean were 0.108 (P = 0.564) and 0.178 (P = 0.337), respectively.

Data Conclusion

The APT SI was positively correlated with the SCCC grades. APT imaging maybe a promising method for predicting SCCC histologic grades.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:261–268.
Duration of postoperative immobilization affects MMP activity at the healing graft–bone interface: Evaluation in a mouse ACL reconstruction model
Authors: Nakagawa Yusuke , Lebaschi Amir H. , Wada Susumu , Green Samuel J. E. , Wang Dean , Album Zoe M. , Carballo Camilla B. , Deng Xiang‐Hua , Rodeo Scott A.
Published: November 2018

Excessive MMP activity may impair tendon‐to‐bone healing. However, little is known about the effect of joint motion on MMP activity after ACL reconstruction. The aim of this study was to determine the effect of different durations of knee immobilization on MMP activity in a mouse ACL reconstruction model using a fluorescent MMP probe which detects MMP 2, 3, 9, and 13 and near‐infra red in vivo imaging. Sixty C57BL male mice underwent ACL reconstruction. Post‐operatively, the animals were treated with free cage activity (Group 1), or with the use of an external fixator to restrict knee motion and weight bearing for 5 days (Group 2), 14 days (Group 3), and 28 days (Group 4). At days 3, 7, 16, 23, and 30, five mice underwent IVIS imaging. At days 3, 7, 16, and 30, histological analysis was also performed. Probe signal intensity in the whole limb peaked at day 7, followed by a decrease at day 16, and maintenance up to day 30. There was no significant difference among groups at any time point based on IVIS, but histologic localization of MMP probe signal showed significantly less activity in Group 2 and Group 3 compared to Group 4 in the bone tunnel at day 30. We demonstrated that short‐term immobilization led to less MMP activity around the bone tunnel compared with prolonged immobilization. A short period of immobilization after ACL reconstruction might enhance graft–bone interface healing by mitigating excess MMP expression. These findings have implications for post‐operative rehabilitation protocols following ACL reconstruction. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:325–334, 2019.