bluuebunny/crossref_metadata_2025 huggingface dataset:
CD8+CD103+ tissue-resident memory T cells convey reduced protective immunity in cutaneous squamous cell carcinoma
Authors: Lai Chester , Coltart George , Shapanis Andrew , Healy Conor , Alabdulkareem Ahmad , Selvendran Sara , Theaker Jeffrey , Sommerlad Matthew , Rose-Zerilli Matthew , Al-Shamkhani Aymen , Healy Eugene
Published: January 2021

Background

Tumor infiltrating lymphocytes play a key role in antitumor responses; however, while several memory T-cell subtypes have been reported in inflammatory and neoplastic conditions, the proportional representation of the different subsets of memory T cells and their functional significance in cancer is unclear. Keratinocyte skin cancer is one of the most common cancers globally, with cutaneous squamous cell cancer (cSCC) among the most frequent malignancies capable of metastasis.

Methods

Memory T-cell subsets were delineated in human cSCCs and, for comparison, in non-lesional skin and blood using flow cytometry. Immunohistochemistry was conducted to quantify CD103+ cells in primary human cSCCs which had metastasized (P-M) and primary cSCCs which had not metastasized (P-NM). TIMER2.0 (timer.cistrome.org) was used to analyze TCGA cancer survival data based onITGAEexpression. Immunofluorescence microscopy was performed to determine frequencies of CD8+CD103+ cells in P-M and P-NM cSCCs.

Results

Despite intertumoral heterogeneity, most cSCC T cells were CCR7−/CD45RA− effector/resident memory (TRM) lymphocytes, with naive, CD45RA+/CCR7− effector memory re-expressing CD45RA, CCR7+/L-selectin+ central memory and CCR7+/L-selectin− migratory memory lymphocytes accounting for smaller T-cell subsets. The cSCC CD8+ T-cell population contained a higher proportion of CD69+/CD103+ TRMs than that in non-lesional skin and blood. These cSCC CD69+/CD103+ TRMs exhibited increased IL-10 production, and higher CD39, CTLA-4 and PD-1 expression compared with CD103− TRMs in the tumor. CD103+ cells were more frequent in P-M than P-NM cSCCs. Analysis of TCGA data demonstrated that high expression ofITGAE(encoding CD103) was associated with reduced survival in primary cutaneous melanoma, breast carcinoma, renal cell carcinoma, kidney chromophobe cancer, adrenocortical carcinoma and lower grade glioma. Immunofluorescence microscopy showed that the majority of CD103 was present on CD8+ T cells and that CD8+CD103+ cells were significantly more frequent in P-M than P-NM cSCCs.

Conclusion

These results highlight CD8+CD103+ TRMs as an important functional T-cell subset associated with poorer clinical outcome in this cancer.
Monitored anesthesia care during mechanical thrombectomy for stroke: need for data-driven and individualized decisions
Authors: Nogueira Raul G , Mohammaden Mahmoud H , Moran Timothy P , Whalin Matthew K , Gershon Raphael Y , Al-Bayati Alhamza R R , Ratcliff Jonathan , Pisani Leonardo , Liberato Bernardo , Bhatt Nirav , Frankel Michael R , Haussen Diogo C
Published: January 2021

Background

The optimal anesthesia management for patients with stroke undergoing mechanical thrombectomy (MT) during the COVID-19 pandemic has become a matter of controversy. Some recent guidelines have favored general anesthesia (GA) in patients perceived as high risk for intraprocedural conversion from sedation to GA, including those with dominant hemispheric occlusions/aphasia or baseline National Institutes of Health Stroke Scale (NIHSS) score >15. We aim to identify the rate and predictors of conversion to GA during MT in a high-volume center where monitored anesthesia care (MAC) is the default modality.

Methods

A retrospective review of a prospectively maintained MT database from January 2013 to July 2020 was undertaken. Analyses were conducted to identify the predictors of intraprocedural conversion to GA. In addition, we analyzed the GA conversion rates in subgroups of interest.

Results

Among 1919 MT patients, 1681 (87.6%) started treatment under MAC (median age 65 years (IQR 55–76); baseline NIHSS 16 (IQR 11–21); 48.4% women). Of the 1677 eligible patients, 26 (1.6%) converted to GA including 1.4% (22/1615) with anterior and 6.5% (4/62) with posterior circulation strokes. The only predictor of GA conversion was posterior circulation stroke (OR 4.99, 95% CI 1.67 to 14.96, P=0.004). The conversion rates were numerically higher in right than in left hemispheric occlusions (1.6% vs 1.2%; OR 1.37, 95% CI 0.59 to 3.19, P=0.47) and in milder than in more severe strokes (NIHSS ≤15 vs >15: 2% vs 1.2%; OR 0.62, 95% CI 0.28 to 1.36, P=0.23).

Conclusions

Our study showed that the overall rate of conversion from MAC to GA during MT was low (1.6%) and, while higher in posterior circulation strokes, it was not predicted by either hemispheric dominance or stroke severity. Caution should be given before changing clinical practice during moments of crisis.
Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments
Authors: Garcia-Aymerich Judith , Puhan Milo A , Corriol-Rohou Solange , de Jong Corina , Demeyer Heleen , Dobbels Fabienne , Erzen Damijan , Frei Anja , Gimeno-Santos Elena , Hopkinson Nicholas S , Ivanoff Nathalie , Karlsson Niklas , Louvaris Zafeiris , Polkey Michael I , Rabinovich Roberto A , Scuri Mario , Tabberer Maggie , Vogiatzis Ioannis , Troosters Thierry
Published: January 2021

Background

The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients’ experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.

Objective

To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.

Methods

We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.

Results

We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score.

Conclusions

The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.
Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers
Authors: Zhang Yingze , Tedrow John , Nouraie Mehdi , Li Xiaoyun , Chandra Divay , Bon Jessica , Kass Daniel J , Fuhrman Carl R , Leader Joseph K , Duncan Steven R , Kaminski Naftali , Sciurba Frank C
Published: January 2021

Background

Pentraxin 3 (PTX3) influences innate immunity and inflammation, host defence, the complement cascade and angiogenesis. PTX3 expression in lung and blood of subjects with tobacco exposure, and its potential relationship with disease pattern and clinical outcome are poorly understood.

Methods

Using independent platforms and cohorts, we identified associations of PTX3 gene expression in lung tissue and plasma from current and former tobacco smokers (with and without chronic obstructive pulmonary disease, COPD) to disease phenotypes including quantitative CT determined emphysema, lung function, symptoms and survival. Two putative regulatory variants of the PTX3 gene were examined for association with COPD manifestations. The relationship between plasma PTX3 and hyaluronic acid levels was further examined.

Results

PTX3 gene expression in lung tissue was directly correlated with emphysema severity (p<0.0001). Circulating levels of PTX3 were inversely correlated with FEV1 (p=0.006), and positively associated with emphysema severity (p=0.004) and mortality (p=0.008). Two PTX3 gene regulatory variants were associated with a lower risk for emphysema and expiratory airflow obstruction, and plasma levels of PTX3 and hyaluronic acid were related.

Conclusions

These data show strong and overlapping associations of lung and blood PTX3 levels, and PTX3 regulatory gene variants, with the severity of airflow obstruction, emphysema and mortality among smokers. These findings have potential implications regarding the pathogenesis of smoking-related lung diseases and warrant further exploration for the use of PTX3 as a predictive biomarker.
An enhanced care package to improve asthma management in Malawian children: a randomised controlled trial
Authors: Rylance Sarah , Chinoko Beatrice , Mnesa Bright , Jewell Chris , Grigg Jonathan , Mortimer Kevin
Published: January 2021

Background

Shortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles.

Methods

We conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6–15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence.

Findings

Between September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, p<0.001). Fewer intervention children attended emergency healthcare (7.3% vs 25.4%, p=0.02) and missed school (20.0% vs 62.7%, p<0.001) compared with standard care children.

Interpretation

The intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings.

Trial registration number

PACTR201807211617031.
Long-term changes in body condition and gillnet selectivity in Lake Constance pelagic spawning whitefish (Coregonus wartmanni)
Authors: DeWeber J. Tyrell , Rösch Roland , Baer Jan , Brinker Alexander
Published: January 2021

The body condition of Lake Constance pelagic spawning whitefish (Coregonus wartmanni) has changed substantially during the past century and altered the length-based selectivity of gillnets. Linked hierarchical models using Bayesian inference and error propagation were used to estimate the monthly body condition of whitefish from 1932 to 2018 and condition-dependent gillnet selectivity from 1964 to 2018. As expected, body condition followed past trends in nutrient dynamics and was highest in summer months. Body condition was clearly linked to gillnet selectivity, with a weight increase of a 300 mm whitefish from 205 to 260 g predicted to reduce the mean (from 374 to 330 mm) and standard deviation (from 30.8 to 25.1 mm) of lengths selected by a 38 mm mesh gillnet. Simulations demonstrate that such changes can reduce the mean age in harvest by over 1 year and greatly bias population age distribution estimates if selectivity changes are ignored. Similar variation in gillnet selectivity is expected where trophic conditions or other factors cause body condition differences, and accounting for these changes could reduce biases to inform fishery management.
A unified quark-nuclear matter equation of state from the cluster virial expansion within the generalized Beth–Uhlenbeck approach
Authors: Bastian Niels-Uwe Friedrich , Blaschke David Bernhard
Published: January 2021

We consider a cluster expansion for strongly correlated quark matter where the clusters are baryons with spectral properties that are described within the generalized Beth–Uhlenbeck approach by a medium dependent phase shift. We employ a simple ansatz for the phase shift which describes an on-shell bound state with an effective mass and models the continuum by an anti-bound state located at the mass of the three-quark continuum threshold, so that the Levinson theorem is fulfilled by construction. The quark and baryon interactions are accounted for by the coupling to scalar and vector meson mean fields modelled by density functionals. At increasing density and temperature, due to the different medium-dependence of quark and baryon masses, the Mott dissociation of baryons occurs and its contributions to the thermodynamics vanish. It is demonstrated on this simple example that this unified approach to quark-hadron matter is capable of describing crossover as well as first order phase transition behaviour in the phase diagram with a critical endpoint. Changing the meson mean field, the case of a “crossover all over” in the phase diagram is also obtained.
Mean-field BCS theory of the Meissner effect in bulk revisited
Authors: Bányai Ladislaus Alexander
Published: January 2021

We show that the implementation of the $$1/ c^2 $$

1
/

c
2

transverse current–current interaction between electrons resulting from the non-relativistic QED into the standard self-consistent electron BCS model in bulk under thermal equilibrium in the stable superconductive phase ensures the full compensation of a constant external magnetic field by the internal magnetic field created by the electrons, i.e. one has an ideal diamagnet.

GraphicAbstract
Non-linear plane gravitational waves as space-time defects
Authors: Carneiro F. L. , Ulhoa S. C. , Maluf J. W. , da Rocha-Neto J. F.
Published: January 2021

We consider non-linear plane gravitational waves as propagating space-time defects, and construct the Burgers vector of the waves. In the context of classical continuum systems, the Burgers vector is a measure of the deformation of the medium, and at a microscopic (atomic) scale, it is a naturally quantized object. One purpose of the present article is ultimately to probe an alternative way on how to quantize plane gravitational waves.
Induced THz transitions in Rydberg caesium atoms for application in antihydrogen experiments
Authors: Vieille-Grosjean M. , Dimova E. , Mazzotta Z. , Comparat D. , Wolz T. , Malbrunot C.
Published: January 2021

Antihydrogen atoms are produced at CERN in highly excited Rydberg states. However, precision measurements require anti-atoms in ground state. Whereas experiments currently rely on spontaneous emission only, simulations have shown that THz light can be used to stimulate the decay towards ground state and thus increase the number of anti-atoms available for measurements. We review different possibilities at hand to generate light in the THz range required for the purpose of stimulated deexcitation. We demonstrate the effect of a blackbody type light source, which however presents drawbacks for this application including strong photoionization. Further, we report on the first THz transitions in a beam of Rydberg caesium atoms induced by photomixers and conclude with the implications of the results for the antihydrogen case.

Graphic abstract
Dark Web Marketplaces and COVID-19: before the vaccine
Authors: Bracci Alberto , Nadini Matthieu , Aliapoulios Maxwell , McCoy Damon , Gray Ian , Teytelboym Alexander , Gallo Angela , Baronchelli Andrea
Published: January 2021

The COVID-19 pandemic has reshaped the demand for goods and services worldwide. The combination of a public health emergency, economic distress, and misinformation-driven panic have pushed customers and vendors towards the shadow economy. In particular, dark web marketplaces (DWMs), commercial websites accessible via free software, have gained significant popularity. Here, we analyse 851,199 listings extracted from 30 DWMs between January 1, 2020 and November 16, 2020. We identify 788 listings directly related to COVID-19 products and monitor the temporal evolution of product categories including Personal Protective Equipment (PPE), medicines (e.g., hydroxyclorochine), and medical frauds. Finally, we compare trends in their temporal evolution with variations in public attention, as measured by Twitter posts and Wikipedia page visits. We reveal how the online shadow economy has evolved during the COVID-19 pandemic and highlight the importance of a continuous monitoring of DWMs, especially now that real vaccines are available and in short supply. We anticipate our analysis will be of interest both to researchers and public agencies focused on the protection of public health.
Analyzing Dynamic Code
Authors: Arceri Vincenzo , Mastroeni Isabella
Published: January 2021

Dynamic languages, such as JavaScript, employ string-to-code primitives to turn dynamically generated text into executable code at run-time. These features make standard static analysis extremely hard if not impossible, because its essential data structures, i.e., the control-flow graph and the system of recursive equations associated with the program to analyze, are themselves dynamically mutating objects. Nevertheless, assembling code at run-time by manipulating strings, such as by
eval
in JavaScript, has been always strongly discouraged, since it is often recognized that “
eval is evil
,” leading static analyzers to not consider such statements or ignoring their effects. Unfortunately, the lack of formal approaches to analyze string-to-code statements pose a perfect habitat for malicious code, that is surely evil and do not respect good practice rules, allowing them to hide malicious intents as strings to be converted to code and making static analyses blind to the real malicious aim of the code. Hence, the need to handle string-to-code statements approximating what they can execute, and therefore allowing the analysis to continue (even in the presence of dynamically generated program statements) with an acceptable degree of precision, should be clear. To reach this goal, we propose a static analysis allowing us to collect string values and to soundly over-approximate and analyze the code potentially executed by a string-to-code statement.
A Practical Tutorial for Decision Tree Induction
Authors: Hernández Víctor Adrián Sosa , Monroy Raúl , Medina-Pérez Miguel Angel , Loyola-González Octavio , Herrera Francisco
Published: January 2021

Experts from different domains have resorted to machine learning techniques to produce explainable models that support decision-making. Among existing techniques, decision trees have been useful in many application domains for classification. Decision trees can make decisions in a language that is closer to that of the experts. Many researchers have attempted to create better decision tree models by improving the components of the induction algorithm. One of the main components that have been studied and improved is the evaluation measure for candidate splits.

In this article, we introduce a tutorial that explains decision tree induction. Then, we present an experimental framework to assess the performance of 21 evaluation measures that produce different C4.5 variants considering 110 databases, two performance measures, and 10× 10-fold cross-validation. Furthermore, we compare and rank the evaluation measures by using a Bayesian statistical analysis. From our experimental results, we present the first two performance rankings in the literature of C4.5 variants. Moreover, we organize the evaluation measures into two groups according to their performance. Finally, we introduce meta-models that automatically determine the group of evaluation measures to produce a C4.5 variant for a new database and some further opportunities for decision tree models.
Designing Strong Privacy Metrics Suites Using Evolutionary Optimization
Authors: Wagner Isabel , Yevseyeva Iryna
Published: January 2021

The ability to measure privacy accurately and consistently is key in the development of new privacy protections. However, recent studies have uncovered weaknesses in existing privacy metrics, as well as weaknesses caused by the use of only a single privacy metric. Metrics suites, or combinations of privacy metrics, are a promising mechanism to alleviate these weaknesses, if we can solve two open problems: which metrics should be combined and how. In this article, we tackle the first problem, i.e., the selection of metrics for strong metrics suites, by formulating it as a knapsack optimization problem with both single and multiple objectives. Because solving this problem exactly is difficult due to the large number of combinations and many qualities/objectives that need to be evaluated for each metrics suite, we apply 16 existing evolutionary and metaheuristic optimization algorithms. We solve the optimization problem for three privacy application domains: genomic privacy, graph privacy, and vehicular communications privacy. We find that the resulting metrics suites have better properties, i.e., higher monotonicity, diversity, evenness, and shared value range, than previously proposed metrics suites.
VidCloud
Authors: Al-Abbasi Abubakr O. , Aggarwal Vaneet
Published: January 2021

As video-streaming services have expanded and improved, cloud-based video has evolved into a necessary feature of any successful business for reaching internal and external audiences. In this article, video streaming over distributed storage is considered where the video segments are encoded using an erasure code for better reliability. We consider a representative system architecture for a realistic (typical) content delivery network (CDN). Given multiple parallel streams/link between each server and the edge router, we need to determine, for each client request, the subset of servers to stream the video, as well as one of the parallel streams from each chosen server. To have this scheduling, this article proposes a two-stage probabilistic scheduling. The selection of video quality is also chosen with a certain probability distribution that is optimized in our algorithm. With these parameters, the playback time of video segments is determined by characterizing the download time of each coded chunk for each video segment. Using the playback times, a bound on the moment generating function of the stall duration is used to bound the mean stall duration. Based on this, we formulate an optimization problem to jointly optimize the convex combination of mean stall duration and average video quality for all requests, where the two-stage probabilistic scheduling, video quality selection, bandwidth split among parallel streams, and auxiliary bound parameters can be chosen. This non-convex problem is solved using an efficient iterative algorithm. Based on the offline version of our proposed algorithm, an online policy is developed where servers selection, quality, bandwidth split, and parallel streams are selected in an online manner. Experimental results show significant improvement in QoE metrics for cloud-based video as compared to the considered baselines.
Diagnosis for Reconfigurable Single-Electron Transistor Arrays with a More Generalized Defect Model
Authors: Wu Chia-Cheng , Hu Yi-Hsiang , Lin Chia-Chun , Chen Yung-Chih , Huang Juinn-Dar , Wang Chun-Yao
Published: January 2021

Singe-Electron Transistor (SET) is considered as a promising candidate of low-power devices for replacement or co-existence with Complementary Metal-Oxide-Semiconductor (CMOS) transistors/circuits. In this work, we propose a diagnosis approach for SET array under a more generalized defect model. With the more generalized defect model, the diagnosis approach will become more practical but complicated. We conducted experiments on a set of SET arrays with different dimensions and defect rates. The experimental results show that our approach only has 3.8% false-negative rate and 0.7% misjudged-category rate on average without reporting any false-positive edge when the defect rate is 4%. Therefore, the proposed diagnosis approach can diagnose the defective SET arrays and elevate the reliability of the SET arrays in the synthesis flow.
Alternative Protein Sources as Technofunctional Food Ingredients
Authors: Grossmann Lutz , Weiss Jochen
Published: January 2021

Proteins obtained from alternative sources such as plants, microorganisms, and insects have attracted considerable interest in the formulation of new food products that have a lower environmental footprint and offer means to feed a growing world population. In contrast to many established proteins, and protein fractions for which a substantial amount of knowledge has accumulated over the years, much less information is available on these emerging proteins. This article reviews the current state of knowledge on alternative proteins and their sources, highlighting gaps that currently pose obstacles to their more widespread application in the food industry. The compositional, structural, and functional properties of alternative proteins from various sources, including plants, algae, fungi, and insects, are critically reviewed. In particular, we focus on the factors associated with the creation of protein-rich functional ingredients from alternative sources. The various protein fractions in these sources are described as well as their behavior under different environmental conditions (e.g., pH, ionic strength, and temperature). The extraction approaches available to produce functional protein ingredients from these alternative sources are introduced as well as challenges associated with designing large-scale commercial processes. The key technofunctional properties of alternative proteins, such as solubility, interfacial activity, emulsification, foaming, and gelation properties, are introduced. In particular, we focus on the formation of isotropic and anisotropic structures suitablefor creating meat and dairy product analogs using various structuring techniques. Finally, selected studies on consumer acceptance and sustainability of alternative protein products are considered.
Emerging Applications of Machine Learning in Food Safety
Authors: Deng Xiangyu , Cao Shuhao , Horn Abigail L.
Published: January 2021

Food safety continues to threaten public health. Machine learning holds potential in leveraging large, emerging data sets to improve the safety of the food supply and mitigate the impact of food safety incidents. Foodborne pathogen genomes and novel data streams, including text, transactional, and trade data, have seen emerging applications enabled by a machine learning approach, such as prediction of antibiotic resistance, source attribution of pathogens, and foodborne outbreak detection and risk assessment. In this article, we provide a gentle introduction to machine learning in the context of food safety and an overview of recent developments and applications. With many of these applications still in their nascence, general and domain-specific pitfalls and challenges associated with machine learning have begun to be recognized and addressed, which are critical to prospective use and future deployment of large data sets and their associated machine learning models for food safety applications.
Deconvoluting Reversible and Irreversible Degradation Phenomena in OER Catalyst Coated Membranes Using a Modified RDE Technique
Authors: Petzoldt Philip J. , Kwan Jason Tai Hong , Bonakdarpour Arman , Wilkinson David P.
Published: January 2021

The suitability of the Thin-Film RDE (TF-RDE) technique to rigorously evaluate stability measurements for the oxygen evolution reaction (OER) was recently questioned. The main issue was the inability to deconvolute bubble blockage of catalytic active sites from catalyst dissolution using the TF-RDE technique. It is also possible that the low-loading of TF-RDE OER catalysts exacerbates the effect of bubble blockage. In this work, the modified rotating disk electrode (MRDE) is used with commercial catalyst coated membranes (CCMs) to evaluate catalyst stability. The MRDE may be better suited for stability measurements, since the CCM samples used can better avoid experimental artifacts and can explore much higher current densities than a TF-RDE. Thicker catalyst layers have good adhesion to the membrane, making experimental artifacts less pronounced in stability measurements. Three different stability protocols are used to study the effect of cycling, lower/upper potential limits, and regeneration. The protocol which induced the most irreversible degradation was the square-wave voltammetry (SWV) cycling between 0.05–2.0 VRHE. This irreversible degradation is likely the result of catalyst dissolution. The importance of differentiating between irreversible and reversible degradation is highlighted as a potential future standard for stability evaluation.
Size-Controllable Strategy of ZnO Micro/Nanorods for Electrochemical Detection of H2O2
Authors: Ahmed Md. Maruf , Zhang Kangli , Shang Yangyang , Zhao Ruihua , Liu Lu , Du Qianqian , Guo Tianyu , Du Jianping , Li Jinping
Published: January 2021

An electrochemical sensor was promoted for the rapid and efficient detection of hydrogen peroxide via the ZnO nano/microrods-based (GCE) electrode. The ZnO nano/microrods were controllable prepared by changing zinc precursor under hydrothermal condition and the sensing properties of ZnO materials were studied. The sensing performance was optimized by adjusting ZnO’s morphologies and size. The ZnO nanorods (ZNRs)-based electrode exhibits a notable sensing response toward hydrogen peroxide compared to other modified GCE. More importantly, the developed ZNRs-based sensor possesses high sensitivity of 10.8 μA mM−1 and a detection limit (LOD) of 0.28 μM. Thus, the synthesized ZNRs material is proved to be a potential material for the hydrogen peroxide detection in various fields.
Relationship between the Resistivity Profiles Obtained from the Power Law Model and the Physico-Chemical Properties of Passive Films
Authors: Marcelin S. , Zhang Z. , Ter-Ovanessian B. , Normand B.
Published: January 2021

The constant-phase-element behavior measured for passive films was analysed using the power law model. It allows to obtain the variation of the resistivity through the passive film thickness. To avoid many unknown parameters required for the model, a methodology to analyze the impedance diagrams has been described. It is illustrated with several examples. First, the resistivity profiles were obtained for a Ni-20Cr alloy immersed in solutions with different pH values to validate the proposed methodology. The dielectric properties of the passive films were discussed from the duplex character of these passive layers. It was shown that the shape of the resistivity profile could be attributed to the contribution and the thickness of the inner dense oxide and the outer hydroxide layers, respectively. Then, the second example provided information on the evolution of the behavior of the passive film formed on 316L stainless steel under irradiation.
Confocal 3D DNA Cytometry: Assessment of Required Coefficient of Variation by Computer Simulation
Authors: Ploeger Lennert S. , Beliën Jeroen A.M. , Poulin Neal M. , Grizzle William , Diest Paul J. van
Published: January 2021

Background: Confocal Laser Scanning Microscopy (CLSM) provides the opportunity to perform 3D DNA content measurements on intact cells in thick histological sections. So far, sample size has been limited by the time consuming nature of the technology. Since the power of DNA histograms to resolve different stemlines depends on both the sample size and the coefficient of variation (CV) of histogram peaks, interpretation of 3D CLSM DNA histograms might be hampered by both a small sample size and a large CV. The aim of this study was to analyze the required CV for 3D CLSM DNA histograms given a realistic sample size. Methods: By computer simulation, virtual histograms were composed for sample sizes of 20000, 10000, 5000, 1000, and 273 cells and CVs of 30, 25, 20, 15, 10 and 5%. By visual inspection, the histogram quality with respect to resolution of G0/1 and G2/M peaks of a diploid stemline was assessed. Results: As expected, the interpretability of DNA histograms deteriorated with decreasing sample sizes and higher CVs. For CVs of 15% and lower, a clearly bimodal peak pattern with well distinguishable G0/1 and G2/M peaks were still seen at a sample size of 273 cells, which is our current average sample size with 3D CLSM DNA cytometry. Conclusions: For unambiguous interpretation of DNA histograms obtained using 3D CLSM, a CV of at most 15% is tolerable at currently achievable sample sizes. To resolve smaller near diploid stemlines, a CV of 10% or better should be aimed at. With currently available 3D imaging technology, this CV is achievable.
Quality Assurance System Using Statistical Process Control: An Implementation for Image Cytometry
Authors: Chiu David , Guillaud Martial , Cox Dennis , Follen Michele , MacAulay Calum
Published: January 2021

Aims: Optical technologies have shown some promise for improving the care of cervical neoplasia. We are currently evaluating fluorescence and reflectance spectroscopy and quantitative cyto‐histopathology for cervical neoplasia screening and diagnosis. Here we describe the establishment and application of a quality assurance (QA) system for detecting system malfunctions and assessing the comparability of four image cytometers used in a multicenter clinical trial. Methods: Our QA system involves three levels of evaluation based on the periodicity and complexity of the measurements. We implemented our QA system at three image cytometers at the British Columbia Cancer Agency and one at M.D. Anderson Cancer Center. The measurements or tasks were performed daily, monthly, and semi‐annually. The current and voltage of the lamp, the calibration image characteristics, and the room temperature were checked daily. Long‐term stability over time, short‐term variability over time, and spatial response field uniformity were evaluated monthly. Camera linearity was measured semi‐annually. Control charts based on statistical process control techniques were used to detect when the system did not perform optimally. Results: Daily measurements have shown good consistency in room temperature, lamp and calibration behaviour. Monthly measurements have shown small coefficients of variation between and within the four devices. There have been greater differences between sessions than within sessions. Comparability among the four systems is reasonably good. Semi‐annual measurements have shown stable camera linearity. QA events were detected using the QA system. Multiple examples of event detection leading to correction of system malfunction are described in this report. Conclusions: QA programs are critical for ensuring data integrity and therefore for the conduct of multicenter clinical trials.
Classification of Incidental Carcinoma of the Prostate Using Learning Vector Quantization and Support Vector Machines
Authors: Mattfeldt Torsten , Trijic Danilo , Gottfried Hans‐Werner , Kestler Hans A.
Published: January 2021

The subclassification of incidental prostatic carcinoma into the categories T1a and T1b is of major prognostic and therapeutic relevance. In this paper an attempt was made to find out which properties mainly predispose to these two tumor categories, and whether it is possible to predict the category from a battery of clinical and histopathological variables using newer methods of multivariate data analysis. The incidental prostatic carcinomas of the decade 1990–99 diagnosed at our department were reexamined. Besides acquisition of routine clinical and pathological data, the tumours were scored by immunohistochemistry for proliferative activity and p53‐overexpression. Tumour vascularization (angiogenesis) and epithelial texture were investigated by quantitative stereology. Learning vector quantization (LVQ) and support vector machines (SVM) were used for the purpose of prediction of tumour category from a set of 10 input variables (age, Gleason score, preoperative PSA value, immunohistochemical scores for proliferation and p53‐overexpression, 3 stereological parameters of angiogenesis, 2 stereological parameters of epithelial texture). In a stepwise logistic regression analysis with the tumour categories T1a and T1b as dependent variables, only the Gleason score and the volume fraction of epithelial cells proved to be significant as independent predictor variables of the tumour category. Using LVQ and SVM with the information from all 10 input variables, more than 80 of the cases could be correctly predicted as T1a or T1b category with specificity, sensitivity, negative and positive predictive value from 74–92%. Using only the two significant input variables Gleason score and epithelial volume fraction, the accuracy of prediction was not worse. Thus, descriptive and quantitative texture parameters of tumour cells are of major importance for the extent of propagation in the prostate gland in incidental prostatic adenocarcinomas. Classical statistical tools and neuronal approaches led to consistent conclusions.
Prognostic Value of Adaptive Textural Features–The Effect of Standardizing Nuclear First‐Order Gray Level Statistics and Mixing Information from Nuclei Having Different Area
Authors: Nielsen Birgitte , Danielsen Håvard E.
Published: January 2021

Background: Nuclear texture analysis is a useful method to obtain quantitative information for use in prognosis of cancer. The first‐order gray level statistics of a digitized light microscopic nuclear image may be influenced by variations in the image input conditions. Therefore, we have previously standardized the nuclear gray level mean value and standard deviation. However, there is a clear relation between nuclear DNA content, area, first‐order statistics, and texture. For nuclei with approximately the same DNA content, the mean gray level increases with an increasing nuclear area. The aims of the present methodical work were to study: (1) whether the prognostic value of adaptive textural features varies with nuclear area, and (2) the effect of standardizing nuclear first‐order statistics. Methods: Nuclei from 134 cases of ovarian cancer were grouped into intervals according to nuclear area. Adaptive features were extracted from two different image sets, i.e., standardized and non‐standardized nuclear images. Results: The prognostic value of adaptive textural features varied strongly with nuclear area. A standardization of the first‐order statistics significantly reduced this prognostic information. Several single features discriminated the two classes of cancer with a correct classification rate of 70%. Conclusion: Nuclei having an area between 2000–4999 pixels contained most of the class distance information between the good and poor prognosis classes of cancer. By considering the relation between nuclear area and texture, we avoided a loss of information caused by standardizing the first‐order statistics and mixing data from cells having different nuclear area.
The Expression and Action of Decay‐Accelerating Factor (CD55) in Human Malignancies and Cancer Therapy
Authors: Mikesch Jan-Henrik , Schier Kathrin , Roetger Antje , Simon Ronald , Buerger Horst , Brandt Burkhard
Published: January 2021

Decay‐accelerating factor (DAF, CD55) is physiologically acting as an inhibitor of the complement system, but is also broadly expressed in malignant tumours. Here DAF seems to exert different functions beyond its immunological role such as e.g. promotion of tumorigenesis, decrease of complement mediated tumor cell lysis, autocrine loops for cell rescue and evasion of apoptosis, neoangiogenesis, invasiveness, cell motility, and metastasis via oncogenic tyrosine kinase pathways and specific seven‐span transmembrane receptors (CD97) binding. Therefore, DAF has already become a target for therapy. In this paper we review the role of DAF in human malignancies as described in different basic, diagnostic and experimental therapeutic studies.
Ligands of the Mitochondrial 18 kDa Translocator Protein Attenuate Apoptosis of Human Glioblastoma Cells Exposed to Erucylphosphohomocholine
Authors: Kugler Wilfried , Veenman Leo , Shandalov Yulia , Leschiner Svetlana , Spanier Ilana , Lakomek Max , Gavish Moshe
Published: January 2021

Background: We have previously shown that the anti-neoplastic agent erucylphosphohomocholine (ErPC3) requires the mitochondrial 18 kDa Translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor (PBR), to induce cell death via the mitochondrial apoptosis pathway.

Methods: With the aid of the dye JC-1 and cyclosporin A, applied to glioblastoma cells, we now investigated the significance of opening of the mitochondrial permeability transition pore (MPTP) for ErPC3-induced apoptosis in interaction with the TSPO ligands, PK 11195 and Ro5 4864. Furthermore, we measured cytochrome c release, and caspase-9 and -3 activation in this paradigm.

Results: The human glioblastoma cell lines, U87MG, A172 and U118MG express the MPTP-associated TSPO, voltage-dependent anion channel and adenine nucleotide transporter. Indeed, ErPC3-induced apoptosis was inhibited by the MPTP blocker cyclosporin A and by PK 11195 and Ro5 4864 in a concentration-dependent manner. Furthermore, PK 11195 and Ro5 4864 inhibited collapse of the mitochondrial membrane potential, cytochrome c release, and caspase-9 and -3 activation caused by ErPC3 treatment.

Conclusions: This study shows that PK 11195 and Ro5 4864 inhibit the pro-apoptotic function of ErPC3 by blocking its capacity to cause a collapse of the mitochondrial membrane potential. Thus, the TSPO may serve to open the MPTP in response to anti-cancer drugs such as ErPC3.
Alterations in AP‐1 and AP‐1 Regulatory Genes during HPV‐Induced Carcinogenesis
Authors: de Wilde Jillian , De-Castro Arce Johanna , Snijders Peter J. F. , Meijer Chris J. L. M. , Rösl Frank , Steenbergen Renske D. M.
Published: January 2021

Background: Previous studies demonstrated a functional involvement of the AP‐1 transcription factor in HPV‐induced cervical carcinogenesis. Here, we aimed to obtain further insight in expression alterations of AP‐1 family members during HPV‐mediated transformation and their relationship to potential regulatory (Notch1, Net) and target (CADM1) genes.

Methods: mRNA expression levels of c‐Jun, JunB, junD, c‐Fos, FosB, Fra‐1, Fra‐2, Notch1, Net and CADM1 were determined by quantitative RT‐PCR in primary keratinocytes (n=5), early (n=4) and late (n=4) passages of non‐tumorigenic HPV‐immortalized keratinocytes and in tumorigenic cervical cancer cell lines (n=7). In a subset of cell lines protein expression and AP‐1 complex composition was determined.

Results: Starting in immortal stages c‐Fos, Fra‐2 and JunB expression became up regulated towards tumorigenicity, whereas Fra‐1, c‐Jun, Notch1, Net and CADM1 became down regulated. The onset of deregulated expression varied amongst the AP‐1 members and was not directly related to altered Notch1, Net or CADM1 expression. Nevertheless, a shift in AP‐1 complex composition from Fra‐1/c‐Jun to c‐Fos/c‐Jun heterodimers was only observed in tumorigenic cells.

Conclusion: HPV‐mediated transformation is associated with altered AP‐1, Notch1, Net and CADM1 transcription. Whereas the onset of deregulated expression of various AP‐1 family members became already manifest during the immortal state, a shift in AP‐1 complex composition appeared a rather late event associated with tumorigenicity.
Altered Cellular Distribution and Sub-Cellular Sorting of Doppel (Dpl) Protein in Human Astrocytoma Cell Lines
Authors: Sbalchiero Elena , Azzalin Alberto , Palumbo Silvia , Barbieri Giulia , Arias Agustina , Simonelli Luca , Ferretti Luca , Comincini Sergio
Published: January 2021

Doppel, a prion-like protein, is a GPI-membrane anchored protein generally not expressed in the Central Nervous System (CNS) of different mammalian species, including human. Nevertheless, in astrocytomas, a particular kind of glial tumors, the doppel encoding gene (PRND) is over-expressed and the corresponding protein product (Dpl) is ectopically localized in the cytoplasm of the tumor cells. In this study we have analysed the sub-cellular localization of Dpl using double-immunofluorescence staining and confocal microscopy examinations in two astrocytoma-derived human cell lines (IPDDC-A2 and D384-MG). Our results confirmed that Dpl is localized in the cytoplasm of the astrocytoma cells and indicated that it is mostly associated with Lamp-1 and Limp-2 positive lysosomal vesicles and, marginally, to the Golgi apparatus and other cellular organelles. Noticeably, none of the examined tumor cells showed a membrane-Dpl localization. The membrane-associated Dpl expression was restored after the transfection of the astrocytoma cells with mutated Dpl-expression vectors in its glycosylation sites. Additionally, Dpl showed altered expression and traffic using the acidotropic agent ammonium chloride, leading to the accumulation of Dpl in nascent exocytic vesicles. Altogether, these results indicated that in the astrocytic tumor cells Dpl has an altered biosynthetic trafficking, likely derived from abnormal post-translational processes: these modifications do not permit the localization of Dpl in correspondence of the plasma membrane and lead to its intracellular accumulation in the lysosomes. In these proteolytic compartments, the astrocytic tumor cells might provide to the degradation of the excess of a potentially cytotoxic Dpl product.