bluuebunny/crossref_metadata_2025 huggingface dataset:
Is chronic ankle instability associated with impaired muscle strength? Ankle, knee and hip muscle strength in individuals with chronic ankle instability: a systematic review with meta-analysis
Authors: Khalaj Nafiseh , Vicenzino Bill , Heales Luke James , Smith Michelle D
Published: January 2020

Objective

Determine whether impairments in lower limb muscle strength exist in individuals with chronic ankle instability (CAI) compared with uninjured controls.

Design

Systematic review with meta-analysis.

Data source

A comprehensive search of PubMed, Cochrane, CINAHL, Web of Science and EMBASE electronic databases from inception to 10 February 2019.

Eligibility criteria for selecting studies

Cross-sectional and case–control studies were included if they objectively measured lower limb muscle strength in individuals with CAI compared with controls. Risk of bias and quality of included studies were assessed. Data of included studies were extracted, and meta-analysis was conducted where appropriate.

Results

12 397 unique studies were identified, of which 20 were included and 16 were eligible for meta-analysis. Reviewed studies clearly described the aim/hypothesis and main outcome measure, but most lacked sample size calculation and assessor blinding. Meta-analyses showed individuals with CAI had lower eccentric and concentric evertor strength (30 and 120°/s; Nm; standardised mean difference (SMD) between −0.73 and −0.95), eccentric invertor strength (60 and 120°/s; both Nm and Nm/kg; SMD between −0.61 and −1.37), concentric invertor strength (60 and 120°/s; Nm; SMD=−0.7) and concentric knee extensor strength (SMD=−0.64) compared with control participants. Ankle eccentric dorsiflexor strength was not different between groups. Although pooling was not possible, data from three separate studies indicated that hip flexor, abductor and external rotator strength, but not hip adductor and extensor strength, was lower in individuals with CAI than in control participants.

Conclusion

Individuals with CAI have ankle inversion and eversion strength deficits. Our data also point to differences between individuals with CAI and controls in hip and knee strength. These elements of the kinetic chain should be evaluated by clinicians who rehabilitate individuals with CAI.

PROSPERO registration number

CRD42016037759.
Metabolic characteristics of Africans with normal glucose tolerance and elevated 1-hour glucose: insight from the Africans in America study
Authors: Briker Sara M , Hormenu Thomas , DuBose Christopher W , Mabundo Lilian S , Chung Stephanie T , Ha Joon , Sherman Arthur , Tulloch-Reid Marshall K , Bergman Michael , Sumner Anne E
Published: January 2020

Introduction

Risk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown.

Objective

We performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L.

Methods

Glucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic.

Results

One-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628).

Conclusions

Although dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.
Web-based decision-making tool for smoking cessation (Pare de fumar conosco) among patients with chronic conditions in Brazil : one-arm feasibility study
Authors: Cupertino Ana Paula , Cartujano-Barrera Francisco , Basile Colugnati Fernando Antonio , Batista Formagini Taynara Dutra , Garcia de Siqueira Galil Arise , Ferreira Carvalho Banhato Eliane , Ferreira Marilda Aparecida , Richter Kimber P
Published: January 2020

Objective

To assess the feasibility of Pare de fumar conosco, a web-based smoking cessation decision-making tool, among patients with chronic conditions in Brazil.

Methods

We recruited 85 Brazilian smokers in two clinical centres for chronic conditions to complete Pare de fumar conosco. Outcome measures included interest in using smoking cessation resources and self-reported 7-day point prevalence abstinence 12 weeks following the intervention.

Results

The average age of participants was 54.2 years old (SD=10.5) and 77.9% had not completed high school. All participants were daily smokers and the majority smoked ≥11 cigarettes per day (63.5%). Pre–post intervention interest in using pharmacotherapy and group counselling significantly increased (82.4% vs 22.4%, p≤0.0001; and 85.9% vs 21.2%, p≤0.0001, respectively). At 12 weeks, eight participants (9.4%) reported 7-day point prevalence abstinence using intention-to-treat analysis (35.2% follow-up rate).

Conclusion

The Pare de fumar conosco smoking cessation web-based tool significantly increased interest in pharmacotherapy and behavioural counselling. Additional testing as a formal randomised clinical trial appears warranted.
Molecular characterisation of oncogenic urothelial mosaic mutations in patients with extensive keratinocytic epidermal naevi
Authors: Gadea Alejandra , Hernández-Muñoz Inmaculada , Vicente Asunción , Andrades Evelyn , García-Calvente Miriam , Camacho Laura , Fernandez-Rodríguez Conchi , Bellosillo Beatriz , Pujol Ramon , Toll Agustín
Published: January 2020

Background: Keratinocytic epidermal naevi (KENs) are congenital benign skin mosaic lesions that share common mutations with some subsets of urothelial carcinomas. Moreover, several patients with extensive KEN who also developed urothelial carcinomas at young ages have been reported. Thus, patients with extensive KEN may harbour mosaic urothelial oncogenic mutations that would favour the early development of urothelial carcinomas. Methods: We selected five patients with extensive KEN involving the lower part of the back and performed a molecular characterisation of urothelial and cutaneous samples using a next-generation sequencing (NGS) custom panel targeting candidate oncogenic genes. Results: Mosaic pathogenic mutations were detected in KEN in all patients. In four out of five patients, mosaic pathogenic mutations in FGFR2 or HRAS were also detected in samples from the urothelial tract. Moreover, we report a patient who developed urothelial carcinomas at age 29 and harboured an HRAS G12S mutation both in skin and urothelial tumour samples. Conclusions: We conclude that patients with extensive KEN involving the lower part of the back frequently harbour oncogenic mutations in the urothelium that may induce the development of carcinomas. NGS panels can be considered as highly sensitive tools to identify this subgroup of patients, which might permit adoption of screening measures to detect malignant transformation at early stages.
Use of four‐layer porcine small intestinal submucosa alone as a scaffold for the treatment of deep corneal defects in dogs and cats: preliminary results
Authors: Barachetti Laura , Zanni Marco , Stefanello Damiano , Rampazzo Antonella
Published: January 2020

Background

To describe the efficacy of four‐layer porcine small intestinal submucosa (Vetrix BioSIS plus+) as single scaffold for the treatment of deep corneal lesions in dogs and cats.

Methods

10 dogs and 3 cats with deep or full thickness corneal defects were treated surgically with BioSIS plus graft. Corneal transparency scores and vision were evaluated.

Results

Lesions in dogs were four perforations, three descemetoceles, two limbal melanocytomas and one deep corneal ulcer. In cats, there were one limbal melanocytoma and two perforations. The average length of the follow‐up was 86 days. In all, 12 out of 13 eyes treated were visual at last recheck (92.3 per cent). The scars were mild eight cases (66.7 per cent), but denser in four cases (33.4 per cent). Complication were partial collagenolysis in three cases (25 per cent), which resolved with medical therapy, mild corneal pigmentation in one case (8.4 per cent) and anterior synechia in one case (8.4 per cent). One case experienced severe collagenolysis and was enucleated 21 days postoperatively.

Conclusions

Four‐layer porcine SIS graft was successfully used for surgical treatment of deep corneal lesions in selected corneal diseases in a small series of dogs and cats, with good results in terms of mechanic support and corneal transparency.
Laboratory-scale pull-out tests on a geothermal energy pile in dry sand subjected to heating cycles
Authors: Elzeiny Rehab , Suleiman Muhannad T. , Xiao Suguang , Qamar Mu’ath Abu , Al-Khawaja Mohammed
Published: January 2020

Ground source heat pumps coupled with energy piles operate intermittently, subjecting the piles to temperature cycles throughout their lifetime. The research presented in this paper focuses on studying the thermomechanical behavior of energy piles subjected to heating cycles. Laboratory model tests were performed at the soil-structure interaction (SSI) facility at Lehigh University. A fully instrumented model energy pile, embedded in dry sand, was subjected to different number of heating cycles followed by axial pull-out loading. Baseline (room temperature), five heating cycles (5HC), and 100 heating cycles (100HC) tests are reported in this paper. The soil was instrumented with temperature sensors and pressure sensors, while the pile was instrumented with temperature sensors, strain gauges, and pressure sensors. The test results showed that the peak pull-out loads for the baseline, 5HC, and 100HC were 2794 N, 3633 N (30% higher than baseline), and 3559 N (27% higher than baseline), respectively. It was also found that subjecting the pile to large number of daily heating cycles induced small degradation in the load transfer or the peak pull-out load in dry sand.
Complex network structure extraction based on community relevance
Authors: Ding Jingyi , Jiao Licheng , Wu Jianshe , Liu Fang
Published: January 2020

One way to understand the network function and analyze the network structure is to find the communities of the network accurately. Now, there are many works about designing algorithms for community detection. Most community detection algorithms are based on modularity optimization. However, these methods not only have disadvantages in computational complexity, but also have the problem of resolution restriction. Designing a community detection algorithm that is fast and effective remains a challenge in the field. We attempt to solve the community detection problem in a new perspective in this paper, believing that the assumption used to solve the link prediction problem is useful for the problem of community detection. By using the similarity between modules of the network, we propose a new method to extract the community structure in this paper. Our algorithm consists of three steps. First, we initialize a community partition based on the distribution of the node degree; second, we calculate the similarity between different communities, where the similarity is the index to describe the closeness of the different communities. We assume that the much closer the two different communities are, the greater the likelihood of being divided together; finally, merge the pairs of communities which has the highest similarity value as possible as we can and stop when the condition is not satisfied. Because the convergence of our algorithm is very fast in the process of merging, we find that our method has advantages both in the computational complexity and in the accuracy when compared with other six classical algorithms. Moreover, we design a new measure to describe how difficulty the network division is.
Coherent optical transition radiation imaging for compact accelerator electron-beam diagnostics
Authors: Lumpkin A. H.
Published: January 2020

Application of coherent optical transition radiation (COTR) diagnostics to compact accelerators has been demonstrated for the laser-driven plasma accelerator case recently. It is proposed that such diagnostics for beam size, beam divergence, microbunching fraction, spectral content, and bunch length would be useful before and after any subsequent acceleration in crystals or nanostructures. In addition, there are indications that under some scenarios a microbunched beam could resonantly excite wake fields in nanostructures that might lead to an increased acceleration gradient.
Holographic complexity from Crofton’s formula in Lorentzian AdS3
Authors: Huang Xing , Zhang Le
Published: January 2020

We study Crofton’s formula in the Lorentzian AdS3 and find that the area of a generic spacelike two-dimensional surface is given by the flux of spacelike geodesics. The “complexity[Formula: see text]=[Formula: see text]volume” conjecture then implies a new holographic representation of complexity in terms of the number of geodesics. Finally, we explore the possible explanation of this result from the standpoint of information theory.
A hybrid soft computing-based clustering protocol for wireless sensor networks
Authors: Kaur Supreet , Joshi Vijay Kumar
Published: January 2020

In this paper, an inter-cluster data aggregation based on General Self-Organized Tree-based Energy Balance (GSTEB) routing protocol has been improved by proposing energy efficient protocol under hybrid soft computing. First, finest cluster heads are elected by using enhanced ant colony optimization (ACO) method. After that, information which has been gathered by cluster heads is sent to sink node by applying hybrid soft computing (i.e., hybridization of glow swarm and ACOs). Experimental analysis shows that network lifetime has been improved according to the proposed procedure in contrast with already available procedures.
Novel elastic evolution of carbide Mo2Ga2C under pressure: Ab initio theoretical investigation
Authors: Wu Rui , Wang Hai-Chen , Yang Yan , Ma Li , Jiang Shan , Yang Min , Tang Bi-Yu
Published: January 2020

The pressure dependence of elastic properties of Mo2Ga2C is studied via first-principles calculation. The present investigation shows that differing from other MAX phases, in Mo2Ga2C the [Formula: see text] is larger than [Formula: see text], because of the strong Ga–Ga interlayer bonds along [Formula: see text]-axis. Moreover, under pressure, the [Formula: see text] increases more rapidly, originating from the faster strengthening of Ga–Ga bonds. Interestingly, elastic constants [Formula: see text] soften under high pressure (more than 20 GPa). Especially, the calculated phonon structure demonstrates that transverse acoustic (TA) phonon mode also softens under pressure, implying possible phase transition. The reduction of [Formula: see text] and softening of phonon mode are attributed to significantly weakened Mo–Mo interaction in contrast to the strengthening of Ga–Ga bonds under high pressure. Our present results further indicate that Mo2Ga2C is more ductile under pressure.
Multi-band and broadband metamaterial perfect absorber based on conductive polymer and near-field coupling
Authors: Tuyen Le Dac , Linh Pham The , Luu Dang Hong , Phuong Le Danh , Tuan Tong Ba , Cuong Tran Manh , Lam Vu Dinh
Published: January 2020

We present a simple method for enhancing the bandwidth and absorptivity of metamaterial perfect absorber (MPA)-formed disk resonators. Utilizing low-conductivity polymer and near-field coupling of multi-band resonances, a 6.8 GHz broadband MPA is achieved with absorption over 90%. The proposed MPA also shows polarization-independent absorption behavior. Furthermore, the structural design is useful for making broadband MPA and can be applied to higher frequencies with a simple configuration.
LOWER ASSOUAD-TYPE DIMENSIONS OF UNIFORMLY PERFECT SETS IN DOUBLING METRIC SPACES
Authors: CHEN HAIPENG , WU MIN , CHANG YUANYANG
Published: January 2020

In this paper, we are concerned with the relationship among the lower Assouad-type dimensions. For uniformly perfect sets in doubling metric spaces, we obtain a variational result between two different but closely related lower Assouad spectra. As an application, we show that the limit of the lower Assouad spectrum as [Formula: see text] tends to 1 is equal to the quasi-lower Assouad dimension, which provides an equivalent definition to the latter. On the other hand, although the limit of the lower Assouad spectrum as [Formula: see text] tends to 0 exists, there exist uniformly perfect sets such that this limit is not equal to the lower box-counting dimension. Moreover, by the example of Cantor cut-out sets, we show that the new definition of quasi-lower Assouad dimension is more accessible, and indicate that the lower Assouad dimension could be strictly smaller than the lower spectra and the quasi-lower Assouad dimension.
LIMIT BEHAVIOR OF THE QUASI-LINEAR DISCRETE FUNCTIONS
Authors: LÜ XIAOTAO , CHEN JIN , WEN ZHIXIONG , WU WEN
Published: January 2020

In this paper, we focus on the limit behavior of the quasi-linear functions, including some [Formula: see text]-regular sequences. The limit behavior of the quasi-linear functions is presented through their induced limit functions. We show that these limit functions are continuous and self-similar. Moreover, the graphs of the limit functions are fractal curves. We give an estimation of the upper and lower box dimensions of the graphs of the limit functions. Under certain condition, the exact value of the box dimensions of the graphs of the limit functions is obtained.
SCALING ANALYSIS OF THE A-PHASE DYNAMICS DURING SLEEP
Authors: ARCE-GUEVARA V. E. , MENDEZ M. O. , MURGUÍA J. S. , ALBA A. , GONZÁLEZ-AGUILAR H. , PALACIOS-HERNÁNDEZ E. R.
Published: January 2020

In this work, the scaling behavior of the sleep process is evaluated by using detrended fluctuation analysis based on wavelets. The analysis is carried out from arrivals of short and recurrent cortical events called A-phases, which in turn build up the Cyclic Alternating Pattern phenomenon, and are classified in three types: A1, A2 and A3. In this study, 61 sleep recordings corresponding to healthy, nocturnal frontal lobe epilepsy patients and sleep-state misperception subjects, were analyzed. From the A-phase annotations, the onsets were extracted and a binary sequence with one second resolution was generated. An item in the sequence has a value of one if an A-phase onset occurs in the corresponding window, and a value of zero otherwise. In addition, we consider other different temporal resolutions from 2[Formula: see text]s to 256[Formula: see text]s. Furthermore, the same analysis was carried out for sequences obtained from the different types of A-phases and their combinations. The results of the numerical analysis showed a relationship between the time resolutions and the scaling exponents; specifically, for higher time resolutions a white noise behavior is observed, whereas for lower time resolutions a behavior towards to [Formula: see text]-noise is exhibited. Statistical differences among groups were observed by applying various wavelet functions from the Daubechies family and choosing the appropriate sequence of A-phase onsets. This scaling analysis allows the characterization of the free-scale dynamic of the sleep process that is specific for each sleep condition. The scaling exponent could be useful as a diagnosis parameter in clinics when sleep macrostructure does not offer enough information.
The Direct Role of Anticipated Regret in the Formation of Student’s Entrepreneurial Intention
Authors: Bouderbala Rym
Published: January 2020

The most widely used entrepreneurial intention models explain only cognitive motivational factors. However, psychological studies reveal that emotional factors and counterfactual thinking such as anticipated affect also explain the intention and then behaviour. The objective of this research is to identify the role of anticipated regret in forming students’ entrepreneurial intentions. To test the hypotheses of the conceptual model integrating anticipated regret among the antecedent motivational factors to entrepreneurial intention, a hierarchical regression technique has been adopted. Data have been collected from 266 students in management degree. Our results show that anticipated regret, as well as attitude towards business start-up and perceived behavioural control, have a direct and positive influence on entrepreneurial intention described in the theory of planned behaviour. This study contributes to extend prior cognition-based explanations of the origin of earlier stages in an entrepreneurial journey.
Common Representational Model and Ontologies for Effective Law Enforcement Solutions
Authors: Kozik Rafal , Choras Michal , Pawlicki Marek , Holubowicz Witold , Pallmer Dirk , Mueller Wilmuth , Behmer Ernst-Josef , Loumiotis Ioannis , Demestichas Konstantinos , Horincar Roxana , Laudy Claire , Faure David
Published: January 2020

Ontologies have developed into a prevailing technique for establishing semantic interoperability among heterogeneous systems transacting information. An ontology is an unambiguous blueprint of a concept. For Artificial Intelligence, only the defined notions can be considered existent. Thus, in relation to AI, an ontology can be understood as part of a program which delineates a collection of descriptions. An ontology, therefore, correlates the labels of the entities in the universe of discourse with wording that holds meaning for humans, explaining what those labels signify, along with the precise principles that force the interpretation and semantic utilization of these labels. An ontology constitutes a proper statement of a logical theory. It is a crucial component of a system with the capability to process, manage, analyze, correlate and reason from the large datasets characterized by heterogeneity. This paper depicts the process of development of a Common Representational Model (CRM) on top of several ontologies, taxonomies and classifications to facilitate computational and data mining functionalities. The building blocks of said CRM are delineated in detail, as well as its application in a specific use case.
Harnessing Nature’s Diversity for Developing New Biotechnologies
Authors: Zhang Feng
Published: January 2020

Molecular biologists today make use of a number of technologies based on natural products or systems, essentially using the wonders of life to further discover wonderous things about life. This cycle is powered by the immense amount of natural diversity. Here I highlight how one natural system, CRISPR, has been engineered for a range of applications aimed at improving human health and discuss possible ways natural diversity may be leveraged in the future.
On Becoming a Physicist of Mind
Authors: Levelt Willem J.M.
Published: January 2020

In 1976, the German Max Planck Society established a new research enterprise in psycholinguistics, which became the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands. I was fortunate enough to be invited to direct this institute. It enabled me, with my background in visual and auditory psychophysics and the theory of formal grammars and automata, to develop a long-term chronometric endeavor to dissect the process of speaking. It led, among other work, to my book Speaking (1989) and to my research team's article in Brain and Behavioral Sciences “A Theory of Lexical Access in Speech Production” (1999). When I later became president of the Royal Netherlands Academy of Arts and Sciences, I helped initiate the Women for Science research project of the Inter Academy Council, a project chaired by my physicist sister at the National Institute of Standards and Technology. As an emeritus I published a comprehensive History of Psycholinguistics (2013). As will become clear, many people inspired and joined me in these undertakings.
The Syntax of Adverbials
Authors: Ernst Thomas
Published: January 2020

After explicit phrase structure rules were abandoned in government–binding theory, some account of the distribution of adverbials became necessary. This review surveys two current theories. The first, often called the scopal theory, posits that the main factor is semantics: In general, adverbials can appear wherever they cause no violation of semantic well-formedness. Purely syntactic and morphological factors play a role, but it is a relatively minor one. Though the scopal theory predicts a significant range of adverbial distribution correctly, much of its underlying semantic analysis remains to be developed in explicit terms. The second theory discussed in this review, the cartographic theory, takes syntax as central, proposing that adverbials are individually licensed by dedicated functional heads, arranged in a rigid hierarchy by Universal Grammar. This approach has some empirical successes but also a number of problems; thus, the scopal theory is more likely to represent the right direction.
Antipassives in Crosslinguistic Perspective
Authors: Heaton Raina
Published: January 2020

Recent descriptive and typological research on antipassives has allowed many existing claims about antipassives to be reevaluated. Although there is still debate about which characteristics are necessary and sufficient for a construction to be considered an antipassive, it is clear that antipassives indicated by verbal marking are more widespread than previously thought. Parameters such as whether the patient can be expressed as an oblique argument, whether the antipassive is lexically restricted, and whether the antipassive is obligatory are important factors in the distribution and classification of antipassive constructions. Additionally, antipassive functions are more varied than often described, and do not necessarily correlate with morphological or syntactic ergativity.
Language and Masculinities: History, Development, and Future
Authors: Lawson Robert
Published: January 2020

In the past two decades, the field of language and masculinities studies has become an established part of language, gender, and sexuality research, growing in response to concerns about the limited criticality directed toward men and masculinities in sociolinguistics. In doing so, the field has added to the conceptual and theoretical tool kit of sociolinguistics, furthering both our understanding of the linguistic strategies used by men in a variety of contexts and the myriad links connecting language and the social performance of gender. This review surveys the historical trajectory of scholarship broadly concerned with men, masculinities, and language and charts its development from more critical work on men and masculinities within sociology to its emergence as an independent field of inquiry. I outline some of the key contributions this body of work has made to sociolinguistic theory, methodology, and knowledge and suggest some future research directions through which the field may engage with contemporary social issues.
An Experimental and Finite Element Modeling Approach to Determining Degradation of Aircraft Coating Systems
Authors: Policastro Steve , Iezzi Erick , Hangarter Carlos , Anderson Rachel , Arcari Attilio , Strom Matthew
Published: January 2020

In order to delay the onset of corrosion structures subjected to atmospheric degradation, such as aircraft, exterior metal surfaces are frequently covered in a corrosion prevention organic coating system. Organic coating systems, in many cases, provide a reservoir of corrosion inhibitors along with establishing a critical electrolyte barrier between the atmosphere and the structure. These coating systems include a surface pretreatment, a primer barrier layer that can contain a sacrificial inhibitor additive, and a topcoat that also provides corrosion barrier properties and other additives for color. Improving our understanding, and modeling how these coating properties change, as a function of exposure to a variety of service environments can decrease maintenance costs associated with paint removal, and re-painting. A model that can incorporate the fundamental effects of various environmental parameters can provide damage predictions based upon the measured environmental data.To that end, the initial phase of this program has focused on testing and monitoring a US Navy aircraft coating system, exposed to a variety of degradation conditions that simulate the extreme ranges of environmental stresses expected to be seen in-service. Coating condition was monitored using electrochemical impedance spectroscopy (EIS) and characterized using equivalent-circuit models so that changes to the coating system properties could be quantified and tracked over time.
Predictions of Apoptosis Proteins by Integrating Different Features Based on Improving Pseudo‐Position‐Specific Scoring Matrix
Authors: Ruan Xiaoli , Zhou Dongming , Nie Rencan , Guo Yanbu
Published: January 2020

Apoptosis proteins are strongly related to many diseases and play an indispensable role in maintaining the dynamic balance between cell death and division in vivo. Obtaining localization information on apoptosis proteins is necessary in understanding their function. To date, few researchers have focused on the problem of apoptosis data imbalance before classification, while this data imbalance is prone to misclassification. Therefore, in this work, we introduce a method to resolve this problem and to enhance prediction accuracy. Firstly, the features of the protein sequence are captured by combining Improving Pseudo‐Position‐Specific Scoring Matrix (IM‐Psepssm) with the Bidirectional Correlation Coefficient (Bid‐CC) algorithm from position‐specific scoring matrix. Secondly, different features of fusion and resampling strategies are used to reduce the impact of imbalance on apoptosis protein datasets. Finally, the eigenvector adopts the Support Vector Machine (SVM) to the training classification model, and the prediction accuracy is evaluated by jackknife cross‐validation tests. The experimental results indicate that, under the same feature vector, adopting resampling methods remarkably boosts many significant indicators in the unsampling method for predicting the localization of apoptosis proteins in the ZD98, ZW225, and CL317 databases. Additionally, we also present new user‐friendly local software for readers to apply; the codes and software can be freely accessed at https://github.com/ruanxiaoli/Im-Psepssm.
AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia
Authors: Yi Xue , Sarkar Aloke , Kismali Gorkem , Aslan Burcu , Ayres Mary , Iles LaKesla R. , Keating Michael J. , Wierda William G. , Long James P. , Bertilaccio Maria Teresa Sabrina , Gandhi Varsha
Published: January 2020

Purpose:

Survival of CLL cells due to the presence of Bcl-2 and Mcl-1 has been established. Direct inhibition of Bcl-2 by venetoclax and indirect targeting of Mcl-1 with transcription inhibitors have been successful approaches for CLL. AMG-176 is a selective and direct antagonist of Mcl-1, which has shown efficacy in several hematologic malignancies; however, its effect on CLL is elusive. We evaluated biological and molecular effects of AMG-176 in primary CLL cells.

Experimental Design:

Using samples from patients (n = 74) with CLL, we tested effects of AMG-176 on CLL and normal hematopoietic cell death and compared importance of CLL prognostic factors on this biological activity. We evaluated CLL cell apoptosis in the presence of stromal cells and identified cell death pathway including stabilization of Mcl-1 protein. Finally, we tested a couplet of AMG-176 and venetoclax in CLL lymphocytes.

Results:

AMG-176 incubations resulted in time- and dose-dependent CLL cell death. At 100 and 300 nmol/L, there was 30% and 45% cell death at 24 hours. These concentrations did not result in significant cell death in normal hematopoietic cells. Presence of stroma did not affect AMG-176–induced CLL cell death. IGHV unmutated status, high β2M and Mcl-1 protein levels resulted in slightly lower cell death. Mcl-1, but not Bcl-2 protein levels, in CLL cells increased with AMG-176. Low concentrations of venetoclax (1–30 nmol/L) were additive or synergistic with AMG-176.

Conclusions:

AMG-176 is active in inducing CLL cell death while sparing normal blood cells. Combination with low-dose venetoclax was additive or synergistic.
A Combinatorial Strategy for TargetingBRAFV600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)
Authors: Ghosh Chandrayee , Kumar Suresh , Kushchayeva Yevgeniya , Gaskins Kelli , Boufraqech Myriem , Wei Darmood , Gara Sudheer Kumar , Zhang Lisa , Zhang Ya-qin , Shen Min , Mukherjee Sanjit , Kebebew Electron
Published: January 2020

Purpose:

Most aggressive thyroid cancers are commonly associated with a BRAFV600E mutation. Preclinical and clinical data in BRAFV600E cancers suggest that combined BRAF and MEK inhibitor treatment results in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signaling by alternate pathways. We hypothesized that combination therapy with BRAF and multitargeting TK inhibitors (MTKI) might be more effective in BRAFV600E thyroid cancer than in single-agent or BRAF and MEK inhibitors.

Experimental Design:

The combined drug activity was analyzed to predict any synergistic effect using high-throughput screening (HTS) of active drugs. We performed follow-up in vitro and in vivo studies to validate and determine the mechanism of action of synergistic drugs.

Results:

The MTKI ponatinib and the BRAF inhibitor PLX4720 showed synergistic activity by HTS. This combination significantly inhibited proliferation, colony formation, invasion, and migration in BRAFV600E thyroid cancer cell lines and downregulated pERK/MEK and c-JUN signaling pathways, and increased apoptosis. PLX4720-resistant BRAFV600E cells became sensitized to the combination treatment, with decreased proliferation at lower PLX4720 concentrations. In an orthotopic thyroid cancer mouse model, combination therapy significantly reduced tumor growth (P < 0.05), decreased the number of metastases (P < 0.05), and increased survival (P < 0.05) compared with monotherapy and vehicle control.

Conclusions:

Combination treatment with ponatinib and PLX4720 exhibited significant synergistic anticancer activity in preclinical models of BRAFV600E thyroid cancer, in addition to overcoming PLX4720 resistance. Our results suggest this combination should be tested in clinical trials.
Gene Expression Signatures Identify Novel Therapeutics for Metastatic Pancreatic Neuroendocrine Tumors
Authors: Scott Aaron T. , Weitz Michelle , Breheny Patrick J. , Ear Po Hien , Darbro Benjamin , Brown Bart J. , Braun Terry A. , Li Guiying , Umesalma Shaikamjad , Kaemmer Courtney A. , Maharjan Chandra K. , Quelle Dawn E. , Bellizzi Andrew M. , Chandrasekharan Chandrikha , Dillon Joseph S. , O'Dorisio Thomas M. , Howe James R.
Published: January 2020

Purpose:

Pancreatic neuroendocrine tumors (pNETs) are uncommon malignancies noted for their propensity to metastasize and comparatively favorable prognosis. Although both the treatment options and clinical outcomes have improved in the past decades, most patients will die of metastatic disease. New systemic therapies are needed.

Experimental Design:

Tissues were obtained from 43 patients with well-differentiated pNETs undergoing surgery. Gene expression was compared between primary tumors versus liver and lymph node metastases using RNA-Seq. Genes that were selectively elevated at only one metastatic site were filtered out to reduce tissue-specific effects. Ingenuity pathway analysis (IPA) and the Connectivity Map (CMap) identified drugs likely to antagonize metastasis-specific targets. The biological activity of top identified agents was tested in vitro using two pNET cell lines (BON-1 and QGP-1).

Results:

A total of 902 genes were differentially expressed in pNET metastases compared with primary tumors, 626 of which remained in the common metastatic profile after filtering. Analysis with IPA and CMap revealed altered activity of factors involved in survival and proliferation, and identified drugs targeting those pathways, including inhibitors of mTOR, PI3K, MEK, TOP2A, protein kinase C, NF-kB, cyclin-dependent kinase, and histone deacetylase. Inhibitors of MEK and TOP2A were consistently the most active compounds.

Conclusions:

We employed a complementary bioinformatics approach to identify novel therapeutics for pNETs by analyzing gene expression in metastatic tumors. The potential utility of these drugs was confirmed by in vitro cytotoxicity assays, suggesting drugs targeting MEK and TOP2A may be highly efficacious against metastatic pNETs. This is a promising strategy for discovering more effective treatments for patients with pNETs.
Localized Bronchial Hyperemia in Cases of Iatrogenic Hemoptysis: Clinical Presentations and Pathophysiological Mechanisms
Authors: Touman Abdelfattah , Vitsas Vlasios , Leonidas Angelakis , Freitag Lutz , Stratakos Grigoris K.
Published: January 2020

Hemoptysis is a frequently encountered symptom in many clinical settings, and etiologic diagnosis can sometimes prove challenging. Bronchoscopy may not promptly reveal the source or the cause of bleeding and few reports have focused so far on the abnormalities of bronchial mucosa vasculature that may unveil the underlying pathophysiology. In this special feature article, we present a series of cases presenting with hemoptysis after angiographic interventions in the thoracic vessels. Localized hyperemia and vascular dilatations in the bronchial mucosa observed during bronchoscopy as unique findings became clues enabling the correct diagnosis and management. We suggest the relevant pathophysiological mechanisms and discuss the available published experience on similar clinical entities.
Clinically Significant Visual Deficits after Laser Interstitial Thermal Therapy for Mesiotemporal Epilepsy
Authors: Jermakowicz Walter J. , Wu Chengyuan , Neal Elliot , Cajigas Iahn , D’Haese Pierre-François , Donahue David J. , Sharan Ashwini D. , Vale Fernando L. , Jagid Jonathan R.
Published: January 2020

Background: Laser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking. Objectives: To evaluate the visual deficits that occur after LITT for mTLE and their etiology. Method: We surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution. Results: Of 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was ­associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer’s loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory. Conclusions: LITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure.
Lymph Node Ratio Can Better Predict Prognosis than Absolute Number of Positive Lymph Nodes in Operable Cervical Carcinoma
Authors: Widschwendter Peter , Polasik Arkadius , Janni Wolfgang , de Gregorio Amelie , Friedl Thomas W.P. , de Gregorio Nikolaus
Published: January 2020

Background: Nodal status is the most important prognostic factor in cervical cancer. However, further risk stratification in node positive cervical cancer patients is warranted for optimal therapeutic decisions. Material and Methods: Nodal positive patients (n = 86) were retrospectively stratified into two groups according to either number of positive nodes (>3 vs. 1–3) or lymph node ratio (LNR) (≥10 vs. <10% and >6.6 vs. ≤6.6%). Univariable log-rank tests and both univariable and adjusted multivariable Cox regression models were used to evaluate the association between number of positive nodes or LNR and disease-free survival (DFS) and overall survival (OS). Results: LNR was significantly associated with worse DFS in adjusted multivariable analysis, both when categorized as ≥10 versus <10% (HR 2.25, 95% CI 1.06–4.76, p = 0.034) and when categorized as >6.6 versus ≤6.6% (HR 2.79, 95% CI 1.23–6.37, p = 0.015). However, we found no significant association between number of positive nodes or LNR and OS. Discussion:In operable node-positive cervical cancer, both number of positive lymph nodes and LNR can be used for further risk stratification with regard to DFS but not OS.
Incidence of Sports-Related Traumatic Brain Injury of All Severities: A Systematic Review
Authors: Theadom Alice , Mahon Susan , Hume Patria , Starkey Nicola , Barker-Collo Suzanne , Jones Kelly , Majdan Marek , Feigin Valery L.
Published: January 2020

Introduction: Whilst there are many benefits to participating in sports and recreational activities, there is also a risk of injury including sports-related traumatic brain injury ­(SR-TBI). To inform injury prevention initiatives, it is important to explore the burden of SR-TBI at the population level. This review aimed to estimate the incidence of SR-TBI in the general population across injury severities. Methods: Systematic search of electronic databases using keywords from 1965 until June 2019 facilitated by hand searches of reference lists. Original research reporting on the incidence of SR-TBI, capturing people of all ages in a well-defined population area was included. Studies were excluded if they focused on a specific sport(s) or population group. All studies were required to be published in the English language. Quality of studies was determined as poor, moderate or good based on the standards of reporting of neurological disorders criteria. Data on year(s) of data collection, diagnostic criterion, case ascertainment sources, population denominator and incidence per 100,000 and by age, sex, injury severity and sport were extracted by 2 authors independently using a standard data extraction form. Results: Following review of 11 studies meeting the inclusion criteria, the incidence of SR-TBI within hospital-based studies ranged between 3.5 and 31.5 per 100,000. One community-based study using multiple case ascertainment sources identified a higher incidence of 170 per 100,000. SR-TBI accounted for 1.2–30.3% of all TBIs. One study provided incidence data across a 5-year period suggesting an increasing trend in incidence over time. Males were more at risk than females (66.1–75.6%), and adolescents and young adults had the highest incidence of SR-TBI. Conclusion: The primary objective of this review was to provide a summary of descriptive data on SR-TBI epidemiology at the population level. SR-TBI represented up to one-third of all causes of TBI. Trends in incidence by age and sport were challenging to determine due to lack of consistency in reporting as well as the small number of studies overall. Undertaking injury surveillance at all levels of TBI will assist with understanding the nature, mechanism of and surrounding events where injuries occur in sport.
Thyroid Carcinoma: Do We Need to Treat Men and Women Differently?
Authors: Lorenz Kerstin , Schneider Rick , Elwerr Malik
Published: January 2020

Background: For differentiated thyroid carcinoma, gender-specific differences exist in regard to incidence, age at onset, tumor stage, and recurrence, but causative factors remain to be elucidated. Possible and likely contributors are genetic and hormonal differences. While some of these factors are known to be differently distributed between the sexes, like, for example, BRAF-mutation and estrogen levels, their role in thyroid cancer initiation or promotion awaits further investigation. Summary: Apart from generally accepted risk factors for differentiated thyroid carcinoma, an apparent gender disparity of thyroid cancer with a general female predominance, an age-dependent difference in growth acceleration during the reproductive years, and a peak at the time of entering menopause have been demonstrated. Hormonal status and hormonal receptor mediation seem to be most likely to contribute to the differences in thyroid cancer phenotypes of males and females. However, specific cause-and-effect pathways have not yet been determined. Key Messages: Female gender is overrepresented in the incidence of differentiated thyroid carcinoma, as it is in the more favorable tumor stages. Besides the assumption of gender-specific differences in general health awareness and behavior, hormonal age-dependent and gender-specific factors appear to be contributory. In the advanced stage of thyroid cancer, males are overrepresented. Therefore, the real cause of gender differences in thyroid cancer is likely due to a mixed effect. Present knowledge does not favor different treatment modalities of thyroid carcinoma according to gender.