bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Mechanical Performance of Improved Low Vibration Track and Its Feasibility Analysis for Heavy-Haul Railway Applications
Authors: Zeng Zhiping , Peng Guangzhao , Guo Wuji , Huang Xiangdong , Wang Weidong , Hu Ji , Li Shiye , Shuaibu Abdulmumin Ahmed , Yuan Yu , Du Xianggang
Published: November 2021

With the gradual increase of the cargo weight of heavy-haul trains, the traditional ballasted track with the accumulation of stone and ballast has been unable to meet its structural safety requirements. From the comparison of the three common ballastless tracks in China, it can be seen that the low-vibration track (LVT) has the advantages of reasonable structure, low cost, and easy maintenance. Therefore, the design and research of heavy-haul railways are focused on, and it is urgent to study the applicability of LVT in heavy-haul railways. Method: By improving the slope of the short side of the LVT support block, the support block has a better load bearing capacity, so as to achieve the purpose of bearing a larger axle load. Through 1:1 full-scale model test and finite element simulation, the static mechanical properties of Improved LVT (ILVT) and Traditional LVT (TLVT) are compared and analyzed. Result: Compared with TLVT, ILVT has smaller vertical displacement and track gauge changes when subjected to the same load. The proven and reliable finite element model also shows that ILVT’s load sharing is less affected. In the case of achieving the same deformation, ILVT can withstand greater vertical and lateral loads. Conclusions: Compared with the TLVT, the ILVT design can reduce the vertical displacement of the rail and the supporting block, better control the track subsidence, and improve the driving safety of the LVT. At the same time, ILVT improves the anti-overturning ability of the rail and support block under lateral load, reduces the expansion of the gauge and the lateral spacing of the support block, and improves the stability of the track structure. ILVT can also be considered for the weight of 40t and other large axle load, and has broad application prospects.
An Improved GPR Method Based on BP and RPCA for Tunnel Lining Defects Detection and Its Application in Qiyue Mountain Tunnel, China
Authors: Li Dongli , Yan Echuan
Published: November 2021

Tunnel lining defects are one of the most common problems that tunnels experience during operation, and they can pose severe safety risks. The most popular nondestructive testing method for detecting tunnel lining defects is ground penetrating radar (GPR), one of the basic geophysical applications. However, detection responses might differ significantly from the real shape of tunnel lining defects, making it challenging to identify and interpret. When data quality is poor, interpretation and identification become more challenging, resulting in a high cost of tunnel repairs. The improved back projection (BP) imaging and robust principal component analysis (RPCA) are used in this work to offer a GPR data processing method. Even in the event of poor data quality, our method could recover GPR responses, allowing the shapes and locations of tunnel lining flaws to be clearly depicted. With BP imaging, this approach recovers the tunnel defects’ responses to better forms and positions, and with RPCA, it further isolates the target imaging from clutters. Several synthetic data demonstrate that the approach presented in this work may successfully repair and extract the positions and forms of lining defects, making them easier to identify and comprehend. Furthermore, our technique was used to GPR data gathered from the Qiyue Mountain Tunnel in China, yielding more accurate findings than the traditional method, which was validated by the actual scenario to illustrate the efficiency of our method on real data.
Combining the Advantages of Different Processing Solutions Using a Novel Motion Processing Approach
Authors: Holowenko Olaf , Troll Clemens , Ihlenfeldt Steffen , Majschak Jens-Peter
Published: November 2021

In processing machines, technological tasks are implemented using suitable processing solutions. Those processing solutions can in turn have very different characteristics and specific advantages and disadvantages, e.g., concerning sensitivity to changing operating speed. In state-of-the-art processing machine controls, executing one single processing solution is supported. The execution of various processing solutions together and the combination of their advantages is currently not supported at all. In this article, a motion control approach is discussed that allows combining seemingly incompatible process solutions for a given technological task into a hybrid process solution, using the example of processing machines. The objective of this approach is to increase the achievable process window of the machine in terms of operating speed. It is shown that combining different process solutions can merge their advantages and compensate for their disadvantages. The article brings together the lessons learned from previous work in a new application to exploit advantages and compensate for disadvantages.
Qualitative and Quantitative Comparison of Liquid–Liquid Phase Extraction Using Ethyl Acetate and Liquid–Solid Phase Extraction Using Poly-Benzyl-Resin for Natural Products
Authors: Schneider Yannik K. , Jørgensen Solveig M. , Andersen Jeanette Hammer , Hansen Espen H.
Published: November 2021

A key step in the process of isolating microbial natural products is the preparation of an extract from a culture. This step determines which molecules will be available for detection in the subsequent chemical and biological analysis of a biodiscovery pipeline. In the present study we wanted to document potential differences in performance between liquid–liquid extraction using ethyl acetate and liquid–solid extraction using a poly-benzyl-resin. For the comparison of the two extraction protocols, we spiked a culture of Flavobacterium sp. with a diverse selection of natural products of microbial and plant origin to investigate whether the methods were comparable with respect to selectivity. We also investigated the efficiency of the two extraction methods quantitatively, using water spiked with a selection of natural products, and studied the quantitative effect of different pH levels of the aqueous solutions on the extraction yields of the two methods. The same compounds were extracted by the two methods, but the solid-phase extract contained more media components compared with the liquid-phase extract. Quantitatively, the two extraction methods varied in their recovery rates. We conclude that practical aspects could be more important when selecting one of the extraction protocols, as their efficiencies in extracting specific compounds were quite similar.
Machine-Learning-Based Android Malware Family Classification Using Built-In and Custom Permissions
Authors: Kim Minki , Kim Daehan , Hwang Changha , Cho Seongje , Han Sangchul , Park Minkyu
Published: November 2021

Malware family classification is grouping malware samples that have the same or similar characteristics into the same family. It plays a crucial role in understanding notable malicious patterns and recovering from malware infections. Although many machine learning approaches have been devised for this problem, there are still several open questions including, “Which features, classifiers, and evaluation metrics are better for malware familial classification”? In this paper, we propose a machine learning approach to Android malware family classification using built-in and custom permissions. Each Android app must declare proper permissions to access restricted resources or to perform restricted actions. Permission declaration is an efficient and obfuscation-resilient feature for malware analysis. We developed a malware family classification technique using permissions and conducted extensive experiments with several classifiers on a well-known dataset, DREBIN. We then evaluated the classifiers in terms of four metrics: macrolevel F1-score, accuracy, balanced accuracy (BAC), and the Matthews correlation coefficient (MCC). BAC and the MCC are known to be appropriate for evaluating imbalanced data classification. Our experimental results showed that: (i) custom permissions had a positive impact on classification performance; (ii) even when the same classifier and the same feature information were used, there was a difference up to 3.67% between accuracy and BAC; (iii) LightGBM and AdaBoost performed better than other classifiers we considered.
Solid Lipid Nanoparticles as Carriers for the Synthetic Opioid LP2: Characterization and In Vitro Release
Authors: Spadaro Angelo , Pasquinucci Lorella , Lorenti Miriam , Santagati Ludovica Maria , Sarpietro Maria Grazia , Turnaturi Rita , Parenti Carmela , Montenegro Lucia
Published: November 2021

A synthetic dual-target mu opioid peptide receptor/delta opioid peptide receptor anti-nociceptive ligand, named LP2, has emerged as a promising candidate for the management of acute and/or persistent pain, but its lipophilicity limits further developments as a therapeutic agent. In this work, to allow designing aqueous formulations of LP2 for parenteral administration, solid lipid nanoparticles (SLNs) were investigated as LP2 nanocarriers. LP2-loaded SLNs were prepared by the phase-inversion temperature method, showing good technological properties (small mean particle, size, low polydispersity index, good stability). As LP2 was a diastereoisomeric mixture of 2R/2S-LP2, an HPLC method was developed to identify and quantify each diastereoisomer, and this method was used to assess LP2 in vitro release from SLNs. The developed method, based on reverse-phase chromatography using an isocratic mobile phase consisting of 50% methanol and 50% triethanolamine at 0.3% (pH = 3 with trifluoroacetic acid), allowed efficient separation of 2R- and 2S-LP2 peaks and reliable quantification with intra- and inter-day precision and accuracy within the acceptability limit, expressed as relative standard deviation set at ≤15%. The results of this study suggest that the incorporation of LP2 into SLNs could be a promising strategy to design suitable formulations for further pharmacological studies involving LP2.
Optimization Analysis of Excavation Procedure Design of Underground Powerhouses under High In Situ Stress in China
Authors: Liu Xiao , Yan Peng , Chen Ming , Luo Sheng , Lu Ang , Lu Wenbo , Wang Gaohui , Huang Shuling
Published: November 2021

To recommend the excavation procedures and design parameters for underground powerhouses, excavation procedures of fifty-one underground powerhouses in China were summarized and analyzed based on in situ stress conditions. Firstly, the complex stress environment in China was introduced and fifty-one underground powerhouses with their engineering scale, size, lithology, rock classification and in situ stress level were listed in detail. Subsequently, to evaluate the influence of in situ stress levels on excavation procedure design, the correlation between excavation procedures and in situ stress level in three main excavation zones were analyzed accordingly. Moreover, to provide the excavation design recommendations, the strength–stress ratio (SSR) was promoted to analyze and recommend the design parameters, and the blasting excavation design based on the stress transient unloading control was also supplemented. The results show that excavation procedures have different priorities under different in situ stress levels, and the design parameters show an obvious relationship with in situ stress levels. Moreover, the excavation procedure parameters are suggested to adjust accordingly under different SSR. The discussion of influencing factors and specification ensures its rationality and accuracy. It is believed that the summary and recommendations can provide a good reference for excavation procedure optimization of underground powerhouse under high in situ stress.
A Study of Current Controlled Discharge in a Nitrogen Filled Tube
Authors: Nevrkla Michal , Hubner Jakub , Sisma Jiri , Vrba Pavel , Vrbova Miroslava , Bobrova Nadezhda , Sasorov Pavel , Jancarek Alexandr
Published: November 2021

Time dependencies of the electrical resistance and electron density evolution in the discharge in a tube, with nitrogen at different pressures, with a diameter of 9.2mm and a length of 10cm were studied. A current pulse with an amplitude of 500A and duration of 10μs has created the discharge in the tube. Instantaneous electron densities are estimated from the interference pattern in Mach–Zehnder interferometer using femtosecond Ti: sapphire laser beam. Laboratory results are compared with results of computer modelling by MHD computer codes NPINCH and ZSTAR. Time development of the discharge resistance according to experiment is measured and evaluated. Minimum measurable value of the electron density in the experiment is determined as 2×1015cm−3.
Effectiveness of Prone Positioning in Patients with COVID-19-Related Acute Respiratory Distress Syndrome Undergoing Invasive Mechanical Ventilation
Authors: Astasio-Picado Álvaro , Sánchez-Sánchez María del Rocío
Published: November 2021

The prone position is a non-invasive technique resulting from the mobilization of the patient, where the person is lying horizontally face down. This technique has been used since the 1970s, but it has gained great relevance in the last year owing to the COVID-19 pandemic with the use of invasive mechanical ventilation. Objectives: To evaluate the effectiveness of the prone position in patients with acute respiratory distress syndrome as a consequence of the COVID-19 disease who are mechanically ventilated and admitted to the intensive care unit. To demonstrate the nursing care carried out and to identify the respiratory benefits of the prone position in this type of patient. Data sources, study eligibility criteria: The search for articles was carried out from January 2018 to June 2021, in five databases (Pubmed, Google Scholar, Scielo, Dialnet, and WOS), based on the clinical question, using the keywords derived from the DeCS and MeSH thesauri, combined with the Boolean operators “AND”, “NOT”, and “OR”. The search was limited to publications from the last 6 years, in English. Results: After applying the selection criteria and evaluating the quality of the methodology, 12.14% (n = 21) of the 173 results were included with filters: 3 bibliographic reviews, 1 narrative review, 2 systematic review, 7 descriptive (4 series of cases and 3 of cross section), and 8 analytical (6 of cohorts and 2 of cases and controls). Conclusions and implications of key findings: The prone position in adults with acute respiratory distress syndrome improves oxygenation, in conjunction with invasive mechanical ventilation, from the second cycle and in prolonged pronation episodes. This technique improves oxygenation by increasing alveolar recruitment and inspiratory capacity in the dorsal pulmonary areas.
Elastic Scattering of Slow Electrons by Noble Gases—The Effective Range Theory and the Rigid Sphere Model
Authors: Fedus Kamil
Published: November 2021

We report on an extensive semi-empirical analysis of scattering cross-sections for electron elastic collision with noble gases via the Markov Chain Monte Carlo-Modified Effective Range Theory (MCMC−MERT). In this approach, the contribution of the long-range polarization potential (∼r−4) to the scattering phase shifts is precisely expressed, while the effect of the complex short-range interaction is modeled by simple quadratic expression (the so-called effective range expansion with several adjustable parameters). Additionally, we test a simple potential model of a rigid sphere combined with r−4 interaction. Both models, the MERT and the rigid sphere are based on the analytical properties of Mathieu functions, i.e., the solutions of radial Schrödinger equation with pure polarization potential. However, in contrast to MERT, the rigid sphere model depends entirely upon one adjustable parameter—the radius of a hard-core. The model’s validity is assessed by a comparative study against numerous experimental cross-sections and theoretical phase shifts. We show that this simple approach can successfully describe the electron elastic collisions with helium and neon for energies below 1 eV. The purpose of the present analysis is to give insight into the relations between the parameters of both models (that translate into the cross-sections in the very low energy range) and some “macroscopic” features of atoms such as the polarizability and atomic “radii”.
A Relation-Theoretic Formulation of Browder–Göhde Fixed Point Theorem
Authors: Alam Aftab , Imdad Mohammad , Asim Mohammad , Sessa Salvatore
Published: November 2021

In this paper, we introduce the concept of R-nonexpansive self-mappings defined on a suitable subset K of a Banach space, wherein R stands for a transitive binary relation on K, and utilize the same to prove a relation-theoretic variant of classical Browder–Göhde fixed point theorem. As consequences of our newly proved results, we are able to derive several core fixed-point theorems existing in the literature.
Local and Global Stability of Certain Mixed Monotone Fractional Second Order Difference Equation with Quadratic Terms
Authors: Garić-Demirović Mirela , Hrustić Sabina , Nurkanović Zehra
Published: November 2021

This paper investigates the local and global character of the unique positive equilibrium of a mixed monotone fractional second-order difference equation with quadratic terms. The corresponding associated map of the equation decreases in the first variable, and it can be either decreasing or increasing in the second variable depending on the corresponding parametric values. We use the theory of monotone maps to study global dynamics. For local stability, we use the center manifold theory in the case of the non-hyperbolic equilibrium point. We show that the observed equation exhibits three types of global behavior characterized by the existence of the unique positive equilibrium, which can be locally stable, non-hyperbolic when there also exist infinitely many non-hyperbolic and stable minimal period-two solutions, and a saddle. Numerical simulations are carried out to better illustrate the results.
Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium
Authors: Dworakowska Beata , Gawlak Maciej , Nurowska Ewa
Published: November 2021

TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity—from very low to very high—independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity. Single-channel patch clamp recordings were performed on freshly dissociated pyramidal neurons of rat prefrontal cortexes in both the cell-attached and inside-out configurations. To evaluate the role of endogenous stimulants, the activity of the channels was recorded in the presence of a PI(4,5)P2 analogue (PI(4,5)P2DiC8) and Ca2+. Our research revealed that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics. The observation that calcium participates in the activation of TREK-2-like channels is a new finding. We showed that PI(4,5)P2-dependent TREK-2 activity occurs when the conditions for PI(4,5)P2/Ca2+ nanocluster formation are met. We present a possible model explaining the mechanism of calcium action.
The First WHO International Standard for Harmonizing the Biological Activity of Bevacizumab
Authors: Jia Haiyan , Harikumar Parvathy , Atkinson Eleanor , Rigsby Peter , Wadhwa Meenu
Published: November 2021

Several Bevacizumab products are approved for clinical use, with many others in late-stage clinical development worldwide. To aid the harmonization of potency assessment across different Bevacizumab products, the first World Health Organization (WHO) International Standard (IS) for Bevacizumab has been developed. Two preparations of a Bevacizumab candidate and comparator were assessed for their ability to neutralize and bind vascular endothelial growth factor (VEGF) using different bioassays and binding assays in an international collaborative study. Relative potency estimates were similar across different assays for the comparator or the duplicate-coded candidate sample. Variability in relative potency estimates was reduced when the candidate standard was used for calculation compared with various in-house reference standards, enabling harmonization in bioactivity evaluations. The results demonstrated that the candidate standard is suitable to serve as an IS for Bevacizumab, with assigned unitages for VEGF neutralization and VEGF binding activity. This standard coded 18/210 was established by the WHO Expert Committee on Biological Standardization, which is intended to support the calibration of secondary standards for product development and lifecycle management. The availability of IS 18/210 will help facilitate the global harmonization of potency evaluation to ensure patient access to Bevacizumab products with consistent safety, quality and efficacy.
Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group
Authors: Boyaci Ceren , Sun Wenwen , Robertson Stephanie , Acs Balazs , Hartman Johan
Published: November 2021

Ki67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in Breast Cancer Working Group (IKWG) for Ki67 scoring and to evaluate the prognostic potential of this platform in an independent cohort. Four algorithms were independently built by four pathologists based on our study cohort using an open-source digital image analysis (DIA) platform (QuPath) following the detailed guideline of the IKWG. The algorithms were applied on an ER+ breast cancer study cohort of 157 patients with 15 years of follow-up. The reference Ki67 score was obtained by a DIA algorithm trained on a subset of the study cohort. Intraclass correlation coefficient (ICC) was used to measure reproducibility. High interobserver reliability was reached with an ICC of 0.938 (CI: 0.920–0.952) among the algorithms and the reference standard. Comparing each machine-read score against relapse-free survival, the hazard ratios were similar (2.593–4.165) and showed independent prognostic potential (p ≤ 0.018, for all comparisons). In conclusion, we demonstrate high reproducibility and independent prognostic potential using the IKWG DIA instructions to score Ki67 in breast cancer. A prospective study is needed to assess the clinical utility of the IKWG DIA Ki67 instructions.
Peripheral Nerve Stimulation for Treatment of Headaches: An Evidence-Based Review
Authors: Zhou Steven , Hussain Nasir , Abd-Elsayed Alaa , Boulos Racha , Hakim Mohammed , Gupta Mayank , Weaver Tristan
Published: November 2021

Headaches are one of the most common medical complaints worldwide, and treatment is often made difficult because of misclassification. Peripheral nerve stimulation has emerged as a novel treatment for the treatment of intractable headaches in recent years. While high-quality evidence does exist regarding its use, efficacy is generally limited to specific nerves and headache types. While much research remains to bring this technology to the mainstream, clinicians are increasingly able to provide safe yet efficacious pain control.
Voltammetric Immunosensor to Track a Major Peanut Allergen (Ara h 1) in Food Products Employing Quantum Dot Labels
Authors: Freitas Maria , Nouws Henri P. A. , Delerue-Matos Cristina
Published: November 2021

Tracking unreported allergens in commercial foods can avoid acute allergic reactions. A 2-step electrochemical immunosensor was developed for the analysis of the peanut allergen Ara h 1 in a 1-h assay (<15 min hands-on time). Bare screen-printed carbon electrodes (SPCE) were used as transducers and monoclonal capture and detection antibodies were applied in a sandwich-type immunoassay. The short assay time was achieved by previously combining the target analyte and the detection antibody. Core/shell CdSe@ZnS Quantum Dots were used as electroactive label for the detection of the immunological interaction by differential pulse anodic stripping voltammetry. A linear range between 25 and 1000 ng·mL−1 (LOD = 3.5 ng·mL−1), an adequate precision of the method (Vx0 ≈ 6%), and a sensitivity of 23.0 nA·mL·ng−1·cm−2 were achieved. The immunosensor was able to detect Ara h 1 in a spiked allergen-free product down to 0.05% (m/m) of peanut. Commercial organic farming cookies and cereal and protein bars were tested to track and quantify Ara h 1. The results were validated by comparison with an ELISA kit.
Enhanced Molecular Infrared Spectroscopy Employing Bilayer Graphene Acoustic Plasmon Resonator
Authors: Wen Chunchao , Luo Jie , Xu Wei , Zhu Zhihong , Qin Shiqiao , Zhang Jianfa
Published: November 2021

Graphene plasmon resonators with the ability to support plasmonic resonances in the infrared region make them a promising platform for plasmon-enhanced spectroscopy techniques. Here we propose a resonant graphene plasmonic system for infrared spectroscopy sensing that consists of continuous graphene and graphene ribbons separated by a nanometric gap. Such a bilayer graphene resonator can support acoustic graphene plasmons (AGPs) that provide ultraconfined electromagnetic fields and strong field enhancement inside the nano-gap. This allows us to selectively enhance the infrared absorption of protein molecules and precisely resolve the molecular structural information by sweeping graphene Fermi energy. Compared to the conventional graphene plasmonic sensors, the proposed bilayer AGP sensor provides better sensitivity and improvement of molecular vibrational fingerprints of nanoscale analyte samples. Our work provides a novel avenue for enhanced infrared spectroscopy sensing with ultrasmall volumes of molecules.
All-Optical Switching Demonstrated with Photoactive Yellow Protein Films
Authors: Petrovszki Dániel , Krekic Szilvia , Valkai Sándor , Heiner Zsuzsanna , Dér András
Published: November 2021

Integrated optics (IO) is a field of photonics which focuses on manufacturing circuits similar to those in integrated electronics, but that work on an optical basis to establish means of faster data transfer and processing. Currently, the biggest task in IO is finding or manufacturing materials with the proper nonlinear optical characteristics to implement as active components in IO circuits. Using biological materials in IO has recently been proposed, the first material to be investigated for this purpose being the protein bacteriorhodopsin; however, since then, other proteins have also been considered, such as the photoactive yellow protein (PYP). In our current work, we directly demonstrate the all-optical switching capabilities of PYP films combined with an IO Mach–Zehnder interferometer (MZI) for the first time. By exploiting photoreactions in the reaction cycle of PYP, we also show how a combination of exciting light beams can introduce an extra degree of freedom to control the operation of the device. Based on our results, we discuss how the special advantages of PYP can be utilized in future IO applications.
The Impact of Reassurance on Musculoskeletal (MSK) Pain: A Qualitative Review
Authors: Cheung Lok , Soundy Andrew
Published: November 2021

Background: The reassurance provided during patient-therapist interactions is significantly associated with psychosocial outcomes, including fear and increased confidence. Currently, there are no available reviews that discuss the impact of reassurance for patients with musculoskeletal (MSK) pain. The aim of the present review was to qualitatively synthesize themes around reassurance mechanisms, and the impact during the interaction between patients with MSK pain and therapists. A systematic search strategy was undertaken. Studies were included if they were qualitative or mixed methods studies, examining the patient-therapist consultation, in any MSK clinical setting, with any health care professional, for adult patients with acute to chronic MSK pain. A thematic synthesis was conducted and supported by a particular assessment using CERQual. Results: Twenty-four studies were included (451 patients). Certain themes that related to both positive and negative outcomes of reassurance were identified as well as themes that illustrate the mechanisms causative of the outcomes. Using CerQual, we identified the most supported outcomes. Conclusions: Effective reassurance includes affectionate interactions such as therapeutic relationship building and interpersonal skills, an individualized patient-centered approach, education and the provision of self-management strategies. It should be noted that some interactions that use pathoanatomic models led patients to misinterpret the information provided, this created feelings of fear.
Physical Tests of Alternative Connections of Different High Roof Purlins Regarding Upward Loading
Authors: Rosmanit Miroslav , Pařenica Přemysl , Sucharda Oldřich , Lehner Petr
Published: November 2021

Thin-walled cold-rolled sections are used in the construction industry, especially in the roofing of large-span halls. The load-bearing capacity of a thin-walled structure depends to a large extent on the load-bearing capacity of the details at the point of attachment to the structure and the interconnection of the individual thin-walled elements. Therefore, in the case of thin-walled structures, it is necessary to use additional structural elements such as local reinforcement, stabilising elements, supports, and other structural measures such as the doubling of profiles. This paper focused on the behaviour of tall Z300 and Z350 mm thin-walled trusses at the connection to the superstructure regarding upward loading (e.g., wind suction and so on). Two section thicknesses, 1.89 mm and 2.85 mm, were experimentally analysed. Furthermore, two types of connections were prepared, more precisely without and with a reinforced buckle. The experiments aimed to investigate the behaviour and load-carrying capacity of the detail of the roof truss connections to the supporting structure. The resulting load capacity values were compared with normative approaches. Analyses of the details of the bolt in the connection are also presented. The paper presents a practical evaluation of the physical test on real structural members.
Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT
Authors: Álvarez-Torres María del Mar , Fuster-García Elies , Balaña Carmen , Puig Josep , García-Gómez Juan M.
Published: November 2021

In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.
Role of Cardiac Biomarkers in Cancer Patients
Authors: Semeraro Gennaro Carmine , Cipolla Carlo Maria , Cardinale Daniela Maria
Published: November 2021

In patients with cancer—and especially some specific subtypes—the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily accessible tools for prediction, early diagnosis, monitoring, or prognosis of various forms of cancer-related cardiac diseases. However, their clinical usefulness was not always clearly demonstrated in every area of cardioncology. For the identification of anthracycline related cardiotoxicity in the very early stages troponins proved to be more efficient detectors than imaging methods. Nevertheless, the lack of a standardized dosage methodology and of cardiotoxicity specific thresholds, do not yet allow to outline the precise way to employ them in clinical routine and to incorporate them into appropriate diagnostic or managing algorithms. Cardiac biomarkers proved also effective in patients with primary cardiac amyloidosis, in which both troponins and natriuretic peptides were able to predict adverse outcome, and carcinoid heart disease, where a precise diagnostic cut-off for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was identified to screen patients with valvular involvement. Likewise, NT-proBNP proved to be an excellent predictor of postoperative atrial fibrillation (POAF). On the contrary, evidence is still not sufficient to promote the routine use of cardiac biomarkers to early diagnose myocarditis due to immune check points inhibitors (ICIs), radiotherapy induced cardiotoxicity and cardiac complications related to androgenetic deprivation. In this review we present all the evidence gathered so far regarding the usefulness and limitations of these relatively inexpensive diagnostic tools in the field of cardio-oncology.
Locus-Specific DNA Methylation Editing in Melanoma Cell Lines Using a CRISPR-Based System
Authors: Smith Jim , Banerjee Rakesh , Waly Reema , Urbano Arthur , Gimenez Gregory , Day Robert , Eccles Michael R. , Weeks Robert J. , Chatterjee Aniruddha
Published: November 2021

DNA methylation is a key epigenetic modification implicated in the pathogenesis of numerous human diseases, including cancer development and metastasis. Gene promoter methylation changes are widely associated with transcriptional deregulation and disease progression. The advent of CRISPR-based technologies has provided a powerful toolkit for locus-specific manipulation of the epigenome. Here, we describe a comprehensive global workflow for the design and application of a dCas9-SunTag-based tool for editing the DNA methylation locus in human melanoma cells alongside protocols for downstream techniques used to evaluate subsequent methylation and gene expression changes in methylation-edited cells. Using transient system delivery, we demonstrate both highly efficacious methylation and demethylation of the EBF3 promoter, which is a putative epigenetic driver of melanoma metastasis, achieving up to a 304.00% gain of methylation and 99.99% relative demethylation, respectively. Furthermore, we employ a novel, targeted screening approach to confirm the minimal off-target activity and high on-target specificity of our designed guide RNA within our target locus.
Use of Diagnostic Criteria from ACR and EU-TIRADS Systems to Improve the Performance of Cytology in Thyroid Nodule Triage
Authors: Seminati Davide , Capitoli Giulia , Leni Davide , Fior Davide , Vacirca Francesco , Di Bella Camillo , Galimberti Stefania , L’Imperio Vincenzo , Pagni Fabio
Published: November 2021

Objective: The American College of Radiology (ACR) and the European Thyroid Association (EU) have proposed two scoring systems for thyroid nodule classification. Here, we compared the ability of the two systems in triaging thyroid nodules for fine-needle aspiration (FNA) and tested the putative role of an approach that combines ultrasound features and cytology for the detection of malignant nodules. Design and Methods: The scores obtained with the ACR and EU Thyroid Imaging Reporting and Data Systems (TIRADS) from a prospective series of 480 thyroid nodules acquired from 435 subjects were compared to assess their performances in FNA triaging on the final cytological diagnosis. The US features that showed the highest contribution in discriminating benign nodules from malignancies were combined with cytology to improve its diagnostic performance. Results: FNA was recommended on 46.5% and 51.9% of the nodules using the ACR and EU-TIRADS scores, respectively. The ACR system demonstrated a higher specificity as compared to the EU-TIRADS (59.0% vs. 52.4%, p = 0.0012) in predicting ≥ TIR3A/III (SIAPEC/Bethesda) nodules. Moreover, specific radiological features (i.e., echogenic foci and margins), combined with the cytological classes improved the specificity (97.5% vs. 91%, p < 0.0001) and positive predictive values (77.5% vs. 50.7%, p < 0.0001) compared to cytology alone, especially in the setting of indeterminate nodules (TIR3A/III and TIR3B/IV), maintaining an excellent sensitivity and negative predictive value. Conclusions: The ACR-TIRADS system showed a higher specificity compared to the EU-TIRADS in triaging thyroid nodules. The use of specific radiological features improved the diagnostic ability of cytology.
Single-Cell Proteomic Analysis Dissects the Complexity of Tumor Microenvironment in Muscle Invasive Bladder Cancer
Authors: Feng Chao , Wang Xi , Tao Yuting , Xie Yuanliang , Lai Zhiyong , Li Zhijian , Hu Jiaxin , Tang Shaomei , Pan Lixin , He Liangyu , Wang Qiuyan , Li Tianyu , Mo Zengnan
Published: November 2021

Muscle invasive bladder cancer (MIBC) is a malignancy with considerable heterogeneity. The MIBC tumor microenvironment (TME) is highly complex, comprising diverse phenotypes and spatial architectures. The complexity of the MIBC TME must be characterized to provide potential targets for precision therapy. Herein, an integrated combination of mass cytometry and imaging mass cytometry was used to analyze tumor cells, immune cells, and TME spatial characteristics of 44 MIBC patients. We detected tumor and immune cell clusters with abnormal phenotypes. In particular, we identified a previously overlooked cancer stem-like cell cluster (ALDH+PD-L1+ER-β−) that was strongly associated with poor prognosis. We elucidated the different spatial architectures of immune cells (excluded, infiltrated, and deserted) and tumor-associated collagens (curved, stretched, directionally distributed, and chaotic) in the MIBC TME. The present study is the first to provide in-depth insight into the complexity of the MIBC TME at the single-cell level. Our results will improve the general understanding of the heterogeneous characteristics of MIBC, potentially facilitating patient stratification and personalized therapy.
The Modes of Dysregulation of the Proto-Oncogene T-Cell Leukemia/Lymphoma 1A
Authors: Stachelscheid Johanna , Jiang Qu , Herling Marco
Published: November 2021

Incomplete biological concepts in lymphoid neoplasms still dictate to a large extent the limited availability of efficient targeted treatments, which entertains the mostly unsatisfactory clinical outcomes. Aberrant expression of the embryonal and lymphatic TCL1 family of oncogenes, i.e., the paradigmatic TCL1A, but also TML1 or MTCP1, is causally implicated in T- and B-lymphocyte transformation. TCL1A also carries prognostic information in these particular T-cell and B-cell tumors. More recently, the TCL1A oncogene has been observed also in epithelial tumors as part of oncofetal stemness signatures. Although the concepts on the modes of TCL1A dysregulation in lymphatic neoplasms and solid tumors are still incomplete, there are recent advances in defining the mechanisms of its (de)regulation. This review presents a comprehensive overview of TCL1A expression in tumors and the current understanding of its (dys)regulation via genomic aberrations, epigenetic modifications, or deregulation of TCL1A-targeting micro RNAs. We also summarize triggers that act through such transcriptional and translational regulation, i.e., altered signals by the tumor microenvironment. A refined mechanistic understanding of these modes of dysregulations together with improved concepts of TCL1A-associated malignant transformation can benefit future approaches to specifically interfere in TCL1A-initiated or -driven tumorigenesis.
The Role of HGF/MET Signaling in Metastatic Uveal Melanoma
Authors: Tanaka Ryota , Terai Mizue , Londin Eric , Sato Takami
Published: November 2021

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit in MUM patients, it is important to understand how MET signaling drives cellular functions in uveal melanoma cells. Here, we review the HGF/MET signaling biology and the role of HGF/MET blockades in uveal melanoma.
Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres
Authors: Roosen Joey , Arntz Mark J. , Janssen Marcel J. R. , de Jong Sytse F. , Fütterer Jurgen J. , Overduin Christiaan G. , Nijsen J. Frank W.
Published: November 2021

Selective internal radiation therapy (SIRT) is a treatment modality for liver tumours during which radioactive microspheres are injected into the hepatic arterial tree. Holmium-166 (166Ho) microspheres used for SIRT can be visualized and quantified with MRI, potentially allowing for MRI guidance during SIRT. The purpose of this study was to investigate the MRI compatibility of two angiography catheters and a microcatheter typically used for SIRT, and to explore the detectability of 166Ho microspheres in a flow phantom using near real-time MRI. MR safety tests were performed at a 3 T MRI system according to American Society for Testing of Materials standard test methods. To assess the near real-time detectability of 166Ho microspheres, a flow phantom was placed in the MRI bore and perfused using a peristaltic pump, simulating the flow in the hepatic artery. Dynamic MR imaging was performed using a 2D FLASH sequence during injection of different concentrations of 166Ho microspheres. In the safety assessment, no significant heating (ΔTmax 0.7 °C) was found in any catheter, and no magnetic interaction was found in two out of three of the used catheters. Near real-time MRI visualization of 166Ho microsphere administration was feasible and depended on holmium concentration and vascular flow speed. Finally, we demonstrate preliminary imaging examples on the in vivo catheter visibility and near real-time imaging during 166Ho microsphere administration in an initial patient case treated with SIRT in a clinical 3 T MRI. These results support additional research to establish the feasibility and safety of this procedure in vivo and enable the further development of a personalized MRI-guided approach to SIRT.
Machine Learning Based on Morphological Features Enables Classification of Primary Intestinal T-Cell Lymphomas
Authors: Yu Wei-Hsiang , Li Chih-Hao , Wang Ren-Ching , Yeh Chao-Yuan , Chuang Shih-Sung
Published: November 2021

The aim of this study was to investigate the feasibility of using machine learning techniques based on morphological features in classifying two subtypes of primary intestinal T-cell lymphomas (PITLs) defined according to the WHO criteria: monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) versus intestinal T-cell lymphoma, not otherwise specified (ITCL-NOS), which is considered a major challenge for pathological diagnosis. A total of 40 histopathological whole-slide images (WSIs) from 40 surgically resected PITL cases were used as the dataset for model training and testing. A deep neural network was trained to detect and segment the nuclei of lymphocytes. Quantitative nuclear morphometrics were further computed from these predicted contours. A decision-tree-based machine learning algorithm, XGBoost, was then trained to classify PITL cases into two disease subtypes using these nuclear morphometric features. The deep neural network achieved an average precision of 0.881 in the cell segmentation work. In terms of classifying MEITL versus ITCL-NOS, the XGBoost model achieved an area under receiver operating characteristic curve (AUC) of 0.966. Our research demonstrated an accurate, human-interpretable approach to using machine learning algorithms for reducing the high dimensionality of image features and classifying T cell lymphomas that present challenges in morphologic diagnosis. The quantitative nuclear morphometric features may lead to further discoveries concerning the relationship between cellular phenotype and disease status.
The Role of Skin Tests in the Prevention and Diagnosis of Hypersensitivity Reactions to Platinum Agents in Gynecological Cancer: A Single-Center Italian Retrospective Study
Authors: Puxeddu Ilaria , Petrelli Fiorella , Guerrieri Maria Elena , Cosio Stefania , Del Corso Isabella , Rocchi Valeria , Manca Maria Laura , Migliorini Paola , Gadducci Angiolo
Published: November 2021

Background: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs. Methods: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure. Results: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients. Conclusions: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents.